Trial Outcomes & Findings for A Phase 2 Study to Evaluate the Safety, Efficacy, Pharmacokinetics and Pharmacodynamics of PF-06252616 in Duchenne Muscular Dystrophy (NCT NCT02310763)

NCT ID: NCT02310763

Last Updated: 2020-12-07

Results Overview

An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. A serious adverse event (SAE) was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. AEs included both SAEs and AEs. TEAEs were AEs occurred following the start of treatment or AEs increasing in severity during treatment. Severe TEAEs were TEAEs that interfered significantly with participants' usual function. Treatment-related TEAEs were determined by the investigator.

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 121 participants
• Primary outcome timeframe: Study Day 1 to Week 49 visit
• Results posted on: 2020-12-07

Participant Flow

A total of 162 participants were screened, 121 participants were enrolled in the study and assigned to 1 of 3 sequences. Only 120 participants received the study treatment and 1 participant withdrew prior to dosing.

Participant milestones

Measure	Sequence 1 Participants in this sequence received domagrozumab in a dose escalating fashion (5, 20 and 40 mg/kg) for 48 weeks (Period 1). At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). From Week 49 (Period 2), participants continued to receive domagrozumab at the maximum tolerated dose (40 mg/kg) every 4 weeks for additional 48 weeks or until early termination of the study.	Sequence 2 Participants in this sequence received domagrozumab in a dose escalating fashion (5, 20 and 40mg/kg) for 48 weeks (Period 1). At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). From Week 49 (Period 2), participants received placebo for additional 48 weeks or until early termination of the study.	Sequence 3 Participants in this sequence received placebo for 48 weeks (Period 1). From Week 49 (Period 2), participants received domagrozumab in a dose escalating fashion (5, 20 and 40 mg/kg) for additional 48 weeks or until early termination of the study. At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses).
Period 1 (Weeks 1 to 48) STARTED	41	39	40
Period 1 (Weeks 1 to 48) COMPLETED	38	37	38
Period 1 (Weeks 1 to 48) NOT COMPLETED	3	2	2
Period 2 (Weeks 49 to 96) STARTED	38	37	38
Period 2 (Weeks 49 to 96) COMPLETED	22	21	22
Period 2 (Weeks 49 to 96) NOT COMPLETED	16	16	16

Reasons for withdrawal

Measure	Sequence 1 Participants in this sequence received domagrozumab in a dose escalating fashion (5, 20 and 40 mg/kg) for 48 weeks (Period 1). At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). From Week 49 (Period 2), participants continued to receive domagrozumab at the maximum tolerated dose (40 mg/kg) every 4 weeks for additional 48 weeks or until early termination of the study.	Sequence 2 Participants in this sequence received domagrozumab in a dose escalating fashion (5, 20 and 40mg/kg) for 48 weeks (Period 1). At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). From Week 49 (Period 2), participants received placebo for additional 48 weeks or until early termination of the study.	Sequence 3 Participants in this sequence received placebo for 48 weeks (Period 1). From Week 49 (Period 2), participants received domagrozumab in a dose escalating fashion (5, 20 and 40 mg/kg) for additional 48 weeks or until early termination of the study. At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses).
Period 1 (Weeks 1 to 48) Withdrawal by Subject	1	1	1
Period 1 (Weeks 1 to 48) Unable to comply with study procedures	0	1	1
Period 1 (Weeks 1 to 48) Lost to Follow-up	1	0	0
Period 1 (Weeks 1 to 48) Adverse Event	1	0	0
Period 2 (Weeks 49 to 96) Study terminated by sponsor	16	16	16

Baseline Characteristics

A Phase 2 Study to Evaluate the Safety, Efficacy, Pharmacokinetics and Pharmacodynamics of PF-06252616 in Duchenne Muscular Dystrophy

Baseline characteristics by cohort

Measure	Sequence 1 n=41 Participants Participants in this sequence received domagrozumab in a dose escalating fashion (5, 20 and 40 mg/kg) for 48 weeks (Period 1). At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). From Week 49 (Period 2), participants continued to receive domagrozumab at the maximum tolerated dose (40 mg/kg) every 4 weeks for additional 48 weeks or until early termination of the study.	Sequence 2 n=39 Participants Participants in this sequence received domagrozumab in a dose escalating fashion (5, 20 and 40mg/kg) for 48 weeks (Period 1). At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses). From Week 49 (Period 2), participants received placebo for additional 48 weeks or until early termination of the study.	Sequence 3 n=40 Participants Participants in this sequence received placebo for 48 weeks (Period 1). From Week 49 (Period 2), participants received domagrozumab in a dose escalating fashion (5, 20 and 40 mg/kg) for additional 48 weeks or until early termination of the study. At each dose level, dosing was administered over 2 hours by intravenous infusion every 4 weeks for a total of 16 weeks (4 doses).	Total n=120 Participants Total of all reporting groups
Age, Categorical <=18 years	41 Participants n=5 Participants	39 Participants n=7 Participants	40 Participants n=5 Participants	120 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Continuous	8.3 Years STANDARD_DEVIATION 1.9 • n=5 Participants	8.5 Years STANDARD_DEVIATION 1.5 • n=7 Participants	9.3 Years STANDARD_DEVIATION 2.3 • n=5 Participants	8.7 Years STANDARD_DEVIATION 2.0 • n=4 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Sex: Female, Male Male	41 Participants n=5 Participants	39 Participants n=7 Participants	40 Participants n=5 Participants	120 Participants n=4 Participants
Race/Ethnicity, Customized White	33 Participants n=5 Participants	33 Participants n=7 Participants	35 Participants n=5 Participants	101 Participants n=4 Participants
Race/Ethnicity, Customized Black	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Race/Ethnicity, Customized Asian	6 Participants n=5 Participants	5 Participants n=7 Participants	4 Participants n=5 Participants	15 Participants n=4 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants

PRIMARY outcome

Timeframe: Study Day 1 to Week 49 visit

Population: The analysis population included all participants who received at least 1 dose of investigational drug. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure.

An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. A serious adverse event (SAE) was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. AEs included both SAEs and AEs. TEAEs were AEs occurred following the start of treatment or AEs increasing in severity during treatment. Severe TEAEs were TEAEs that interfered significantly with participants' usual function. Treatment-related TEAEs were determined by the investigator.

Outcome measures

Measure	Placebo n=40 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg n=80 Participants Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg n=78 Participants Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg n=76 Participants Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Week 49 All-causalities TEAE	38 Participants	66 Participants	57 Participants	59 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Week 49 Treatment-related TEAE	14 Participants	18 Participants	14 Participants	16 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Week 49 All-causalities serious TEAE	0 Participants	1 Participants	1 Participants	1 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Week 49 Treatment-related serious TEAE	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Week 49 All-causalities severe TEAE	2 Participants	2 Participants	3 Participants	2 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Week 49 Treatment-related severe TEAE	0 Participants	0 Participants	0 Participants	1 Participants

PRIMARY outcome

Timeframe: Study Day 1 to Week 49 visit

Population: The analysis population included all participants who received at least 1 dose of investigational drug. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure.

An AE was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. TEAEs were AEs occurred following the start of treatment or AEs increasing in severity during treatment. Treatment-related TEAEs were determined by the investigator.

Outcome measures

Measure	Placebo n=40 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg n=80 Participants Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg n=78 Participants Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg n=76 Participants Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Number of Participants Who Discontinued From the Study Due to TEAEs by Week 49 All-causalities TEAE	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants Who Discontinued From the Study Due to TEAEs by Week 49 Treatment-related TEAE	0 Participants	0 Participants	0 Participants	1 Participants

PRIMARY outcome

Timeframe: Study Day 1 to Week 49 visit

Population: The analysis population included all participants who received at least 1 dose of investigational drug. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure.

An AE was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. TEAEs were AEs occurred following the start of treatment or AEs increasing in severity during treatment. Treatment-related TEAEs were determined by the investigator.

Outcome measures

Measure	Placebo n=40 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg n=80 Participants Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg n=78 Participants Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg n=76 Participants Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Number of Participants With Dose Reduced or Temporary Discontinuation Due to TEAEs by Week 49 Treatment-related TEAE	3 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Dose Reduced or Temporary Discontinuation Due to TEAEs by Week 49 All-causalities TEAE	8 Participants	4 Participants	4 Participants	0 Participants

PRIMARY outcome

Timeframe: Baseline to Week 49 visit

Population: This analysis population included all participants who received at least 1 dose of investigational drug. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.

Hematology evaluation included: hemoglobin, hematocrit, red blood cell (RBC) count, platelets, RBC morphology, white blood cell (WBC) count, absolute lymphocytes, absolute atypical lymphocytes, absolute total neutrophils, absolute total neutrophils count, absolute band cells, absolute basophils, absolute eosinophils, absolute monocytes and absolute myelocytes.

Outcome measures

Measure	Placebo n=40 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg n=80 Participants Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg n=78 Participants Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg n=76 Participants Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology Absolute basophils >1.2*ULN	2 Participants	1 Participants	1 Participants	2 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology Absolute eosinophils >1.2*ULN	6 Participants	2 Participants	6 Participants	6 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology Absolute monocytes >1.2*ULN	1 Participants	1 Participants	2 Participants	2 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology RBC count <0.8*LLN	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology Platelets <0.5*LLN	1 Participants	1 Participants	1 Participants	1 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology Platelets >1.75*upper limit of normal (ULN)	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology Absolute atypical lymphocytes >0 (10*3/uL)	—	1 Participants	—	1 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology Absolute total neutrophils <0.8*LLN	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology Absolute total neutrophils >1.2*ULN	13 Participants	8 Participants	5 Participants	5 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology Absolute total neutrophils count >8.15 (10*3/uL)	20 Participants	13 Participants	12 Participants	9 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology Absolute band cells >0.27 (10*3/uL)	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology Hemoglobin <0.8*lower limit of normal (LLN)	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology Hematocrit <0.8*LLN	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology Absolute lymphocytes >1.2*ULN	1 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology RBC Morphology >0	0 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology WBC count <0.6*LLN	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology WBC count >1.5*ULN	0 Participants	1 Participants	1 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology Absolute Lymphocytes <0.8*LLN	0 Participants	2 Participants	2 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology Absolute total neutrophils count <1.35 (10*3/uL)	2 Participants	0 Participants	2 Participants	1 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hematology Absolute myelocytes >0 (10*3/uL)	—	—	—	1 Participants

PRIMARY outcome

Timeframe: Baseline to Week 49 visit

Population: This analysis population included all participants who received at least 1 dose of investigational drug. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure.

Coagulation evaluation included activated partial thromboplastin time (aPTT) and prothrombin time (PT).

Outcome measures

Measure	Placebo n=40 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg n=80 Participants Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg n=78 Participants Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg n=76 Participants Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Coagulation PT >1.1*ULN	13 Participants	6 Participants	3 Participants	7 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Coagulation aPTT >1.1*ULN	1 Participants	1 Participants	1 Participants	2 Participants

PRIMARY outcome

Timeframe: Baseline to Week 49 visit

Population: This analysis population included all participants who received at least 1 dose of investigational drug. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.

Liver function evaluation included: total/direct/indirect bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), alkaline phosphatase, total protein, albumin and glutamate dehydrogenase.

Outcome measures

Measure	Placebo n=40 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg n=80 Participants Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg n=78 Participants Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg n=76 Participants Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Liver Function Direct bilirubin >1.5*ULN	0 Participants	—	—	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Liver Function AST >3*ULN	39 Participants	80 Participants	76 Participants	74 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Liver Function ALT >3*ULN	40 Participants	80 Participants	78 Participants	75 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Liver Function Alkaline phosphatase >3*ULN	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Liver Function Total protein <0.8*LLN	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Liver Function Total bilirubin >1.5*ULN	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Liver Function Indirect bilirubin >1.5*ULN	0 Participants	—	—	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Liver Function GGT >3*ULN	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Liver Function Total protein >1.2*ULN	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Liver Function Albumin <0.8*LLN	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Liver Function Albumin >1.2*ULN	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Liver Function Glutamate dehydrogenase >1.0*ULN	8 Participants	8 Participants	6 Participants	5 Participants

PRIMARY outcome

Timeframe: Baseline to Week 49 visit

Population: This analysis population included all participants who received at least 1 dose of investigational drug. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure.

Renal function evaluation included: blood urea nitrogen (BUN), creatinine and uric acid.

Outcome measures

Measure	Placebo n=40 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg n=80 Participants Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg n=78 Participants Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg n=76 Participants Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Renal Function Uric acid >1.2*ULN	0 Participants	1 Participants	3 Participants	3 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Renal Function BUN >1.3*ULN	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Renal Function Creatinine >1.3*ULN	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Baseline to Week 49 visit

Population: This analysis population included all participants who received at least 1 dose of investigational drug. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.

Electrolytes evaluation included: sodium, potassium, chloride, calcium, phosphate, bicarbonate, ferritin, transferrin saturation, iron, iron binding capacity and unsaturated iron binding capacity. Number of participants with iron abnormalities was reported in different age groups.

Outcome measures

Measure	Placebo n=40 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg n=80 Participants Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg n=78 Participants Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg n=76 Participants Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes Sodium <0.95*LLN	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes Potassium >1.1*ULN	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes Chloride >1.1*ULN	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes Phosphate <0.8*LLN	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes Phosphate >1.2*ULN	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes Iron (11 Years<=Age<18 Years) <50 (ug/dL)	2 Participants	4 Participants	2 Participants	2 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes Iron (11 Years<=Age<18 Years) >170 (ug/dL)	0 Participants	1 Participants	1 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes Transferrin saturation >50%	4 Participants	9 Participants	19 Participants	18 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes Sodium >1.05*ULN	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes Potassium <0.9*LLN	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes Chloride <0.9*LLN	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes Calcium <0.9*LLN	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes Calcium >1.1*ULN	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes Bicarbonate <0.9*LLN	8 Participants	2 Participants	3 Participants	4 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes Bicarbonate >1.1*ULN	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes Iron (1 Year<=Age<11 Years) <50 (ug/dL)	19 Participants	23 Participants	14 Participants	11 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes Iron (1 Year<=Age<11 Years) >120 (ug/dL)	12 Participants	29 Participants	33 Participants	39 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes Ferritin <15 (ug/L)	20 Participants	32 Participants	38 Participants	42 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes Ferritin >140 (ug/L)	1 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes Iron binding capacity <37.6 (ug/dL)	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes Unsaturated iron binding capacity<130 (ug/dL)	3 Participants	7 Participants	6 Participants	10 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes Unsaturated iron binding capacity >375 (ug/dL)	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Electrolytes Transferrin saturation <20%	26 Participants	34 Participants	26 Participants	20 Participants

PRIMARY outcome

Timeframe: Baseline to Week 49 visit

Population: This analysis population included all participants who received at least 1 dose of investigational drug. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.

Hormone evaluations included free thyroxine (T4), thyroid stimulating hormone (TSH), lutenizing hormone (LH), follicle stimulating hormone (FSH), and androstenedione. Numbers of participants with abnormalities of LH, FSH and androstenedione were reported in different age groups.

Outcome measures

Measure	Placebo n=40 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg n=80 Participants Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg n=78 Participants Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg n=76 Participants Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones TSH >1.2*ULN	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones LH (15 Days<=Age<7 Years) >2.8 (mIU/mL)	0 Participants	0 Participants	0 Participants	—
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones Androstenedione (12Years<=Age<14Years)<11 (ng/dL)	3 Participants	4 Participants	2 Participants	2 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones Androstenedione(12 Years<=Age<14Years)>64 (ng/dL)	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones LH (7 Years<=Age<9 Years) <0.3 (mIU/mL)	6 Participants	23 Participants	21 Participants	14 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones Free T4 <0.8*LLN	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones Free T4 >1.2*ULN	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones TSH <0.8*LLN	0 Participants	2 Participants	0 Participants	1 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones LH (15 Days<=Age<7 Years) <0.3 (mIU/mL)	1 Participants	2 Participants	0 Participants	—
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones LH (7 Years<=Age<9 Years) >2.8 (mIU/mL)	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones LH (9 Years<=Age<11 Years) <0.3 (mIU/mL)	17 Participants	17 Participants	23 Participants	27 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones LH (9 Years<=Age<11 Years) >2.8 (mIU/mL)	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones LH (11 Years<=Age<12 Years) <0.3 (mIU/mL)	2 Participants	2 Participants	3 Participants	1 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones LH (11 Years<=Age<12 Years) >1.8 (mIU/mL)	1 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones LH (12 Years<=Age<13 Years) <0.3 (mIU/mL)	1 Participants	1 Participants	2 Participants	2 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones LH (12 Years<=Age<13 Years) >4.0 (mIU/mL)	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones LH (13 Years<=Age<14 Years) <0.3 (mIU/mL)	3 Participants	1 Participants	0 Participants	1 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones LH (13 Years<=Age<14 Years) >6.0 (mIU/mL)	0 Participants	1 Participants	1 Participants	1 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones FSH (4 Years<=Age<7 Years) >6.70 (mIU/mL)	0 Participants	0 Participants	0 Participants	—
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones FSH (7 Years<=Age<9 Years) >4.10 (mIU/mL)	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones FSH (9 Years<=Age<11 Years) >4.50 (mIU/mL)	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones FSH (11 Years<=Age<12 Years) <0.40 (mIU/mL)	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones FSH (11 Years<=Age<12 Years) >8.90 (mIU/mL)	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones FSH (12 Years<=Age<13 Years) <0.50 (mIU/mL)	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones FSH (12 Years<=Age<13 Years) >10.50 (mIU/mL)	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones FSH (13 Years<=Age<14 Years) <0.70 (mIU/mL)	0 Participants	1 Participants	0 Participants	2 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones FSH (13 Years<=Age<14 Years) >10.80 (mIU/mL)	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones Androstenedione (1 Year<=Age<7 Years) <8 (ng/dL)	1 Participants	2 Participants	1 Participants	—
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones Androstenedione (1 Year<=Age<7Years) >50(ng/dL)	0 Participants	0 Participants	0 Participants	—
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones Androstenedione (7 Years<=Age<10Years)<3(ng/dL)	5 Participants	11 Participants	10 Participants	7 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones Androstenedione(7Years<=Age<10Years) >31(ng/dL)	1 Participants	0 Participants	4 Participants	4 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones Androstenedione(10Years<=Age<12Years) <7(ng/dL)	13 Participants	8 Participants	8 Participants	10 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Hormones Androstenedione (10Years<=Age<12Years)>41 (ng/dL)	3 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Baseline to Week 49 visit

Population: This analysis population included all participants who received at least 1 dose of investigational drug. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.

Clinical chemistry evaluation included glucose, creatine kinase (CK), troponin I, and amylase.

Outcome measures

Measure	Placebo n=40 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg n=80 Participants Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg n=78 Participants Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg n=76 Participants Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Clinical Chemistry Glucose <0.6*LLN	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Clinical Chemistry Glucose >1.5*ULN	0 Participants	1 Participants	0 Participants	2 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Clinical Chemistry CK >2.0*ULN	40 Participants	80 Participants	78 Participants	76 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Clinical Chemistry Troponin I >3.0*ULN	11 Participants	12 Participants	10 Participants	13 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Clinical Chemistry Amylase >1.5*ULN	0 Participants	0 Participants	0 Participants	1 Participants

PRIMARY outcome

Timeframe: Baseline to Week 49 visit

Population: This analysis population included all participants who received at least 1 dose of investigational drug. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.

Urinalysis included: urine pH, qualitative urine glucose, qualitative urine ketones, qualitative urine protein, qualitative blood/hemoglobin, urine nitrite, urine leukocytes, urine RBC, urine WBC, urine granular casts, urine hyaline casts, urine urate (uric acid) acidic crystal, urine calcium oxalate crystals, urine amorphous crystals, urine bacteria, urine microscopic exam.

Outcome measures

Measure	Placebo n=40 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg n=80 Participants Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg n=78 Participants Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg n=76 Participants Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis Qualitative urine glucose (dipstick) >=1	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis Qualitative urine ketones(dipstick) >=1	3 Participants	3 Participants	5 Participants	6 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis Qualitative urine protein (dipstick) >=1	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis Qualitative urine blood/hemoglobin (dipstick) >=1	0 Participants	2 Participants	1 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis Urine nitrite (dipstick) >=1	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis Urine leukocytes (dipstick): +1	0 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis Urine RBC >=20 (/high power field[HPF])	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis Urine WBC >=20 (/HPF)	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis Urine granular casts >1 (/low power field [LPF])	1 Participants	—	—	—
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis Urine hyaline casts >1 (/LPF)	2 Participants	—	—	—
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis Urine urate (uric acid) acidic crystal: Present	4 Participants	2 Participants	2 Participants	2 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis Urine calcium oxalate crystals: Present	19 Participants	24 Participants	23 Participants	24 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis Urine amorphous crystals: Present	7 Participants	7 Participants	6 Participants	11 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis Urine bacteria >20 (/HPF)	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis Urine microscopic exam: Positive	31 Participants	50 Participants	49 Participants	45 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis Urine pH (dipstick) <4.5	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Urinalysis Urine pH (dipstick) >8	0 Participants	1 Participants	1 Participants	1 Participants

PRIMARY outcome

Timeframe: Baseline to Week 49 visit

Population: This analysis population included all participants who received at least 1 dose of investigational drug and had at least 1 fecal evaluation.

Number of participants with blood detected in fecal samples is presented.

Outcome measures

Measure	Placebo n=40 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg n=79 Participants Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg n=78 Participants Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg n=74 Participants Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) by Week 49 - Fecal	2 Participants	8 Participants	2 Participants	3 Participants

PRIMARY outcome

Timeframe: Screening, Weeks 13, 29 and 45

Population: This analysis population included all participants who received at least 1 dose of investigational drug. Number analyzed refers to number of participants evaluable for specified rows of categories.

Magnetic resonance imaging (MRI) of Liver was obtained to quantify liver iron accumulation for safety monitoring. MRIs were sent to an independent central radiology imaging facility for calculation of the average transverse relaxation rate (R2*) value which was used to monitor for iron accumulation in the liver. Number of participants meeting the following criteria is presented as follows: 1) normal: R2*<=75Hz at 1.5T or <=139 Hz at 3.0T; 2) above normal: R2*>75Hz and <=190Hz at 1.5T or R2* >139Hz and <=369Hz at 3.0T; 3) mild overload: R2*>190Hz at 1.5T or R2*>360Hz at 3.0T.

Outcome measures

Measure	Placebo n=41 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg n=39 Participants Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg n=40 Participants Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Categorical Summary of Liver Iron Accumulation by Week 49 Normal, Screening	41 Participants	39 Participants	40 Participants	—
Categorical Summary of Liver Iron Accumulation by Week 49 Above normal, Screening	0 Participants	0 Participants	0 Participants	—
Categorical Summary of Liver Iron Accumulation by Week 49 Mild overload, Screening	0 Participants	0 Participants	0 Participants	—
Categorical Summary of Liver Iron Accumulation by Week 49 Normal, Week 13	27 Participants	24 Participants	26 Participants	—
Categorical Summary of Liver Iron Accumulation by Week 49 Above normal, Week 13	0 Participants	0 Participants	0 Participants	—
Categorical Summary of Liver Iron Accumulation by Week 49 Mild overload, Week 13	0 Participants	0 Participants	0 Participants	—
Categorical Summary of Liver Iron Accumulation by Week 49 Normal, Week 29	23 Participants	21 Participants	21 Participants	—
Categorical Summary of Liver Iron Accumulation by Week 49 Above normal, Week 29	0 Participants	0 Participants	0 Participants	—
Categorical Summary of Liver Iron Accumulation by Week 49 Mild overload, Week 29	0 Participants	0 Participants	0 Participants	—
Categorical Summary of Liver Iron Accumulation by Week 49 Normal, Week 45	37 Participants	37 Participants	38 Participants	—
Categorical Summary of Liver Iron Accumulation by Week 49 Above normal, Week 45	0 Participants	0 Participants	0 Participants	—
Categorical Summary of Liver Iron Accumulation by Week 49 Mild overload, Week 45	0 Participants	0 Participants	0 Participants	—

PRIMARY outcome

Timeframe: Baseline to Week 49 visit

Population: This analysis population included all participants who received at least 1 dose of investigational drug.

Physical examination included head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems. A targeted nose and throat mucosal exam were also performed to monitor for any signs of mucosal telangiectasias. An SAE was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. Investigators determined which physical examination findings were reported as SAEs.

Outcome measures

Measure	Placebo n=41 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg n=39 Participants Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg n=40 Participants Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Number of Participants With Physical Examination Findings Reported as SAEs by Week 49	0 Participants	0 Participants	0 Participants	—

PRIMARY outcome

Timeframe: Baseline, Weeks 17, 33 and 49

Population: This analysis population included all participants who received at least 1 dose of investigational drug. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.

Tanner staging was performed before the first dose of each dose escalation to monitor for signs of accelerated sexual development. The physical changes in pubertal development (pubic hair, penis and testes) were assessed using the system described by Marshall and Tanner. Stage 1 is preadolescent, Stages 2, 3, and 4 are initiation of puberty and Stage 5 is mature adult. Details about the system can be referred to Tanner JM. Growth at Adolescence. Blackwell Scientific Publications 1962; 2nd edition.

Outcome measures

Measure	Placebo n=40 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg n=80 Participants Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Summary of Tanner Stage Rating by Week 49 Pubic hair, Stage 4, Week 49	1 Participants	1 Participants	—	—
Summary of Tanner Stage Rating by Week 49 Pubic hair, Stage 5, Week 49	1 Participants	0 Participants	—	—
Summary of Tanner Stage Rating by Week 49 Penis, Stage 1, Baseline	30 Participants	70 Participants	—	—
Summary of Tanner Stage Rating by Week 49 Pubic hair, Stage 1, Baseline	35 Participants	70 Participants	—	—
Summary of Tanner Stage Rating by Week 49 Pubic hair, Stage 2, Baseline	4 Participants	7 Participants	—	—
Summary of Tanner Stage Rating by Week 49 Pubic hair, Stage 3, Baseline	0 Participants	1 Participants	—	—
Summary of Tanner Stage Rating by Week 49 Pubic hair, Stage 4, Baseline	1 Participants	0 Participants	—	—
Summary of Tanner Stage Rating by Week 49 Pubic hair, Stage 5, Baseline	0 Participants	0 Participants	—	—
Summary of Tanner Stage Rating by Week 49 Pubic hair, Stage 1, Week 17	30 Participants	64 Participants	—	—
Summary of Tanner Stage Rating by Week 49 Pubic hair, Stage 2, Week 17	9 Participants	11 Participants	—	—
Summary of Tanner Stage Rating by Week 49 Pubic hair, Stage 3, Week 17	0 Participants	2 Participants	—	—
Summary of Tanner Stage Rating by Week 49 Pubic hair, Stage 4, Week 17	1 Participants	0 Participants	—	—
Summary of Tanner Stage Rating by Week 49 Pubic hair, Stage 5, Week 17	0 Participants	0 Participants	—	—
Summary of Tanner Stage Rating by Week 49 Pubic hair, Stage 1, Week 33	23 Participants	60 Participants	—	—
Summary of Tanner Stage Rating by Week 49 Pubic hair, Stage 2, Week 33	11 Participants	13 Participants	—	—
Summary of Tanner Stage Rating by Week 49 Pubic hair, Stage 3, Week 33	1 Participants	1 Participants	—	—
Summary of Tanner Stage Rating by Week 49 Pubic hair, Stage 4, Week 33	1 Participants	1 Participants	—	—
Summary of Tanner Stage Rating by Week 49 Pubic hair, Stage 5, Week 33	0 Participants	0 Participants	—	—
Summary of Tanner Stage Rating by Week 49 Pubic hair, Stage 1, Week 49	21 Participants	52 Participants	—	—
Summary of Tanner Stage Rating by Week 49 Pubic hair, Stage 2, Week 49	11 Participants	15 Participants	—	—
Summary of Tanner Stage Rating by Week 49 Pubic hair, Stage 3, Week 49	3 Participants	4 Participants	—	—
Summary of Tanner Stage Rating by Week 49 Penis, Stage 2, Baseline	9 Participants	7 Participants	—	—
Summary of Tanner Stage Rating by Week 49 Penis, Stage 3, Baseline	0 Participants	1 Participants	—	—
Summary of Tanner Stage Rating by Week 49 Penis, Stage 4, Baseline	1 Participants	0 Participants	—	—
Summary of Tanner Stage Rating by Week 49 Penis, Stage 5, Baseline	0 Participants	0 Participants	—	—
Summary of Tanner Stage Rating by Week 49 Penis, Stage 1, Week 17	29 Participants	68 Participants	—	—
Summary of Tanner Stage Rating by Week 49 Penis, Stage 2, Week 17	10 Participants	8 Participants	—	—
Summary of Tanner Stage Rating by Week 49 Penis, Stage 3, Week 17	0 Participants	1 Participants	—	—
Summary of Tanner Stage Rating by Week 49 Penis, Stage 4, Week 17	1 Participants	0 Participants	—	—
Summary of Tanner Stage Rating by Week 49 Penis, Stage 5, Week 17	0 Participants	0 Participants	—	—
Summary of Tanner Stage Rating by Week 49 Penis, Stage 1, Week 33	22 Participants	58 Participants	—	—
Summary of Tanner Stage Rating by Week 49 Penis, Stage 2, Week 33	11 Participants	16 Participants	—	—
Summary of Tanner Stage Rating by Week 49 Penis, Stage 3, Week 33	3 Participants	1 Participants	—	—
Summary of Tanner Stage Rating by Week 49 Penis, Stage 4, Week 33	0 Participants	0 Participants	—	—
Summary of Tanner Stage Rating by Week 49 Penis, Stage 5, Week 33	0 Participants	0 Participants	—	—
Summary of Tanner Stage Rating by Week 49 Penis, Stage 1, Week 49	21 Participants	57 Participants	—	—
Summary of Tanner Stage Rating by Week 49 Penis, Stage 2, Week 49	9 Participants	14 Participants	—	—
Summary of Tanner Stage Rating by Week 49 Penis, Stage 3, Week 49	5 Participants	1 Participants	—	—
Summary of Tanner Stage Rating by Week 49 Penis, Stage 4, Week 49	2 Participants	0 Participants	—	—
Summary of Tanner Stage Rating by Week 49 Penis, Stage 5, Week 49	0 Participants	0 Participants	—	—
Summary of Tanner Stage Rating by Week 49 Testes, Stage 1, Baseline	34 Participants	67 Participants	—	—
Summary of Tanner Stage Rating by Week 49 Testes, Stage 2, Baseline	4 Participants	10 Participants	—	—
Summary of Tanner Stage Rating by Week 49 Testes, Stage 3, Baseline	1 Participants	1 Participants	—	—
Summary of Tanner Stage Rating by Week 49 Testes, Stage 4, Baseline	1 Participants	0 Participants	—	—
Summary of Tanner Stage Rating by Week 49 Testes, Stage 5, Baseline	0 Participants	0 Participants	—	—
Summary of Tanner Stage Rating by Week 49 Testes, Stage 1, Week 17	29 Participants	66 Participants	—	—
Summary of Tanner Stage Rating by Week 49 Testes, Stage 2, Week 17	10 Participants	10 Participants	—	—
Summary of Tanner Stage Rating by Week 49 Testes, Stage 3, Week 17	0 Participants	1 Participants	—	—
Summary of Tanner Stage Rating by Week 49 Testes, Stage 4, Week 17	1 Participants	0 Participants	—	—
Summary of Tanner Stage Rating by Week 49 Testes, Stage 5, Week 17	0 Participants	0 Participants	—	—
Summary of Tanner Stage Rating by Week 49 Testes, Stage 1, Week 33	24 Participants	59 Participants	—	—
Summary of Tanner Stage Rating by Week 49 Testes, Stage 2, Week 33	9 Participants	15 Participants	—	—
Summary of Tanner Stage Rating by Week 49 Testes, Stage 3, Week 33	1 Participants	1 Participants	—	—
Summary of Tanner Stage Rating by Week 49 Testes, Stage 4, Week 33	2 Participants	0 Participants	—	—
Summary of Tanner Stage Rating by Week 49 Testes, Stage 5, Week 33	0 Participants	0 Participants	—	—
Summary of Tanner Stage Rating by Week 49 Testes, Stage 1, Week 49	19 Participants	53 Participants	—	—
Summary of Tanner Stage Rating by Week 49 Testes, Stage 2, Week 49	11 Participants	15 Participants	—	—
Summary of Tanner Stage Rating by Week 49 Testes, Stage 3, Week 49	4 Participants	3 Participants	—	—
Summary of Tanner Stage Rating by Week 49 Testes, Stage 4, Week 49	3 Participants	0 Participants	—	—
Summary of Tanner Stage Rating by Week 49 Testes, Stage 5, Week 49	0 Participants	0 Participants	—	—

PRIMARY outcome

Timeframe: Baseline to Week 49 visit

Population: This analysis population included all participants who received at least 1 dose of investigational drug. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure.

Vital signs evaluation included supine systolic and diastolic blood pressure (BP), pulse rate, and respiratory rate. An SAE was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. Investigators determined which vital signs findings were reported as SAEs.

Outcome measures

Measure	Placebo n=40 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg n=80 Participants Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Number of Participants With Vital Signs Findings Reported as SAEs by Week 49	0 Participants	0 Participants	—	—

PRIMARY outcome

Timeframe: Baseline to Week 49 visit

Population: This analysis population included all participants who received at least 1 dose of investigational drug. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure.

Number of participants with ECG data meeting the following criteria are presented: 1) corrected QT interval using Fridericia's formula (QTcF interval) <450msec; 2) QTcF interval >=450 and <480msec; 3) QTcF interval >=480 and <500msec; 4) QTcF interval>=500msec; 5) QTcF interval increase from baseline<30msec; 6) QTcF interval increase from baseline >=30 and <60msec; 7) QTcF interval increase from baseline >=60msec.

Outcome measures

Measure	Placebo n=40 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg n=70 Participants Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg n=67 Participants Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg n=69 Participants Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria by Week 49 QTcF interval <450msec	40 Participants	70 Participants	67 Participants	68 Participants
Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria by Week 49 QTcF interval>=450 and <480msec	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria by Week 49 QTcF interval >=480 and <500msec	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria by Week 49 QTcF interval>=500msec	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria by Week 49 QTcF interval increase <30msec	40 Participants	66 Participants	65 Participants	63 Participants
Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria by Week 49 QTcF interval increase >=30 and <60msec	0 Participants	4 Participants	2 Participants	6 Participants
Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria by Week 49 QTcF interval increase >=60msec	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Baseline to Week 49 visit

Population: This analysis population included all participants who received at least 1 dose of investigational drug. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure.

The LVEF was the ratio of blood ejected during systole to blood in the ventricle at the end of diastole. LVEF was measured by cardiac magnetic resonance image (MRI) or echocardiogram. The same method of cardiac imaging was used consistently within a single participant. Cardiac MRIs were read by a central imaging vendor and echocardiograms were read locally at each site. The LVEF values measured by cardiac MRI and echocardiogram are combined in the following presentation. The analysis of covariance (ANCOVA) model was used to analyze the change from baseline for domagrozumab compared to placebo on LVEF. The baseline result, age, use of angiotensin receptor blocker (ARB)/beta blocker/angiotensin converting enzyme (ACE) inhibitor and treatment were included as fixed effects in the model.

Outcome measures

Measure	Placebo n=35 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg n=72 Participants Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) as Compared to Placebo by Week 49	-0.063 Ratio of blood Standard Error 0.8464	-1.356 Ratio of blood Standard Error 0.5620	—	—

PRIMARY outcome

Timeframe: Screening and Week 49

Population: This analysis population included all participants who received at least 1 dose of investigational drug. Number analyzed refers to number of participants evaluable for specified rows of timepoints.

Bone mineral density (BMD) was evaluated by Dual energy X-ray Absorptiometry (DXA). The height adjusted Z-score presented below is the number of standard deviations which compares the BMD of the participant to the average BMD matched for their age, sex and ethnicity. If the Z-score was -2 standard deviations or lower, the result was "below the expected range for age". If the Z-score was above -2 standard deviations, the result was "within the expected range for age".

Outcome measures

Measure	Placebo n=41 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg n=39 Participants Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg n=40 Participants Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Height-adjusted Z-score of Lumbar Spine Bone Mineral Density Over Time by Week 49 Screening	-0.545151 Standard deviations Standard Deviation 1.2845570	-0.622784 Standard deviations Standard Deviation 1.0778788	-0.572650 Standard deviations Standard Deviation 1.0283031	—
Height-adjusted Z-score of Lumbar Spine Bone Mineral Density Over Time by Week 49 Week 49	-0.683750 Standard deviations Standard Deviation 1.0673420	-0.401631 Standard deviations Standard Deviation 1.0758951	-0.489513 Standard deviations Standard Deviation 1.0057285	—

PRIMARY outcome

Timeframe: Screening, Weeks 17, 33 and 49

Population: This analysis population included all participants who received at least 1 dose of investigational drug. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of timepoints.

Bone age assessment was evaluated by the ratio of the bone age to the chronological age using the X rays of the hand and wrist. Ratio of bone age to chronological age was calculated by bone age/chronological age at scan date. Chronological age at scan date was calculated by (scan date-date of birth+1)/365.25.

Outcome measures

Measure	Placebo n=40 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg n=80 Participants Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Bone Age to Chronological Age Ratio by Week 49 Screening	0.809 Ratio Standard Deviation 0.1656	0.762 Ratio Standard Deviation 0.1650	—	—
Bone Age to Chronological Age Ratio by Week 49 Week 17	0.805 Ratio Standard Deviation 0.1567	0.749 Ratio Standard Deviation 0.1654	—	—
Bone Age to Chronological Age Ratio by Week 49 Week 33	0.790 Ratio Standard Deviation 0.1614	0.750 Ratio Standard Deviation 0.1589	—	—
Bone Age to Chronological Age Ratio by Week 49 Week 49	0.770 Ratio Standard Deviation 0.1604	0.761 Ratio Standard Deviation 0.1778	—	—

PRIMARY outcome

Timeframe: Baseline to Week 49 visit

Population: This analysis population included all participants who received at least 1 dose of investigational drug. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure.

An AE was any untoward medical occurrence in a clinical investigation participant administered a product; the event did not need to have a causal relationship with the treatment. The Columbia Suicide Severity Rating Scale (C-SSRS) was performed to identify the risk of suicide ideation or behavior. AEs of suicide ideation or behavior were determined by the investigator.

Outcome measures

Measure	Placebo n=40 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg n=80 Participants Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Number of Participants With Suicidal Ideation and Suicidal Behavior Reported as AEs by Week 49 Suicidal ideation	0 Participants	0 Participants	—	—
Number of Participants With Suicidal Ideation and Suicidal Behavior Reported as AEs by Week 49 Suicidal behavior	0 Participants	0 Participants	—	—

PRIMARY outcome

Timeframe: Baseline, Weeks 17, 33 and 49

Population: This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of timeponts.

The 4SC quantified the time required for a participant to ascend 4 standard steps. Mixed effect model for repeated measures (MMRM) was used to analyze the change from baseline on 4SC for domagrozumab compared to placebo. The baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.

Outcome measures

Measure	Placebo n=40 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg n=80 Participants Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Change From Baseline on the 4 Stair Climb (4SC) as Compared to Placebo at Weeks 17, 33 and 49 Week 17	1.6896 Seconds Standard Error 0.6776	1.6051 Seconds Standard Error 0.4814	—	—
Change From Baseline on the 4 Stair Climb (4SC) as Compared to Placebo at Weeks 17, 33 and 49 Week 33	3.6407 Seconds Standard Error 1.5837	4.2244 Seconds Standard Error 1.1209	—	—
Change From Baseline on the 4 Stair Climb (4SC) as Compared to Placebo at Weeks 17, 33 and 49 Week 49	8.0122 Seconds Standard Error 3.03	8.2835 Seconds Standard Error 2.1507	—	—

SECONDARY outcome

Timeframe: Baseline, Weeks 17, 33 and 49

Population: This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of timepoints.

FVC was measured by spirometry to evaluate respiratory muscle function. MMRM was used to analyze the change from baseline on FVC for domagrozumab compared to placebo. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.

Outcome measures

Measure	Placebo n=40 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg n=80 Participants Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Change From Baseline as Compared to Placebo on Forced Vital Capacity (FVC) at Weeks 17, 33 and 49 Week 17	0.0578 Liters Standard Error 0.0327	0.0578 Liters Standard Error 0.0250	—	—
Change From Baseline as Compared to Placebo on Forced Vital Capacity (FVC) at Weeks 17, 33 and 49 Week 33	0.1008 Liters Standard Error 0.0385	0.0749 Liters Standard Error 0.0286	—	—
Change From Baseline as Compared to Placebo on Forced Vital Capacity (FVC) at Weeks 17, 33 and 49 Week 49	0.1513 Liters Standard Error 0.0367	0.1092 Liters Standard Error 0.0278	—	—

SECONDARY outcome

Timeframe: Baseline, Weeks 17, 33 and 49

Population: This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of timepoints.

The NSAA is a 17-item test that measured gross motor function. Each individual item received a score of 0-unable to perform independently, 1-able to perform with assistance, or 2-able to perform without assistance. A total score was achieved by summing all the individual items. The total score could range from 0 to 34 (fully-independent function). MMRM was used to analyze the change from baseline for domagrozumab compared to placebo. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.

Outcome measures

Measure	Placebo n=40 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg n=80 Participants Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Change From Baseline as Compared to Placebo on the Northstar Ambulatory Assessment (NSAA) at Weeks 17, 33 and 49 Week 17	-1.9 Units on a scale Standard Error 0.8	-1.1 Units on a scale Standard Error 0.6	—	—
Change From Baseline as Compared to Placebo on the Northstar Ambulatory Assessment (NSAA) at Weeks 17, 33 and 49 Week 33	-4.5 Units on a scale Standard Error 0.8	-2.0 Units on a scale Standard Error 0.6	—	—
Change From Baseline as Compared to Placebo on the Northstar Ambulatory Assessment (NSAA) at Weeks 17, 33 and 49 Week 49	-5.2 Units on a scale Standard Error 0.9	-3.6 Units on a scale Standard Error 0.7	—	—

SECONDARY outcome

Timeframe: Baseline, Weeks 17, 33 and 49

Population: This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.

ROM was evaluated by using goniometry to evaluate the loss of motion in the ankles. MMRM was used to analyze the change from baseline on ROM for domagrozumab compared to placebo. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.

Outcome measures

Measure	Placebo n=40 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg n=80 Participants Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Change From Baseline as Compared to Placebo on the Ankle Range of Motion (ROM) at Weeks 17, 33 and 49 Right ankle, Week 49	-3.6 Degrees of passive dorsiflexion Standard Error 1.4	-3.6 Degrees of passive dorsiflexion Standard Error 1.1	—	—
Change From Baseline as Compared to Placebo on the Ankle Range of Motion (ROM) at Weeks 17, 33 and 49 Left ankle, Week 17	-1.0 Degrees of passive dorsiflexion Standard Error 1.2	-1.4 Degrees of passive dorsiflexion Standard Error 0.9	—	—
Change From Baseline as Compared to Placebo on the Ankle Range of Motion (ROM) at Weeks 17, 33 and 49 Left ankle, Week 33	-1.9 Degrees of passive dorsiflexion Standard Error 1.2	-1.7 Degrees of passive dorsiflexion Standard Error 0.9	—	—
Change From Baseline as Compared to Placebo on the Ankle Range of Motion (ROM) at Weeks 17, 33 and 49 Left ankle, Week 49	-2.3 Degrees of passive dorsiflexion Standard Error 1.3	-3.7 Degrees of passive dorsiflexion Standard Error 1.0	—	—
Change From Baseline as Compared to Placebo on the Ankle Range of Motion (ROM) at Weeks 17, 33 and 49 Right ankle, Week 17	-2.1 Degrees of passive dorsiflexion Standard Error 1.3	-1.3 Degrees of passive dorsiflexion Standard Error 1.0	—	—
Change From Baseline as Compared to Placebo on the Ankle Range of Motion (ROM) at Weeks 17, 33 and 49 Right ankle, Week 33	-4.1 Degrees of passive dorsiflexion Standard Error 1.3	-1.3 Degrees of passive dorsiflexion Standard Error 0.9	—	—

SECONDARY outcome

Timeframe: Baseline, Weeks 17, 33 and 49

Population: This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of timepoints.

The PUL was used to assess motor performance of the upper limb. The PUL scale includes 22 items; an entry item defining the starting functional level, and 21 items subdivided into three levels: shoulder (4 items), middle (9 items) and distal (8 items). Scoring options per item may not be uniform and may vary from 0-1 and 0-6, according to the performance, with higher values corresponding to better performance. A total maximum score of 74 is achieved by adding the individual level scores. MMRM was used to analyze the change from baseline for domagrozumab compared to placebo. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.

Outcome measures

Measure	Placebo n=40 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg n=80 Participants Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Change From Baseline as Compared to Placebo on the Performance of Upper Limb (PUL) Overall Score at Weeks 17, 33 and 49 Week 17	-0.7 Units on a scale Standard Error 0.6	-1.0 Units on a scale Standard Error 0.4	—	—
Change From Baseline as Compared to Placebo on the Performance of Upper Limb (PUL) Overall Score at Weeks 17, 33 and 49 Week 33	-2.7 Units on a scale Standard Error 1.1	-0.9 Units on a scale Standard Error 0.8	—	—
Change From Baseline as Compared to Placebo on the Performance of Upper Limb (PUL) Overall Score at Weeks 17, 33 and 49 Week 49	-1.3 Units on a scale Standard Error 0.5	-1.4 Units on a scale Standard Error 0.4	—	—

SECONDARY outcome

Timeframe: Baseline, Weeks 17, 33 and 49

Population: This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of timepoints.

6MWD evaluated ambulation ability by measuring the distance walked in 6 minutes. MMRM was used to analyze the change from baseline on 6MWD for domagrozumab compared to placebo. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.

Outcome measures

Measure	Placebo n=40 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg n=80 Participants Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Change From Baseline as Compared to Placebo on the Six Minute Walk Distance (6MWD) Score at Weeks 17, 33 and 49 Week 17	-32.0 Meters Standard Error 9.1	-30.2 Meters Standard Error 6.9	—	—
Change From Baseline as Compared to Placebo on the Six Minute Walk Distance (6MWD) Score at Weeks 17, 33 and 49 Week 33	-52.3 Meters Standard Error 9.9	-43.4 Meters Standard Error 7.4	—	—
Change From Baseline as Compared to Placebo on the Six Minute Walk Distance (6MWD) Score at Weeks 17, 33 and 49 Week 49	-56.5 Meters Standard Error 12.7	-58.0 Meters Standard Error 9.3	—	—

SECONDARY outcome

Timeframe: Baseline, Weeks 17, 33 and 49

Population: This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.

Muscle strength was quantified by means of a handheld dynamometer. The following muscle groups were evaluated: knee extension, elbow flexion, hip abduction, elbow extension and shoulder abduction. MMRM was used to analyze the change from baseline on muscle strength for domagrozumab compared to placebo. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.

Outcome measures

Measure	Placebo n=40 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg n=80 Participants Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Change From Baseline as Compared to Placebo on Muscle Strength of Elbow Extension at Weeks 17, 33 and 49 Left elbow extension, Week 17	-0.182 Kilograms Standard Error 0.183	-0.067 Kilograms Standard Error 0.141	—	—
Change From Baseline as Compared to Placebo on Muscle Strength of Elbow Extension at Weeks 17, 33 and 49 Left elbow extension, Week 33	-0.213 Kilograms Standard Error 0.187	-0.376 Kilograms Standard Error 0.141	—	—
Change From Baseline as Compared to Placebo on Muscle Strength of Elbow Extension at Weeks 17, 33 and 49 Left elbow extension, Week 49	-0.353 Kilograms Standard Error 0.200	-0.479 Kilograms Standard Error 0.150	—	—
Change From Baseline as Compared to Placebo on Muscle Strength of Elbow Extension at Weeks 17, 33 and 49 Right elbow extension, Week 17	-0.064 Kilograms Standard Error 0.209	-0.086 Kilograms Standard Error 0.158	—	—
Change From Baseline as Compared to Placebo on Muscle Strength of Elbow Extension at Weeks 17, 33 and 49 Right elbow extension, Week 33	-0.052 Kilograms Standard Error 0.197	-0.491 Kilograms Standard Error 0.148	—	—
Change From Baseline as Compared to Placebo on Muscle Strength of Elbow Extension at Weeks 17, 33 and 49 Right elbow extension, Week 49	-0.396 Kilograms Standard Error 0.192	-0.562 Kilograms Standard Error 0.145	—	—

SECONDARY outcome

Timeframe: Baseline, Weeks 17, 33 and 49

Population: This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.

Muscle strength was quantified by means of a handheld dynamometer. The following muscle groups were evaluated: knee extension, elbow flexion, hip abduction, elbow extension and shoulder abduction. MMRM was used to analyze the change from baseline on muscle strength for domagrozumab compared to placebo. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.

Outcome measures

Measure	Placebo n=40 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg n=80 Participants Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Change From Baseline as Compared to Placebo on Muscle Strength of Elbow Flexion at Weeks 17, 33 and 49 Left elbow flexion, Week 17	-0.096 Kilograms Standard Error 0.237	-0.252 Kilograms Standard Error 0.181	—	—
Change From Baseline as Compared to Placebo on Muscle Strength of Elbow Flexion at Weeks 17, 33 and 49 Left elbow flexion, Week 33	-0.194 Kilograms Standard Error 0.244	-0.497 Kilograms Standard Error 0.183	—	—
Change From Baseline as Compared to Placebo on Muscle Strength of Elbow Flexion at Weeks 17, 33 and 49 Left elbow flexion, Week 49	-0.573 Kilograms Standard Error 0.205	-0.734 Kilograms Standard Error 0.159	—	—
Change From Baseline as Compared to Placebo on Muscle Strength of Elbow Flexion at Weeks 17, 33 and 49 Right elbow flexion, Week 17	-0.035 Kilograms Standard Error 0.220	-0.118 Kilograms Standard Error 0.168	—	—
Change From Baseline as Compared to Placebo on Muscle Strength of Elbow Flexion at Weeks 17, 33 and 49 Right elbow flexion, Week 33	-0.057 Kilograms Standard Error 0.234	-0.418 Kilograms Standard Error 0.175	—	—
Change From Baseline as Compared to Placebo on Muscle Strength of Elbow Flexion at Weeks 17, 33 and 49 Right elbow flexion, Week 49	-0.495 Kilograms Standard Error 0.199	-0.684 Kilograms Standard Error 0.152	—	—

SECONDARY outcome

Timeframe: Baseline, Weeks 17, 33 and 49

Population: This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.

Muscle strength was quantified by means of a handheld dynamometer. The following muscle groups were evaluated: knee extension, elbow flexion, hip abduction, elbow extension and shoulder abduction. MMRM was used to analyze the change from baseline on muscle strength for domagrozumab compared to placebo. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.

Outcome measures

Measure	Placebo n=40 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg n=80 Participants Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Change From Baseline as Compared to Placebo on Muscle Strength of Hip Abduction at Weeks 17, 33 and 49 Left hip abduction, Week 17	0.430 Kilograms Standard Error 0.321	-0.156 Kilograms Standard Error 0.245	—	—
Change From Baseline as Compared to Placebo on Muscle Strength of Hip Abduction at Weeks 17, 33 and 49 Left hip abduction, Week 33	-0.217 Kilograms Standard Error 0.318	-0.171 Kilograms Standard Error 0.236	—	—
Change From Baseline as Compared to Placebo on Muscle Strength of Hip Abduction at Weeks 17, 33 and 49 Left hip abduction, Week 49	-0.097 Kilograms Standard Error 0.334	-0.475 Kilograms Standard Error 0.251	—	—
Change From Baseline as Compared to Placebo on Muscle Strength of Hip Abduction at Weeks 17, 33 and 49 Right hip abduction, Week 17	0.535 Kilograms Standard Error 0.320	-0.154 Kilograms Standard Error 0.247	—	—
Change From Baseline as Compared to Placebo on Muscle Strength of Hip Abduction at Weeks 17, 33 and 49 Right hip abduction, Week 33	0.087 Kilograms Standard Error 0.340	-0.249 Kilograms Standard Error 0.255	—	—
Change From Baseline as Compared to Placebo on Muscle Strength of Hip Abduction at Weeks 17, 33 and 49 Right hip abduction, Week 49	0.056 Kilograms Standard Error 0.343	-0.266 Kilograms Standard Error 0.260	—	—

SECONDARY outcome

Timeframe: Baseline, Weeks 17, 33 and 49

Population: This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.

Muscle strength was quantified by means of a handheld dynamometer. The following muscle groups were evaluated: knee extension, elbow flexion, hip abduction, elbow extension and shoulder abduction. MMRM was used to analyze the change from baseline on muscle strength for domagrozumab compared to placebo. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.

Outcome measures

Measure	Placebo n=40 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg n=80 Participants Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Change From Baseline as Compared to Placebo on Muscle Strength of Knee Extension at Weeks 17, 33 and 49 Left knee extension, Week 17	-0.326 Kilograms Standard Error 0.336	-0.434 Kilograms Standard Error 0.261	—	—
Change From Baseline as Compared to Placebo on Muscle Strength of Knee Extension at Weeks 17, 33 and 49 Left knee extension, Week 33	-0.713 Kilograms Standard Error 0.359	-1.036 Kilograms Standard Error 0.272	—	—
Change From Baseline as Compared to Placebo on Muscle Strength of Knee Extension at Weeks 17, 33 and 49 Left knee extension, Week 49	-1.223 Kilograms Standard Error 0.369	-1.110 Kilograms Standard Error 0.279	—	—
Change From Baseline as Compared to Placebo on Muscle Strength of Knee Extension at Weeks 17, 33 and 49 Right knee extension, Week 17	-0.213 Kilograms Standard Error 0.328	-0.450 Kilograms Standard Error 0.253	—	—
Change From Baseline as Compared to Placebo on Muscle Strength of Knee Extension at Weeks 17, 33 and 49 Right knee extension, Week 33	-0.413 Kilograms Standard Error 0.380	-0.880 Kilograms Standard Error 0.283	—	—
Change From Baseline as Compared to Placebo on Muscle Strength of Knee Extension at Weeks 17, 33 and 49 Right knee extension, Week 49	-0.976 Kilograms Standard Error 0.391	-1.125 Kilograms Standard Error 0.292	—	—

SECONDARY outcome

Timeframe: Baseline, Weeks 17, 33 and 49

Population: This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.

Muscle strength was quantified by means of a handheld dynamometer. The following muscle groups were evaluated: knee extension, elbow flexion, hip abduction, elbow extension and shoulder abduction. MMRM was used to analyze the change from baseline on muscle strength for domagrozumab compared to placebo. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.

Outcome measures

Measure	Placebo n=40 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg n=80 Participants Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Change From Baseline as Compared to Placebo on Muscle Strength of Shoulder Abduction at Weeks 17, 33 and 49 Right shoulder abduction, Week 33	0.421 Kilograms Standard Error 0.251	-0.336 Kilograms Standard Error 0.185	—	—
Change From Baseline as Compared to Placebo on Muscle Strength of Shoulder Abduction at Weeks 17, 33 and 49 Right shoulder abduction, Week 49	0.140 Kilograms Standard Error 0.313	-0.300 Kilograms Standard Error 0.229	—	—
Change From Baseline as Compared to Placebo on Muscle Strength of Shoulder Abduction at Weeks 17, 33 and 49 Left shoulder abduction, Week 17	-0.099 Kilograms Standard Error 0.213	-0.143 Kilograms Standard Error 0.163	—	—
Change From Baseline as Compared to Placebo on Muscle Strength of Shoulder Abduction at Weeks 17, 33 and 49 Left shoulder abduction, Week 33	-0.123 Kilograms Standard Error 0.226	-0.278 Kilograms Standard Error 0.166	—	—
Change From Baseline as Compared to Placebo on Muscle Strength of Shoulder Abduction at Weeks 17, 33 and 49 Left shoulder abduction, Week 49	-0.296 Kilograms Standard Error 0.238	-0.319 Kilograms Standard Error 0.177	—	—
Change From Baseline as Compared to Placebo on Muscle Strength of Shoulder Abduction at Weeks 17, 33 and 49 Right shoulder abduction, Week 17	0.079 Kilograms Standard Error 0.217	-0.157 Kilograms Standard Error 0.165	—	—

SECONDARY outcome

Timeframe: Baseline, Week 49

Population: This analysis population included all participants randomized in Sequence 3 and received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure.

The 4SC quantified the time required for a participant to ascend 4 standard steps. MMRM was used to analyze the change from baseline on 4SC for the natural history control group compared to placebo group (Sequence 3). This MMRM was established to assess the appropriateness on using the natural history control group as a comparator. The natural history control group was established by filtering the CINRG (Cooperative International Neuromuscular Research Group) natural history database. Participants who met the following requirements at baseline and had evaluable 4SC data on Week 49 were included in this group: 1) age: 6 to <16 years; 2)treatment of glucocorticoid steroids >=6 months prior to baseline and continuous use until the latest visit week; 3) 4SC: 2-15.9 seconds; 4) participants who were ambulatory at baseline; 5) LVEF: >=55% or missing.

Outcome measures

Measure	Placebo n=32 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Change From Baseline to Week 49 on 4SC for Participants in Sequence 3 Compared to the Natural History Control Group	3.464 Seconds Standard Error 1.232	—	—	—

SECONDARY outcome

Timeframe: Baseline, Week 97

Population: This analysis population included all participants randomized in Sequence 1 and received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure.

The 4SC quantified the time required for a participant to ascend 4 standard steps. MMRM was used to analyze the change from baseline on 4SC for domagrozumab compared to the natural history control group. The natural history control group was established by filtering the CINRG natural history database. Participants who met the following requirements at baseline and had evaluable 4SC data on Week 97 were included in this group: 1) age: 6 to <16 years; 2) treatment of glucocorticoid steroids >=6 months prior to baseline and continuous use until the latest visit week; 3) 4SC: 2-15.9 seconds; 4 participants who were ambulatory at baseline; 5) LVEF: >=55% or missing.

Outcome measures

Measure	Placebo n=18 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Change From Baseline to Week 97 on 4SC for Participants in Sequence 1 Compared to the Natural History Control Group	4.205 Seconds Standard Error 1.011	—	—	—

SECONDARY outcome

Timeframe: Baseline, Week 49

Population: This analysis population included all participants randomized in Sequence 3 and received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure.

FVC was measured by spirometry to evaluate respiratory muscle function. MMRM was used to analyze the change from baseline on FVC for the natural history control group compared to placebo group (Sequence 3). MMRM was used to analyze the change from baseline on FVC for the natural history control group compared to placebo group (Sequence 3). This MMRM was established to assess the appropriateness on using the natural history control group as a comparator. The natural history control group was established by filtering the CINRG natural history database. Participants who met the following requirements at baseline and had evaluable FVC data on Week 49 were included in this group: 1) age: 6 to <16 years; 2)treatment of glucocorticoid steroids >=6 months prior to baseline and continuous use until the latest visit week; 3) 4SC: 2-15.9 seconds; 4) participants who were ambulatory at baseline; 5) LVEF: >=55% or missing.

Outcome measures

Measure	Placebo n=38 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Change From Baseline to Week 49 on FVC for Participants in Sequence 3 Compared to the Natural History Control Group	0.1358 Liters Standard Error 0.0328	—	—	—

SECONDARY outcome

Timeframe: Baseline, Week 97

Population: This analysis population included all participants randomized in Sequence 1 and received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure.

FVC was measured by spirometry to evaluate respiratory muscle function. MMRM was used to analyze the change from baseline on FVC for domagrozumab compared to the natural history control group. The natural history control group was established by filtering the CINRG natural history database. Participants who met the following requirements at baseline and had evaluable FVC data on Week 97 were included in this group: 1) age: 6 to <16 years; 2) treatment of glucocorticoid steroids >=6 months prior to baseline and continuous use until the latest visit week; 3) 4SC: 2-15.9 seconds; 4 participants who were ambulatory at baseline; 5) LVEF: >=55% or missing.

Outcome measures

Measure	Placebo n=22 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Change From Baseline to Week 97 on FVC for Participants in Sequence 1 Compared to the Natural History Control Group	0.2528 Liters Standard Error 0.0508	—	—	—

SECONDARY outcome

Timeframe: Baseline, Week 49

Population: This analysis population included all participants randomized in Sequence 3 and received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure.

The NSAA is a 17-item test that measured gross motor function. A total score could range from 0 to 34 (fully-independent function). MMRM was used to analyze the change from baseline on NSAA for the natural history control group compared to placebo group (Sequence 3). This MMRM was established to assess the appropriateness on the using natural history control group as a comparator. The natural history control group was established by filtering the CINRG natural history database. Participants who met the following requirements at baseline and had evaluable NSAA data on Week 49 were included in this group: 1) age: 6 to <16 years; 2)treatment of glucocorticoid steroids >=6 months prior to baseline and continuous use until the latest visit week; 3) 4SC: 2-15.9 seconds; 4) participants who were ambulatory at baseline; 5) LVEF: >=55% or missing.

Outcome measures

Measure	Placebo n=37 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Change From Baseline to Week 49 on NSAA for Participants in Sequence 3 Compared to the Natural History Control Group	-4.8 Units on a scale Standard Error 1.2	—	—	—

SECONDARY outcome

Timeframe: Baseline, Week 97

Population: This analysis population included all participants randomized in Sequence 1 and received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure.

The NSAA is a 17-item test that measured gross motor function. The total score could range from 0 to 34 (fully-independent function). MMRM was used to analyze the change from baseline on NSAA for domagrozumab compared to the natural history control group. The natural history control group was established by filtering the CINRG natural history database. Participants who met the following requirements at baseline and had evaluable NSAA data on Week 97 were included in this group: 1) age: 6 to <16 years; 2) treatment of glucocorticoid steroids >=6 months prior to baseline and continuous use until the latest visit week; 3) 4SC: 2-15.9 seconds; 4 participants who were ambulatory at baseline; 5) LVEF: >=55% or missing.

Outcome measures

Measure	Placebo n=21 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Change From Baseline to Week 97 on NSAA for Participants in Sequence 1 Compared to the Natural History Control Group	-4.5 Units on a scale Standard Error 1.2	—	—	—

SECONDARY outcome

Timeframe: Baseline, Week 49

Population: This analysis population included all participants randomized in Sequence 3 and received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure.

6MWD evaluated ambulation ability by measuring the distance walked in 6 minutes. MMRM was used to analyze the change from baseline on 6MWD for the natural history control group compared to placebo group (Sequence 3). This MMRM was established to assess the appropriateness on using the natural history control group as a comparator. The natural history control group was established by filtering the CINRG natural history database. Participants who met the following requirements at baseline and had evaluable 6MWD data on Week 49 were included in this group: 1) age: 6 to <16 years; 2)treatment of glucocorticoid steroids >=6 months prior to baseline and continuous use until the latest visit week; 3) 4SC: 2-15.9 seconds; 4) participants who were ambulatory at baseline; 5) LVEF: >=55% or missing.

Outcome measures

Measure	Placebo n=30 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Change From Baseline to Week 49 on 6MWD for Participants in Sequence 3 Compared to the Natural History Control Group	-80.8 Meters Standard Error 19.3	—	—	—

SECONDARY outcome

Timeframe: Baseline, Week 97

Population: This analysis population included all participants randomized in Sequence 1 and received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure.

6MWD evaluated ambulation ability by measuring the distance walked in 6 minutes. MMRM was used to analyze the change from baseline on 6MWD for domagrozumab compared to the natural history control group. The natural history control group was established by filtering the CINRG natural history database. Participants who met the following requirements at baseline and had evaluable 6MWD data on Week 97 were included in this group: 1) age: 6 to <16 years; 2)treatment of glucocorticoid steroids >=6 months prior to baseline and continuous use until the latest visit week; 3) 4SC: 2-15.9 seconds; 4) participants who were ambulatory at baseline; 5) LVEF: >=55% or missing.

Outcome measures

Measure	Placebo n=17 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Change From Baseline to Week 97 on 6MWD for Participants in Sequence 1 Compared to the Natural History Control Group	-97.6 Meters Standard Error 20.7	—	—	—

SECONDARY outcome

Timeframe: Baseline, Week 17

Population: This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.

The 4SC quantified the time required for a participant to ascend 4 standard steps. A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time: 1) <3.5 seconds, 2)>=3.5 seconds and <=8 seconds, 3) >8 seconds. MMRM was used to analyze the change from baseline for domagrozumab compared to placebo in subsets. The baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.

Outcome measures

Measure	Placebo n=39 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg n=74 Participants Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Change From Baseline as Compared to Placebo on 4SC at Week 17 in Pre-specified Subsets Baseline 4SC<3.5 seconds	0.2329 Seconds Standard Error 0.1513	0.1637 Seconds Standard Error 0.092	—	—
Change From Baseline as Compared to Placebo on 4SC at Week 17 in Pre-specified Subsets Baseline 4SC>=3.5 and <=8 seconds	0.7644 Seconds Standard Error 0.4108	0.9758 Seconds Standard Error 0.3283	—	—
Change From Baseline as Compared to Placebo on 4SC at Week 17 in Pre-specified Subsets Baseline 4SC>8 seconds	7.7149 Seconds Standard Error 4.8455	5.071 Seconds Standard Error 3.0969	—	—

SECONDARY outcome

Timeframe: Baseline, Week 33

Population: This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.

The 4SC quantified the time required for a participant to ascend 4 standard steps. A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time: 1) <3.5 seconds, 2)>=3.5 seconds and <=8 seconds, 3) >8 seconds.MMRM was used to analyze the change from baseline for domagrozumab compared to placebo in subsets. The baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.

Outcome measures

Measure	Placebo n=33 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg n=70 Participants Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Change From Baseline as Compared to Placebo on 4SC at Week 33 in Pre-specified Subsets Baseline 4SC<3.5 seconds	0.435 Seconds Standard Error 0.1852	0.1062 Seconds Standard Error 0.1061	—	—
Change From Baseline as Compared to Placebo on 4SC at Week 33 in Pre-specified Subsets Baseline 4SC>=3.5 and <=8 seconds	2.2085 Seconds Standard Error 0.8933	2.5542 Seconds Standard Error 0.7234	—	—
Change From Baseline as Compared to Placebo on 4SC at Week 33 in Pre-specified Subsets Baseline 4SC>8 seconds	3.7436 Seconds Standard Error 8.1156	12.0329 Seconds Standard Error 3.6174	—	—

SECONDARY outcome

Timeframe: Baseline, Week 49

Population: This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.

The 4SC quantified the time required for a participant to ascend 4 standard steps. A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time: 1) <3.5 seconds, 2)>=3.5 seconds and <=8 seconds, 3) >8 seconds. MMRM was used to analyze the change from baseline for domagrozumab compared to placebo in subsets. The baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.

Outcome measures

Measure	Placebo n=32 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg n=63 Participants Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Change From Baseline as Compared to Placebo on 4SC at Week 49 in Pre-specified Subsets Baseline 4SC<3.5 seconds	1.0056 Seconds Standard Error 0.294	0.4474 Seconds Standard Error 0.1816	—	—
Change From Baseline as Compared to Placebo on 4SC at Week 49 in Pre-specified Subsets Baseline 4SC>=3.5 and <= 8 seconds	3.526 Seconds Standard Error 1.1574	3.6204 Seconds Standard Error 0.9391	—	—
Change From Baseline as Compared to Placebo on 4SC at Week 49 in Pre-specified Subsets Baseline 4SC>8 seconds	30.3411 Seconds Standard Error 9.7373	19.053 Seconds Standard Error 4.1965	—	—

SECONDARY outcome

Timeframe: Baseline, Week 17

Population: This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.

FVC was measured by spirometry to evaluate respiratory muscle function. A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time: 1) <3.5 seconds, 2)>=3.5 seconds and <=8 seconds, 3) >8 seconds. MMRM was used to analyze the change from baseline on FVC for domagrozumab compared to placebo in subsets. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.

Outcome measures

Measure	Placebo n=40 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg n=78 Participants Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Change From Baseline as Compared to Placebo on FVC at Week 17 in Pre-specified Subsets Baseline 4SC<3.5 seconds	0.0562 Liters Standard Error 0.0603	0.0722 Liters Standard Error 0.0368	—	—
Change From Baseline as Compared to Placebo on FVC at Week 17 in Pre-specified Subsets Baseline 4SC>=3.5 and <=8 seconds	0.0543 Liters Standard Error 0.0352	0.0411 Liters Standard Error 0.0276	—	—
Change From Baseline as Compared to Placebo on FVC at Week 17 in Pre-specified Subsets Baseline 4SC>8 seconds	-0.0168 Liters Standard Error 0.0800	0.0721 Liters Standard Error 0.0534	—	—

SECONDARY outcome

Timeframe: Baseline, Week 33

Population: This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.

FVC was measured by spirometry to evaluate respiratory muscle function. A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time: 1) <3.5 seconds, 2)>=3.5 seconds and <=8 seconds, 3) >8 seconds. MMRM was used to analyze the change from baseline on FVC for domagrozumab compared to placebo in subsets. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.

Outcome measures

Measure	Placebo n=37 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg n=76 Participants Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Change From Baseline as Compared to Placebo on FVC at Week 33 in Pre-specified Subsets Baseline 4SC<3.5 seconds	0.1971 Liters Standard Error 0.0659	0.1036 Liters Standard Error 0.0389	—	—
Change From Baseline as Compared to Placebo on FVC at Week 33 in Pre-specified Subsets Baseline 4SC>=3.5 and <=8 seconds	0.0585 Liters Standard Error 0.0476	0.0468 Liters Standard Error 0.0376	—	—
Change From Baseline as Compared to Placebo on FVC at Week 33 in Pre-specified Subsets Baseline 4SC>8 seconds	0.0332 Liters Standard Error 0.1053	0.0895 Liters Standard Error 0.0703	—	—

SECONDARY outcome

Timeframe: Baseline, Week 49

Population: This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.

FVC was measured by spirometry to evaluate respiratory muscle function. A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time: 1) <3.5 seconds, 2)>=3.5 seconds and <=8 seconds, 3) >8 seconds. MMRM was used to analyze the change from baseline on FVC for domagrozumab compared to placebo in subsets. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.

Outcome measures

Measure	Placebo n=38 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg n=74 Participants Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Change From Baseline as Compared to Placebo on FVC at Week 49 in Pre-specified Subsets Baseline 4SC>8 seconds	0.0052 Liters Standard Error 0.0936	0.1091 Liters Standard Error 0.0634	—	—
Change From Baseline as Compared to Placebo on FVC at Week 49 in Pre-specified Subsets Baseline 4SC<3.5 seconds	0.2199 Liters Standard Error 0.0675	0.1186 Liters Standard Error 0.0418	—	—
Change From Baseline as Compared to Placebo on FVC at Week 49 in Pre-specified Subsets Baseline 4SC>=3.5 and <=8 seconds	0.1364 Liters Standard Error 0.0376	0.1006 Liters Standard Error 0.0297	—	—

SECONDARY outcome

Timeframe: Baseline, Week 17

Population: This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.

The NSAA is a 17-item test that measured gross motor function. Each individual item received a score of 0-unable to perform independently, 1-able to perform with assistance, or 2-able to perform without assistance. A total score was achieved by summing all the individual items. The total score could range from 0 to 34 (fully-independent function). A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time: 1) <3.5 seconds, 2)>=3.5 seconds and <=8 seconds, 3) >8 seconds. MMRM was used to analyze the change from baseline for domagrozumab compared to placebo in subsets. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.

Outcome measures

Measure	Placebo n=38 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg n=77 Participants Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Change From Baseline as Compared to Placebo on NSAA at Week 17 in Pre-specified Subsets Baseline 4SC<3.5 seconds	-0.4 Units on a scale Standard Error 1.8	-0.7 Units on a scale Standard Error 1.1	—	—
Change From Baseline as Compared to Placebo on NSAA at Week 17 in Pre-specified Subsets Baseline 4SC>=3.5 and <=8 seconds	-1.3 Units on a scale Standard Error 0.8	-0.1 Units on a scale Standard Error 0.6	—	—
Change From Baseline as Compared to Placebo on NSAA at Week 17 in Pre-specified Subsets Baseline 4SC>8 seconds	-3.2 Units on a scale Standard Error 0.9	-1.9 Units on a scale Standard Error 0.6	—	—

SECONDARY outcome

Timeframe: Baseline, Week 33

Population: This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.

The NSAA is a 17-item test that measured gross motor function. Each individual item received a score of 0-unable to perform independently, 1-able to perform with assistance, or 2-able to perform without assistance. A total score was achieved by summing all the individual items. The total score could range from 0 to 34 (fully-independent function). A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time: 1) <3.5 seconds, 2)>=3.5 seconds and <=8 seconds, 3) >8 seconds. MMRM was used to analyze the change from baseline for domagrozumab compared to placebo in subsets. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.

Outcome measures

Measure	Placebo n=38 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg n=75 Participants Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Change From Baseline as Compared to Placebo on NSAA at Week 33 in Pre-specified Subsets Baseline 4SC<3.5 seconds	-3.9 Units on a scale Standard Error 1.5	-0.4 Units on a scale Standard Error 0.9	—	—
Change From Baseline as Compared to Placebo on NSAA at Week 33 in Pre-specified Subsets Baseline 4SC>=3.5 and <=8 seconds	-3.5 Units on a scale Standard Error 1.0	-2.0 Units on a scale Standard Error 0.8	—	—
Change From Baseline as Compared to Placebo on NSAA at Week 33 in Pre-specified Subsets Baseline 4SC>8 seconds	-5.6 Units on a scale Standard Error 1.3	-2.7 Units on a scale Standard Error 0.9	—	—

SECONDARY outcome

Timeframe: Baseline, Week 49

Population: This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.

The NSAA is a 17-item test that measured gross motor function. Each individual item received a score of 0-unable to perform independently, 1-able to perform with assistance, or 2-able to perform without assistance. A total score was achieved by summing all the individual items. The total score could range from 0 to 34 (fully-independent function). A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time: 1) <3.5 seconds, 2)>=3.5 seconds and <=8 seconds, 3) >8 seconds. MMRM was used to analyze the change from baseline for domagrozumab compared to placebo in subsets. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.

Outcome measures

Measure	Placebo n=37 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg n=73 Participants Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Change From Baseline as Compared to Placebo on NSAA at Week 49 in Pre-specified Subsets Baseline 4SC<3.5 seconds	-3.8 Units on a scale Standard Error 1.8	-1.8 Units on a scale Standard Error 1.1	—	—
Change From Baseline as Compared to Placebo on NSAA at Week 49 in Pre-specified Subsets Baseline 4SC>=3.5 and <= 8 seconds	-4.2 Units on a scale Standard Error 1.1	-3.7 Units on a scale Standard Error 0.9	—	—
Change From Baseline as Compared to Placebo on NSAA at Week 49 in Pre-specified Subsets Baseline 4SC>8 seconds	-8.4 Units on a scale Standard Error 1.4	-4.4 Units on a scale Standard Error 0.9	—	—

SECONDARY outcome

Timeframe: Baseline, Week 17

Population: This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.

The PUL was used to assess motor performance of the upper limb. The PUL scale includes 22 items; an entry item defining the starting functional level, and 21 items subdivided into three levels: shoulder (4 items), middle (9 items) and distal (8 items). Scoring options per item may not be uniform and may vary from 0-1 and 0-6, according to the performance, with higher values corresponding to better performance. A total maximum score of 74 is achieved by adding the individual level scores. A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time. MMRM was used to analyze the change from baseline .The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.

Outcome measures

Measure	Placebo n=40 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg n=78 Participants Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Change From Baseline as Compared to Placebo on PUL Overall Scores at Week 17 in Pre-specified Subsets Baseline 4SC<3.5 seconds	-1.1 Units on a scale Standard Error 1.1	0.2 Units on a scale Standard Error 0.7	—	—
Change From Baseline as Compared to Placebo on PUL Overall Scores at Week 17 in Pre-specified Subsets Baseline 4SC>=3.5 and <=8 seconds	0.2 Units on a scale Standard Error 0.7	-1.0 Units on a scale Standard Error 0.5	—	—
Change From Baseline as Compared to Placebo on PUL Overall Scores at Week 17 in Pre-specified Subsets Baseline 4SC>8 seconds	0.4 Units on a scale Standard Error 1.7	-0.5 Units on a scale Standard Error 1.2	—	—

SECONDARY outcome

Timeframe: Baseline, Week 33

Population: This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.

The PUL was used to assess motor performance of the upper limb. The PUL scale includes 22 items; an entry item defining the starting functional level, and 21 items subdivided into three levels: shoulder (4 items), middle (9 items) and distal (8 items).Scoring options per item may not be uniform and may vary from 0-1 and 0-6, according to the performance, with higher values corresponding to better performance. A total maximum score of 74 is achieved by adding the individual level scores. A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time. MMRM was used to analyze the change from baseline.The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.

Outcome measures

Measure	Placebo n=37 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg n=76 Participants Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Change From Baseline as Compared to Placebo on PUL Overall Score at Week 33 in Pre-specified Subsets Baseline 4SC>8 seconds	-1.0 Units on a scale Standard Error 1.9	-2.0 Units on a scale Standard Error 1.2	—	—
Change From Baseline as Compared to Placebo on PUL Overall Score at Week 33 in Pre-specified Subsets Baseline 4SC<3.5 seconds	-6.4 Units on a scale Standard Error 3.3	0.1 Units on a scale Standard Error 2.0	—	—
Change From Baseline as Compared to Placebo on PUL Overall Score at Week 33 in Pre-specified Subsets Baseline 4SC>=3.5 and <= 8 seconds	0 Units on a scale Standard Error 0.6	-0.3 Units on a scale Standard Error 0.5	—	—

SECONDARY outcome

Timeframe: Baseline, Week 49

Population: This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.

The PUL was used to assess motor performance of the upper limb. The PUL scale includes 22 items; an entry item defining the starting functional level, and 21 items subdivided into three levels: shoulder (4 items), middle (9 items) and distal (8 items).Scoring options per item may not be uniform and may vary from 0-1 and 0-6, according to the performance, with higher values corresponding to better performance. A total maximum score of 74 is achieved by adding the individual level scores. A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time. MMRM was used to analyze the change from baseline.The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.

Outcome measures

Measure	Placebo n=38 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg n=75 Participants Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Change From Baseline as Compared to Placebo on PUL Overall Score at Week 49 in Pre-specified Subsets Baseline 4SC<3.5 seconds	0.3 Units on a scale Standard Error 0.6	0.3 Units on a scale Standard Error 0.4	—	—
Change From Baseline as Compared to Placebo on PUL Overall Score at Week 49 in Pre-specified Subsets Baseline 4SC>=3.5 and <=8 seconds	-0.9 Units on a scale Standard Error 0.7	-1.0 Units on a scale Standard Error 0.5	—	—
Change From Baseline as Compared to Placebo on PUL Overall Score at Week 49 in Pre-specified Subsets Baseline 4SC>8 seconds	-2.6 Units on a scale Standard Error 1.7	-3.5 Units on a scale Standard Error 1.1	—	—

SECONDARY outcome

Timeframe: Baseline, Week 17

Population: This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.

6MWD evaluated ambulation ability by measuring the distance walked in 6 minutes. A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time: 1) <3.5 seconds, 2)>=3.5 seconds and <=8 seconds, 3) >8 seconds. MMRM was used to analyze the change from baseline on 6MWD for domagrozumab compared to placebo in subsets. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.

Outcome measures

Measure	Placebo n=36 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg n=74 Participants Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Change From Baseline as Compared to Placebo on 6MWD at Week 17 in Pre-specified Subsets Baseline 4SC<3.5 seconds	-6.9 Meters Standard Error 15.4	-12.7 Meters Standard Error 9.3	—	—
Change From Baseline as Compared to Placebo on 6MWD at Week 17 in Pre-specified Subsets Baseline 4SC>=3.5 and <=8 seconds	-21.0 Meters Standard Error 8.8	-22.4 Meters Standard Error 7.0	—	—
Change From Baseline as Compared to Placebo on 6MWD at Week 17 in Pre-specified Subsets Baseline 4SC>8 seconds	-34.0 Meters Standard Error 28.3	-20.9 Meters Standard Error 16.3	—	—

SECONDARY outcome

Timeframe: Baseline, Week 33

Population: This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.

6MWD evaluated ambulation ability by measuring the distance walked in 6 minutes. A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time: 1) <3.5 seconds, 2)>=3.5 seconds and <=8 seconds, 3) >8 seconds. MMRM was used to analyze the change from baseline on 6MWD for domagrozumab compared to placebo in subsets. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.

Outcome measures

Measure	Placebo n=31 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg n=70 Participants Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Change From Baseline as Compared to Placebo on 6MWD at Week 33 in Pre-specified Subsets Baseline 4SC<3.5 seconds	-12.0 Meters Standard Error 13.2	-15.7 Meters Standard Error 7.8	—	—
Change From Baseline as Compared to Placebo on 6MWD at Week 33 in Pre-specified Subsets Baseline 4SC>=3.5 and <=8 seconds	-45.7 Meters Standard Error 10.9	-38.4 Meters Standard Error 8.6	—	—
Change From Baseline as Compared to Placebo on 6MWD at Week 33 in Pre-specified Subsets Baseline 4SC>8 seconds	-71.9 Meters Standard Error 40.6	-55.6 Meters Standard Error 17.5	—	—

SECONDARY outcome

Timeframe: Baseline, Week 49

Population: This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.

6MWD evaluated ambulation ability by measuring the distance walked in 6 minutes. A subset analysis was performed by categorizing participants into 3 subsets according to the baseline 4SC time: 1) <3.5 seconds, 2)>=3.5 seconds and <=8 seconds, 3) >8 seconds. MMRM was used to analyze the change from baseline on 6MWD for domagrozumab compared to placebo in subsets. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.

Outcome measures

Measure	Placebo n=30 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg n=61 Participants Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Change From Baseline as Compared to Placebo on 6MWD at Week 49 in Pre-specified Subsets Baseline 4SC<3.5 seconds	-33.5 Meters Standard Error 16.4	-26.5 Meters Standard Error 10.1	—	—
Change From Baseline as Compared to Placebo on 6MWD at Week 49 in Pre-specified Subsets Baseline 4SC>=3.5 and <=8 seconds	-42.0 Meters Standard Error 16.7	-57.8 Meters Standard Error 13.4	—	—
Change From Baseline as Compared to Placebo on 6MWD at Week 49 in Pre-specified Subsets Baseline 4SC>8 seconds	-75.1 Meters Standard Error 47.6	-71.2 Meters Standard Error 18.9	—	—

SECONDARY outcome

Timeframe: Baseline, Weeks 17, 33 and 49

Population: This analysis population included all participants (with baseline 4SC \<3.5 seconds) randomized and who had received at least 1 dose o f randomized treatment. Number analyzed refers to number of participants evaluable for specified rows of categories.

Muscle strength was quantified by means of a handheld dynamometer. The following muscle groups were evaluated: knee extension, elbow flexion, hip abduction, elbow extension and shoulder abduction. Change from baseline on muscle strength in all participants with baseline 4SC <3.5 seconds are presented below.

Outcome measures

Measure	Placebo n=11 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg n=30 Participants Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) Right knee extension, Week 17	1.01 Kilograms Interval -0.395 to 2.413	-0.97 Kilograms Interval -2.035 to 0.092	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) Right shoulder abduction, Week 49	0.17 Kilograms Interval -0.749 to 1.089	-0.20 Kilograms Interval -0.852 to 0.445	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) Left elbow extension, Week 17	-0.08 Kilograms Interval -0.811 to 0.647	-0.33 Kilograms Interval -0.96 to 0.301	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) Left elbow extension, Week 33	-0.30 Kilograms Interval -1.217 to 0.617	-0.61 Kilograms Interval -1.263 to 0.042	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) Left elbow extension, Week 49	-1.13 Kilograms Interval -2.13 to -0.13	-0.60 Kilograms Interval -1.304 to 0.097	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) Right elbow extension, Week 17	0.35 Kilograms Interval -0.26 to 0.969	-0.50 Kilograms Interval -1.305 to 0.297	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) Right elbow extension, Week 33	0.46 Kilograms Interval -0.681 to 1.606	-0.88 Kilograms Interval -1.591 to -0.168	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) Right elbow extension, Week 49	-0.74 Kilograms Interval -1.727 to 0.247	-0.78 Kilograms Interval -1.601 to 0.037	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) Left elbow flexion, Week 17	0.65 Kilograms Interval -0.29 to 1.6	-0.61 Kilograms Interval -1.602 to 0.387	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) Left elbow flexion, Week 33	0.95 Kilograms Interval -0.7 to 2.6	-0.77 Kilograms Interval -1.628 to 0.083	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) Left elbow flexion, Week 49	-0.88 Kilograms Interval -1.664 to -0.096	-0.96 Kilograms Interval -1.857 to -0.057	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) Right elbow flexion, Week 17	1.29 Kilograms Interval 0.401 to 2.181	-0.21 Kilograms Interval -0.938 to 0.517	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) Right elbow flexion, Week 33	1.38 Kilograms Interval -0.806 to 3.556	-0.35 Kilograms Interval -0.913 to 0.217	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) Right elbow flexion, Week 49	-0.33 Kilograms Interval -1.082 to 0.422	-0.69 Kilograms Interval -1.31 to -0.061	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) Left hip abduction, Week 17	0.62 Kilograms Interval -0.774 to 2.011	-0.18 Kilograms Interval -1.206 to 0.849	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) Left hip abduction, Week 33	-0.51 Kilograms Interval -2.235 to 1.21	-0.02 Kilograms Interval -0.835 to 0.786	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) Left hip abduction, Week 49	-1.18 Kilograms Interval -2.358 to -0.002	-0.30 Kilograms Interval -1.001 to 0.394	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) Right hip abduction, Week 17	1.47 Kilograms Interval 0.185 to 2.76	-0.26 Kilograms Interval -1.295 to 0.781	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) Right hip abduction, Week 33	0.40 Kilograms Interval -0.739 to 1.539	-0.34 Kilograms Interval -1.172 to 0.496	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) Right hip abduction, Week 49	-0.75 Kilograms Interval -1.785 to 0.285	-0.14 Kilograms Interval -1.121 to 0.831	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) Left knee extension, Week 17	0.99 Kilograms Interval -0.192 to 2.174	-1.12 Kilograms Interval -2.186 to -0.05	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) Left knee extension, Week 33	0.11 Kilograms Interval -2.096 to 2.321	-1.31 Kilograms Interval -2.367 to -0.261	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) Left knee extension, Week 49	-1.54 Kilograms Interval -3.308 to 0.228	-1.33 Kilograms Interval -2.516 to -0.14	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) Right knee extension, Week 33	0.26 Kilograms Interval -1.037 to 1.562	-1.31 Kilograms Interval -2.494 to -0.12	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) Right knee extension, Week 49	-1.79 Kilograms Interval -4.347 to 0.767	-1.47 Kilograms Interval -2.646 to -0.299	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) Left shoulder abduction, Week 17	0.66 Kilograms Interval -0.218 to 1.545	-0.33 Kilograms Interval -0.866 to 0.206	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) Left shoulder abduction, Week 33	0.48 Kilograms Interval -0.574 to 1.524	-0.32 Kilograms Interval -0.747 to 0.112	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) Left shoulder abduction, Week 49	-0.32 Kilograms Interval -1.357 to 0.717	-0.16 Kilograms Interval -0.627 to 0.306	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) Right shoulder abduction, Week 17	1.16 Kilograms Interval 0.421 to 1.899	-0.40 Kilograms Interval -1.058 to 0.258	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC <3.5 Seconds) Right shoulder abduction, Week 33	1.06 Kilograms Interval -0.222 to 2.347	-0.50 Kilograms Interval -1.02 to 0.027	—	—

SECONDARY outcome

Timeframe: Baseline, Weeks 17, 33 and 49

Population: This analysis population included all participants (with baseline 4SC \>=3.5 seconds and \<=8 seconds ) randomized and who had received at least 1 dose of randomized treatment. Number analyzed refers to number of participants evaluable for specified rows of categories.

Muscle strength was quantified by means of a handheld dynamometer. The following muscle groups were evaluated: knee extension, elbow flexion, hip abduction, elbow extension and shoulder abduction. Change from baseline on muscle strength in all participants with baseline 4SC >=3.5 seconds and <=8 seconds are presented below.

Outcome measures

Measure	Placebo n=24 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg n=38 Participants Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) Left elbow flexion, Week 17	-0.10 Kilograms Interval -0.523 to 0.331	0.31 Kilograms Interval -0.052 to 0.668	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) Left hip abduction, Week 49	0.48 Kilograms Interval -0.336 to 1.29	-0.09 Kilograms Interval -1.042 to 0.865	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) Left elbow extension, Week 17	-0.05 Kilograms Interval -0.353 to 0.244	0.31 Kilograms Interval -0.073 to 0.689	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) Left elbow extension, Week 33	-0.02 Kilograms Interval -0.441 to 0.396	-0.09 Kilograms Interval -0.48 to 0.302	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) Left elbow extension, Week 49	0.15 Kilograms Interval -0.223 to 0.532	-0.26 Kilograms Interval -0.803 to 0.289	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) Right elbow extension, Week 17	0 Kilograms Interval -0.297 to 0.297	0.31 Kilograms Interval -0.07 to 0.686	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) Right elbow extension, Week 33	0.02 Kilograms Interval -0.367 to 0.412	-0.17 Kilograms Interval -0.558 to 0.209	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) Right elbow extension, Week 49	-0.02 Kilograms Interval -0.294 to 0.257	-0.29 Kilograms Interval -0.735 to 0.146	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) Left elbow flexion, Week 33	-0.26 Kilograms Interval -0.598 to 0.071	-0.13 Kilograms Interval -0.515 to 0.254	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) Left elbow flexion, Week 49	-0.22 Kilograms Interval -0.719 to 0.273	-0.31 Kilograms Interval -0.766 to 0.149	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) Right elbow flexion,Week 17	-0.20 Kilograms Interval -0.471 to 0.063	0.19 Kilograms Interval -0.2 to 0.589	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) Right elbow flexion,Week 33	-0.15 Kilograms Interval -0.529 to 0.239	-0.23 Kilograms Interval -0.682 to 0.225	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) Right elbow flexion,Week 49	-0.21 Kilograms Interval -0.6 to 0.182	-0.43 Kilograms Interval -0.92 to 0.068	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) Left hip abduction, Week 17	0.65 Kilograms Interval -0.019 to 1.319	0.34 Kilograms Interval -0.134 to 0.823	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) Left hip abduction, Week 33	-0.04 Kilograms Interval -0.823 to 0.75	-0.02 Kilograms Interval -0.562 to 0.518	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) Right hip abduction, Week 17	0.30 Kilograms Interval -0.444 to 1.052	0.29 Kilograms Interval -0.189 to 0.779	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) Right hip abduction, Week 33	0 Kilograms Interval -1.062 to 1.071	-0.05 Kilograms Interval -0.655 to 0.555	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) Right hip abduction, Week 49	0.32 Kilograms Interval -0.555 to 1.2	0.20 Kilograms Interval -0.681 to 1.087	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) Left knee extension, Week 17	-0.51 Kilograms Interval -1.266 to 0.249	0.50 Kilograms Interval -0.025 to 1.025	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) Left knee extension, Week 33	-0.59 Kilograms Interval -1.576 to 0.404	-0.67 Kilograms Interval -1.339 to 0.0	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) Left knee extension, Week 49	-0.80 Kilograms Interval -1.856 to 0.256	-0.59 Kilograms Interval -1.373 to 0.201	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) Right knee extension, Week 17	-0.41 Kilograms Interval -1.092 to 0.267	0.14 Kilograms Interval -0.36 to 0.633	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) Right knee extension, Week 33	-0.35 Kilograms Interval -1.227 to 0.536	-0.53 Kilograms Interval -1.237 to 0.17	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) Right knee extension, Week 49	-0.33 Kilograms Interval -1.144 to 0.489	-0.69 Kilograms Interval -1.547 to 0.158	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) Left shoulder abduction, Week 17	-0.24 Kilograms Interval -0.757 to 0.274	0.49 Kilograms Interval 0.072 to 0.902	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) Left shoulder abduction, Week 33	-0.19 Kilograms Interval -0.552 to 0.17	0.03 Kilograms Interval -0.442 to 0.503	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) Left shoulder abduction, Week 49	-0.20 Kilograms Interval -0.679 to 0.288	-0.01 Kilograms Interval -0.749 to 0.727	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) Rightshoulder abduction, Week 17	-0.18 Kilograms Interval -0.493 to 0.134	0.14 Kilograms Interval -0.296 to 0.581	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) Right shoulder abduction, Week 33	0.38 Kilograms Interval -0.26 to 1.014	-0.18 Kilograms Interval -0.683 to 0.319	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >=3.5 Seconds and <=8 Seconds) Right shoulder abduction, Week 49	0.31 Kilograms Interval -0.167 to 0.785	-0.19 Kilograms Interval -1.168 to 0.78	—	—

SECONDARY outcome

Timeframe: Baseline, Weeks 17, 33 and 49

Population: This analysis population included all participants (with baseline 4SC \>8 seconds) randomized and who had received at least 1 dose of randomized treatment. Number analyzed refers to number of participants evaluable for specified rows of categories.

Muscle strength was quantified by means of a handheld dynamometer. The following muscle groups were evaluated: knee extension, elbow flexion, hip abduction, elbow extension and shoulder abduction. Change from baseline on muscle strength in all participants with baseline 4SC >8 seconds are presented below.

Outcome measures

Measure	Placebo n=5 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg n=12 Participants Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) Right elbow extension, Week 17	0.32 Kilograms Interval -0.231 to 0.871	0.41 Kilograms Interval 0.099 to 0.719	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) Left elbow extension, Week 17	0.10 Kilograms Interval -0.665 to 0.865	0.14 Kilograms Interval -0.226 to 0.498	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) Left elbow extension, Week 33	0.14 Kilograms Interval -0.672 to 0.952	0.06 Kilograms Interval -0.485 to 0.612	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) Left elbow extension, Week 49	0.08 Kilograms Interval -0.38 to 0.54	-0.15 Kilograms Interval -0.456 to 0.146	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) Right elbow extension, Week 33	0.10 Kilograms Interval -0.434 to 0.634	0.23 Kilograms Interval -0.38 to 0.834	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) Right elbow extension, Week 49	0.06 Kilograms Interval -0.275 to 0.395	-0.13 Kilograms Interval -0.467 to 0.213	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) Left elbow flexion, Week 17	-0.12 Kilograms Interval -0.657 to 0.417	0.10 Kilograms Interval -0.199 to 0.399	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) Left elbow flexion, Week 33	-0.36 Kilograms Interval -1.108 to 0.388	0.33 Kilograms Interval -0.684 to 1.339	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) Left elbow flexion, Week 49	-0.34 Kilograms Interval -0.81 to 0.13	-0.27 Kilograms Interval -0.691 to 0.146	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) Right elbow flexion, Week 17	-0.30 Kilograms Interval -0.933 to 0.333	0.20 Kilograms Interval -0.168 to 0.568	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) Right elbow flexion, Week 33	-0.02 Kilograms Interval -0.488 to 0.448	0.12 Kilograms Interval -0.671 to 0.908	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) Right elbow flexion, Week 49	-0.14 Kilograms Interval -0.567 to 0.287	-0.34 Kilograms Interval -0.646 to -0.027	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) Left hip abduction, Week 17	0.12 Kilograms Interval -1.321 to 1.561	-0.18 Kilograms Interval -1.104 to 0.741	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) Left hip abduction, Week 33	0.36 Kilograms Interval -1.232 to 1.952	0.65 Kilograms Interval -1.112 to 2.403	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) Left hip abduction, Week 49	0.16 Kilograms Interval -1.785 to 2.105	-0.68 Kilograms Interval -1.714 to 0.351	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) Right hip abduction, Week 17	0.22 Kilograms Interval -0.698 to 1.138	0.09 Kilograms Interval -0.546 to 0.728	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) Right hip abduction, Week 33	0.32 Kilograms Interval -1.826 to 2.466	0.80 Kilograms Interval -1.501 to 3.101	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) Right hip abduction, Week 49	0.68 Kilograms Interval -1.743 to 3.103	-0.55 Kilograms Interval -1.569 to 0.46	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) Left knee extension, Week 17	0.04 Kilograms Interval -0.505 to 0.585	0.22 Kilograms Interval -0.052 to 0.488	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) Left knee extension, Week 33	-0.24 Kilograms Interval -1.188 to 0.708	0.32 Kilograms Interval -0.749 to 1.386	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) Left knee extension, Week 49	-0.02 Kilograms Interval -0.971 to 0.931	-0.33 Kilograms Interval -0.734 to 0.079	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) Right knee extension, Week 17	0.32 Kilograms Interval -0.442 to 1.082	0.17 Kilograms Interval -0.204 to 0.549	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) Right knee extension, Week 33	-0.02 Kilograms Interval -0.462 to 0.422	0.35 Kilograms Interval -0.926 to 1.617	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) Right knee extension, Week 49	0.06 Kilograms Interval -0.41 to 0.53	-0.20 Kilograms Interval -0.564 to 0.164	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) Left shoulder abduction, Week 17	0.02 Kilograms Interval -0.722 to 0.762	-0.39 Kilograms Interval -1.137 to 0.356	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) Left shoulder abduction, Week 33	-0.12 Kilograms Interval -0.692 to 0.452	0.29 Kilograms Interval -1.461 to 2.042	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) Left shoulder abduction, Week 49	0.06 Kilograms Interval -0.718 to 0.838	-0.39 Kilograms Interval -1.346 to 0.564	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) Right shoulder abduction, Week 17	0.14 Kilograms Interval -0.82 to 1.1	0 Kilograms Interval -0.568 to 0.568	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) Right shoulder abduction, Week 33	0.36 Kilograms Interval -0.226 to 0.946	0.28 Kilograms Interval -1.244 to 1.807	—	—
Change From Baseline on Muscle Strength at Weeks 17, 33 and 49 in Pre-specified Subset (Baseline 4SC >8 Seconds) Right shoulder abduction, Week 49	0.32 Kilograms Interval -0.357 to 0.997	-0.17 Kilograms Interval -1.132 to 0.787	—	—

SECONDARY outcome

Timeframe: Baseline, Weeks 17, 33 and 49

Population: This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of time points.

The whole thigh muscle volume was measured by the proton density weighted sequence with magnetic resonance imaging (MRI) which was used to segment the entire thigh region into 3 primary regions for volumetric measure including 1) muscle; 2) inter/intra-muscular fat, 3) subcutaneous fat. MMRM was used to analyze the percent change from baseline for domagrozumab compared to placebo. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.

Outcome measures

Measure	Placebo n=40 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg n=80 Participants Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Percent Change From Baseline in Whole Thigh Muscle Volume as Compared to Placebo by Weeks 17, 33 and 49 Week 17	0.979 Percent change of thigh muscle volume Standard Error 1.062	3.924 Percent change of thigh muscle volume Standard Error 0.871	—	—
Percent Change From Baseline in Whole Thigh Muscle Volume as Compared to Placebo by Weeks 17, 33 and 49 Week 33	1.380 Percent change of thigh muscle volume Standard Error 1.349	4.298 Percent change of thigh muscle volume Standard Error 1.043	—	—
Percent Change From Baseline in Whole Thigh Muscle Volume as Compared to Placebo by Weeks 17, 33 and 49 Week 49	-0.802 Percent change of thigh muscle volume Standard Error 1.623	3.285 Percent change of thigh muscle volume Standard Error 1.220	—	—

SECONDARY outcome

Timeframe: Baseline, Weeks 17, 33 and 49

Population: This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.

The thigh muscle volume index was derived from the thigh muscle volume measurements as the fraction of total thigh tissue that was the lean muscle. MMRM was used to analyze the percent change from baseline for domagrozumab compared to placebo. The stratification factor, baseline result, treatment, time and treatment by time interaction were included as fixed effects in the model. Participants were included as a random effect and the model was fit with an unstructured covariance for the repeated measures.

Outcome measures

Measure	Placebo n=40 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg n=80 Participants Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Percent Change From Baseline as Compared to Placebo in Whole Thigh Muscle Volume Index by Weeks 17, 33 and 49 Week 17	-5.434 Percent change of muscle volume index Standard Error 0.844	-3.859 Percent change of muscle volume index Standard Error 0.657	—	—
Percent Change From Baseline as Compared to Placebo in Whole Thigh Muscle Volume Index by Weeks 17, 33 and 49 Week 33	-9.408 Percent change of muscle volume index Standard Error 1.121	-6.797 Percent change of muscle volume index Standard Error 0.836	—	—
Percent Change From Baseline as Compared to Placebo in Whole Thigh Muscle Volume Index by Weeks 17, 33 and 49 Week 49	-13.357 Percent change of muscle volume index Standard Error 1.358	-10.149 Percent change of muscle volume index Standard Error 0.992	—	—

SECONDARY outcome

Timeframe: Baseline, Weeks 17, 33, 49 and 97

Population: This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of time points.

The whole thigh muscle volume was measured by the proton density weighted sequence with magnetic resonance imaging (MRI) which was used to segment the entire thigh region into 3 primary regions for volumetric measure including 1) muscle; 2) inter/intra-muscular fat, 3) subcutaneous fat.

Outcome measures

Measure	Placebo n=41 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg n=39 Participants Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg n=40 Participants Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Change From Baseline in Whole Thigh Muscle Volume Through Week 97 Muscle volume, Week 17	36292.279 Cubic centimeters Interval 14495.696 to 58088.862	26292.475 Cubic centimeters Interval 5063.52 to 47521.43	5624.962 Cubic centimeters Interval -11939.656 to 23189.58	—
Change From Baseline in Whole Thigh Muscle Volume Through Week 97 Muscle volume, Week 33	37646.693 Cubic centimeters Interval 8267.121 to 67026.264	37037.651 Cubic centimeters Interval 10407.019 to 63668.283	12682.521 Cubic centimeters Interval -13221.92 to 38586.962	—
Change From Baseline in Whole Thigh Muscle Volume Through Week 97 Muscle volume, Week 49	37184.268 Cubic centimeters Interval 1604.89 to 72763.647	25360.797 Cubic centimeters Interval -7334.654 to 58056.247	-13438.274 Cubic centimeters Interval -45986.13 to 19109.581	—
Change From Baseline in Whole Thigh Muscle Volume Through Week 97 Muscle volume, Week 97	22715.921 Cubic centimeters Interval -47151.367 to 92583.21	-42588.405 Cubic centimeters Interval -101774.836 to 16598.025	-13903.138 Cubic centimeters Interval -85620.463 to 57814.187	—

SECONDARY outcome

Timeframe: Baseline, Weeks 17, 33, 49 and 97

Population: This analysis population included all participants randomized and who had received at least 1 dose of randomized treatment. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of time points.

The thigh muscle volume index was derived from the thigh muscle volume measurements as the fraction of total thigh tissue that was the lean muscle.

Outcome measures

Measure	Placebo n=41 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg n=39 Participants Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg n=40 Participants Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Change From Baseline in Whole Thigh Muscle Volume Index Through Week 97 Week 17	-1.866 Percent of whole thign volume Interval -2.805 to -0.927	-2.302 Percent of whole thign volume Interval -3.159 to -1.445	-3.049 Percent of whole thign volume Interval -4.158 to -1.94	—
Change From Baseline in Whole Thigh Muscle Volume Index Through Week 97 Week 33	-4.151 Percent of whole thign volume Interval -5.629 to -2.672	-3.706 Percent of whole thign volume Interval -5.016 to -2.396	-5.582 Percent of whole thign volume Interval -7.016 to -4.149	—
Change From Baseline in Whole Thigh Muscle Volume Index Through Week 97 Week 49	-5.750 Percent of whole thign volume Interval -7.582 to -3.917	-6.529 Percent of whole thign volume Interval -8.333 to -4.726	-7.818 Percent of whole thign volume Interval -9.743 to -5.893	—
Change From Baseline in Whole Thigh Muscle Volume Index Through Week 97 Week 97	-12.130 Percent of whole thign volume Interval -16.597 to -7.662	-14.861 Percent of whole thign volume Interval -19.379 to -10.344	-14.906 Percent of whole thign volume Interval -19.042 to -10.769	—

SECONDARY outcome

Timeframe: Predose on Day 1 of Week 1

Population: This analysis population included all enrolled participants in whom at least 1 GDF-8 concentration value was reported. Participants without contributing to the summary statistics are excluded below.

GDF-8, also called myostatin, is the target of domagrozumab. C0(GDF-8) was observed directly from data.

Outcome measures

Measure	Placebo n=40 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg n=39 Participants Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg n=39 Participants Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Concentration of Growth Differentiation Factor 8 (GDF-8) at Time 0 (Pre-dose),(C0(GDF-8) )	0.3187 Nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 38773	0.4557 Nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 6787	0.5052 Nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 7405	—

SECONDARY outcome

Timeframe: Every 4 weeks on dosing day (at predose, end of 2-hour infusion and 6 hours since start of infusion) from Week 1 to Week 48

Population: This analysis population included all enrolled participants in Sequences 1 and 2 in whom at least 1 GDF-8 concentration value was reported. Participants without contributing to the summary statistics are excluded below.

GDF-8, also called myostatin, is the target of domagrozumab. Ctrough,(GDF-8) was observed directly from data.

Outcome measures

Measure	Placebo n=78 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg n=76 Participants Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg n=75 Participants Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Trough Serum Concentration of GDF-8 (Ctrough,(GDF-8)) for Participants Receiving Domagrozumab in Period 1	4.540 ng/mL Geometric Coefficient of Variation 43	6.257 ng/mL Geometric Coefficient of Variation 42	7.449 ng/mL Geometric Coefficient of Variation 40	—

SECONDARY outcome

Timeframe: Every 4 weeks on dosing day (predose, end of 2-hour infusion and 6 hours since start of infusion) from Week 49 to Week 96

Population: This analysis population included all enrolled participants in Sequence 3 and in whom at least 1 GDF-8 concentration value was reported. Participants without contributing to the summary statistics are excluded below.

GDF-8, also called myostatin, is the target of domagrozumab. Ctrough,(GDF-8) was observed directly from data.

Outcome measures

Measure	Placebo n=37 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg n=30 Participants Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg n=21 Participants Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Ctrough,(GDF-8) for Participants of Sequence 3 in Period 2	5.572 ng/mL Geometric Coefficient of Variation 36	7.776 ng/mL Geometric Coefficient of Variation 45	8.383 ng/mL Geometric Coefficient of Variation 53	—

SECONDARY outcome

Timeframe: Every 4 weeks on dosing day (predose, end of 2-hour infusion and 6 hours since start of infusion) from Week 1 to Week 96 for Sequence 1; from Week 1 to Week 48 for Sequence 2; from Week 49 to Week 96 for Sequence 3

Population: This analysis population included all participants who received at least 1 dose of domagrozumab and in whom at least 1 concentration value was reported. Participants without contributing to the summary statistics are excluded below. Number analyzed refers to number of participants evaluable for specified rows of timepoints.

Ctrough was observed directly from data.

Outcome measures

Measure	Placebo n=41 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg n=39 Participants Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg n=38 Participants Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab Week 93	380.2 Microgram per milliliter (ug/mL) Geometric Coefficient of Variation 17	—	418.4 Microgram per milliliter (ug/mL) Geometric Coefficient of Variation 33	—
Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab Week 1	—	75.3 Microgram per milliliter (ug/mL) Geometric Coefficient of Variation NA This is individual Ctrough value. Geometric coefficient of variation is not applicable.	—	—
Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab Week 5	18.66 Microgram per milliliter (ug/mL) Geometric Coefficient of Variation 28	19.26 Microgram per milliliter (ug/mL) Geometric Coefficient of Variation 48	—	—
Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab Week 9	25.11 Microgram per milliliter (ug/mL) Geometric Coefficient of Variation 32	27.95 Microgram per milliliter (ug/mL) Geometric Coefficient of Variation 28	—	—
Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab Week 13	30.36 Microgram per milliliter (ug/mL) Geometric Coefficient of Variation 28	31.98 Microgram per milliliter (ug/mL) Geometric Coefficient of Variation 39	—	—
Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab Week 17	31.36 Microgram per milliliter (ug/mL) Geometric Coefficient of Variation 30	35.08 Microgram per milliliter (ug/mL) Geometric Coefficient of Variation 33	—	—
Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab Week 21	89.57 Microgram per milliliter (ug/mL) Geometric Coefficient of Variation 43	97.5 Microgram per milliliter (ug/mL) Geometric Coefficient of Variation 32	—	—
Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab Week 25	122.2 Microgram per milliliter (ug/mL) Geometric Coefficient of Variation 25	129.4 Microgram per milliliter (ug/mL) Geometric Coefficient of Variation 28	—	—
Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab Week 29	131.4 Microgram per milliliter (ug/mL) Geometric Coefficient of Variation 26	140.4 Microgram per milliliter (ug/mL) Geometric Coefficient of Variation 31	—	—
Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab Week 33	130.9 Microgram per milliliter (ug/mL) Geometric Coefficient of Variation 36	148.2 Microgram per milliliter (ug/mL) Geometric Coefficient of Variation 32	—	—
Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab Week 37	227.5 Microgram per milliliter (ug/mL) Geometric Coefficient of Variation 33	250.7 Microgram per milliliter (ug/mL) Geometric Coefficient of Variation 44	—	—
Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab Week 41	260.9 Microgram per milliliter (ug/mL) Geometric Coefficient of Variation 31	284.5 Microgram per milliliter (ug/mL) Geometric Coefficient of Variation 29	—	—
Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab Week 45	295.7 Microgram per milliliter (ug/mL) Geometric Coefficient of Variation 32	323.4 Microgram per milliliter (ug/mL) Geometric Coefficient of Variation 22	—	—
Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab Week 49	289.1 Microgram per milliliter (ug/mL) Geometric Coefficient of Variation 31	—	—	—
Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab Week 53	307.3 Microgram per milliliter (ug/mL) Geometric Coefficient of Variation 29	—	25.72 Microgram per milliliter (ug/mL) Geometric Coefficient of Variation 36	—
Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab Week 57	331.3 Microgram per milliliter (ug/mL) Geometric Coefficient of Variation 29	—	39.9 Microgram per milliliter (ug/mL) Geometric Coefficient of Variation 31	—
Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab Week 61	327.6 Microgram per milliliter (ug/mL) Geometric Coefficient of Variation 34	—	42.62 Microgram per milliliter (ug/mL) Geometric Coefficient of Variation 46	—
Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab Week 65	315.4 Microgram per milliliter (ug/mL) Geometric Coefficient of Variation 39	—	48.39 Microgram per milliliter (ug/mL) Geometric Coefficient of Variation 39	—
Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab Week 69	315.7 Microgram per milliliter (ug/mL) Geometric Coefficient of Variation 28	—	139.5 Microgram per milliliter (ug/mL) Geometric Coefficient of Variation 47	—
Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab Week 73	333.8 Microgram per milliliter (ug/mL) Geometric Coefficient of Variation 34	—	168.1 Microgram per milliliter (ug/mL) Geometric Coefficient of Variation 30	—
Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab Week 77	309.6 Microgram per milliliter (ug/mL) Geometric Coefficient of Variation 51	—	185.9 Microgram per milliliter (ug/mL) Geometric Coefficient of Variation 27	—
Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab Week 81	340.5 Microgram per milliliter (ug/mL) Geometric Coefficient of Variation 26	—	201.2 Microgram per milliliter (ug/mL) Geometric Coefficient of Variation 30	—
Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab Week 85	367 Microgram per milliliter (ug/mL) Geometric Coefficient of Variation 27	—	314.6 Microgram per milliliter (ug/mL) Geometric Coefficient of Variation 32	—
Trough (Pre-dose) Serum Concentration (Ctrough) of Domagrozumab Week 89	352.9 Microgram per milliliter (ug/mL) Geometric Coefficient of Variation 26	—	367.4 Microgram per milliliter (ug/mL) Geometric Coefficient of Variation 33	—

SECONDARY outcome

Timeframe: Every 4 weeks on dosing day (predose, end of 2-hour infusion and 6 hours since start of infusion) from Week 1 to Week 96 for Sequence 1; from Week 1 to Week 48 for Sequence 2; from Week 49 to Week 96 for Sequence 3

Population: Data were not collected and analyzed due to study early termination.

Cmax was observed directly from data.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Every 4 weeks on dosing day (predose, end of 2-hour infusion and 6 hours since start of infusion) from Week 1 to Week 96 for Sequence 1; from Week 1 to Week 48 for Sequence 2; from Week 49 to Week 96 for Sequence 3

Population: Data were not collected and analyzed due to study early termination.

Tmax was observed directly from the data.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At predose, end of 2-hour infusion and 6 hours since start of infusion at Week 45

Population: Data were not collected and analyzed due to study early termination.

t1/2 was calculated by Loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Participants in Sequence 2 received the last dose of domagrozumab at Week 45.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At predose, end of 2-hour infusion,6 hours and 168 hours since start of infusion on Weeks 1, 13, 17, 29, 33 and 45

Population: This analysis population included participants who were among the first 12 participants enrolled in the study, had received at least 1 dose of domagrozumab and in whom at least 1 of the PK parameters of interest was calculated. Participants without contributing to the summary statistics are excluded below.

The dosing interval tau was 672 hours (4 weeks). AUCtau was obtained by linear/log trapezoidal method. The AUCtau was assessed to fully characterize PK data and it was only assessed on the first 12 participants enrolled in the study who were required to complete additional PK visits.

Outcome measures

Measure	Placebo n=2 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg n=5 Participants Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Area Under the Serum Concentration-time Curve Over the Dosing Interval Tau (AUCtau) of Domagrozumab Week 1	26500 Microgram*hour per milliliter (ug*hr/mL) Interval 21700.0 to 31300.0	26300 Microgram*hour per milliliter (ug*hr/mL) Interval 14700.0 to 31000.0	—	—
Area Under the Serum Concentration-time Curve Over the Dosing Interval Tau (AUCtau) of Domagrozumab Week 13	34650 Microgram*hour per milliliter (ug*hr/mL) Interval 29500.0 to 39800.0	40500 Microgram*hour per milliliter (ug*hr/mL) Interval 32300.0 to 50900.0	—	—
Area Under the Serum Concentration-time Curve Over the Dosing Interval Tau (AUCtau) of Domagrozumab Week 17	120500 Microgram*hour per milliliter (ug*hr/mL) Interval 102000.0 to 139000.0	117000 Microgram*hour per milliliter (ug*hr/mL) Interval 109000.0 to 128000.0	—	—
Area Under the Serum Concentration-time Curve Over the Dosing Interval Tau (AUCtau) of Domagrozumab Week 29	152000 Microgram*hour per milliliter (ug*hr/mL) Interval 129000.0 to 175000.0	195500 Microgram*hour per milliliter (ug*hr/mL) Interval 149000.0 to 197000.0	—	—
Area Under the Serum Concentration-time Curve Over the Dosing Interval Tau (AUCtau) of Domagrozumab Week 33	244500 Microgram*hour per milliliter (ug*hr/mL) Interval 216000.0 to 273000.0	291000 Microgram*hour per milliliter (ug*hr/mL) Interval 238000.0 to 372000.0	—	—
Area Under the Serum Concentration-time Curve Over the Dosing Interval Tau (AUCtau) of Domagrozumab Week 45	333500 Microgram*hour per milliliter (ug*hr/mL) Interval 285000.0 to 382000.0	—	—	—

SECONDARY outcome

Timeframe: At predose, end of 2-hour infusion, 6 hours and 168 hours since start of infusion on Weeks 1, 13, 17, 29, 33 and 45

Population: This analysis population included participants who were among the first 12 participants enrolled in the study, had received at least 1 dose of domagrozumab and in whom at least 1 of the PK parameters of interest was calculated. Participants without contributing to the summary statistics are excluded below.

Cav was calculated by AUCtau/tau. The Cav was assessed to fully characterize PK data and it was only assessed on the first 12 participants enrolled in the study who were required to complete additional PK visits.

Outcome measures

Measure	Placebo n=2 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg n=5 Participants Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Average Serum Concentration Over the Dosing Interval (Cav) of Domagrozumab Week 13	51.55 ug/mL Interval 43.9 to 59.2	60.3 ug/mL Interval 48.0 to 75.7	—	—
Average Serum Concentration Over the Dosing Interval (Cav) of Domagrozumab Week 1	39.45 ug/mL Interval 32.3 to 46.6	39.2 ug/mL Interval 21.9 to 46.1	—	—
Average Serum Concentration Over the Dosing Interval (Cav) of Domagrozumab Week 17	179 ug/mL Interval 151.0 to 207.0	174 ug/mL Interval 162.0 to 191.0	—	—
Average Serum Concentration Over the Dosing Interval (Cav) of Domagrozumab Week 29	226.5 ug/mL Interval 192.0 to 261.0	291 ug/mL Interval 221.0 to 293.0	—	—
Average Serum Concentration Over the Dosing Interval (Cav) of Domagrozumab Week 33	364 ug/mL Interval 322.0 to 406.0	433.5 ug/mL Interval 354.0 to 553.0	—	—
Average Serum Concentration Over the Dosing Interval (Cav) of Domagrozumab Week 45	496 ug/mL Interval 424.0 to 568.0	—	—	—

SECONDARY outcome

Timeframe: At predose, end of 2-hour infusion, 6 hours and 168 hours since start of infusion on Weeks 13, 29 and 45

Population: This analysis population included participants who were among the first 12 participants enrolled in the study, had received at least 1 dose of domagrozumab and in whom at least 1 of the PK parameters of interest was calculated. Participants without contributing to the summary statistics are excluded below.

CL was calculated by Dose/AUCtau. The CL was assessed to fully characterize PK data and it was only assessed on the first 12 participants enrolled in the study who were required to complete additional PK visits.

Outcome measures

Measure	Placebo n=2 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg n=5 Participants Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Clearance (CL) of Domagrozumab Week 13	0.148 Milliliter/hr/kilogram(mL/hr/kg) Interval 0.126 to 0.17	0.123 Milliliter/hr/kilogram(mL/hr/kg) Interval 0.0983 to 0.155	—	—
Clearance (CL) of Domagrozumab Week 29	0.1345 Milliliter/hr/kilogram(mL/hr/kg) Interval 0.114 to 0.155	0.102 Milliliter/hr/kilogram(mL/hr/kg) Interval 0.102 to 0.134	—	—
Clearance (CL) of Domagrozumab Week 45	0.1225 Milliliter/hr/kilogram(mL/hr/kg) Interval 0.105 to 0.14	—	—	—

SECONDARY outcome

Timeframe: At predose, end of 2-hour infusion, 6 hours and 168 hours since start of infusion on Week 45

Population: Data were not collected and analyzed due to study early termination.

Vss was calculated by CL*MRT, where MRT was the mean residence time. Vss was assessed to fully characterize PK data.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, every 4 weeks from Week 5 to Week 97 visit or early termination

Population: This analysis population included all participants who received at least 1 dose of investigational drug. Number analyzed refers to the number of participants evaluable for specified rows of time points.

The criterion for positive result of ADA samples was ADA titer >=1.88.

Outcome measures

Measure	Placebo n=41 Participants Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg n=39 Participants Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg n=40 Participants Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).
Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 Week 21	0 Participants	0 Participants	—	—
Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 Week 25	0 Participants	0 Participants	—	—
Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 Baseline	0 Participants	0 Participants	—	—
Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 Week 5	0 Participants	0 Participants	—	—
Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 Week 9	0 Participants	0 Participants	—	—
Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 Week 13	0 Participants	0 Participants	—	—
Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 Week 17	0 Participants	0 Participants	—	—
Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 Week 29	0 Participants	0 Participants	—	—
Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 Week 33	0 Participants	0 Participants	—	—
Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 Week 37	0 Participants	0 Participants	—	—
Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 Week 41	0 Participants	0 Participants	—	—
Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 Week 45	0 Participants	0 Participants	—	—
Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 Week 49	0 Participants	0 Participants	0 Participants	—
Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 Week 53	0 Participants	—	0 Participants	—
Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 Week 57	0 Participants	—	0 Participants	—
Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 Week 61	0 Participants	—	0 Participants	—
Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 Week 65	0 Participants	—	1 Participants	—
Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 Week 69	0 Participants	—	0 Participants	—
Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 Week 73	0 Participants	—	0 Participants	—
Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 Week 77	0 Participants	—	0 Participants	—
Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 Week 81	0 Participants	—	0 Participants	—
Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 Week 85	0 Participants	—	0 Participants	—
Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 Week 89	0 Participants	—	0 Participants	—
Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 Week 93	0 Participants	—	0 Participants	—
Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 Week 97	0 Participants	0 Participants	0 Participants	—
Number of Participants With Anti-drug Antibodies (ADA) Development by Week 97 Early termination	0 Participants	0 Participants	0 Participants	—

OTHER_PRE_SPECIFIED outcome

Timeframe: At predose, end of 2-hour infusion, 6 hours and 168 hours since start of infusion on Weeks 1, 13, 17, 29, 33 and 45

Population: Data were not collected and analyzed due to study early termination.

AUClast was calculated by linear/log trapezoidal method. AUCtau was obtained by linear/log trapezoidal method. AUClast was assessed to fully characterize PK data and it was only assessed on the first 12 participants enrolled in the study who were required to complete additional PK visits.

Outcome measures

Outcome data not reported

Adverse Events

Domagrozumab 5 mg/kg, Period 1

Serious events: 1 serious events

Other events: 58 other events

Deaths: 0 deaths

Domagrozumab 20 mg/kg, Period 1

Serious events: 1 serious events

Other events: 43 other events

Deaths: 0 deaths

Domagrozumab 40 mg/kg, Period 1

Serious events: 1 serious events

Other events: 50 other events

Deaths: 0 deaths

Placebo, Period 1

Serious events: 0 serious events

Other events: 38 other events

Deaths: 0 deaths

Domagrozumab 5 mg/kg, Period 2

Serious events: 1 serious events

Other events: 29 other events

Deaths: 0 deaths

Domagrozumab 20 mg/kg, Period 2

Serious events: 1 serious events

Other events: 22 other events

Deaths: 0 deaths

Domagrozumab 40 mg/kg, Period 2

Serious events: 1 serious events

Other events: 49 other events

Deaths: 0 deaths

Placebo, Period 2

Serious events: 0 serious events

Other events: 29 other events

Deaths: 0 deaths

Serious adverse events

Measure	Domagrozumab 5 mg/kg, Period 1 n=80 participants at risk Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg, Period 1 n=78 participants at risk Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg, Period 1 n=76 participants at risk Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).	Placebo, Period 1 n=40 participants at risk Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg, Period 2 n=38 participants at risk Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 49 to Week 64 (4 doses).	Domagrozumab 20 mg/kg, Period 2 n=38 participants at risk Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 65 to Week 80 (4 doses).	Domagrozumab 40 mg/kg, Period 2 n=66 participants at risk Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 81 to Week 96 (4 doses).	Placebo, Period 2 n=37 participants at risk Participants received placebo from Week 49 to Week 96.
Infections and infestations Appendicitis	1.2% 1/80 • Number of events 1 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/78 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/76 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/40 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/38 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/38 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/66 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/37 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Injury, poisoning and procedural complications Femoral neck fracture	0.00% 0/80 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/78 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/76 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/40 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/38 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/38 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	1.5% 1/66 • Number of events 1 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/37 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Injury, poisoning and procedural complications Femur fracture	0.00% 0/80 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/78 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/76 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/40 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	2.6% 1/38 • Number of events 1 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/38 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/66 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/37 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Investigations Troponin increased	0.00% 0/80 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/78 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/76 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/40 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/38 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	2.6% 1/38 • Number of events 1 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/66 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/37 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Nervous system disorders Superior sagittal sinus thrombosis	0.00% 0/80 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	1.3% 1/78 • Number of events 1 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/76 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/40 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/38 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/38 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/66 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/37 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Psychiatric disorders Anxiety	0.00% 0/80 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/78 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	1.3% 1/76 • Number of events 1 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/40 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/38 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/38 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/66 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/37 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.

Other adverse events

Measure	Domagrozumab 5 mg/kg, Period 1 n=80 participants at risk Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 1 to Week 16 (4 doses).	Domagrozumab 20 mg/kg, Period 1 n=78 participants at risk Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 17 to Week 32 (4 doses).	Domagrozumab 40 mg/kg, Period 1 n=76 participants at risk Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 33 to Week 48 (4 doses).	Placebo, Period 1 n=40 participants at risk Participants received placebo from Week 1 to Week 48.	Domagrozumab 5 mg/kg, Period 2 n=38 participants at risk Participants received domagrozumab at a dose of 5 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 49 to Week 64 (4 doses).	Domagrozumab 20 mg/kg, Period 2 n=38 participants at risk Participants received domagrozumab at a dose of 20 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 65 to Week 80 (4 doses).	Domagrozumab 40 mg/kg, Period 2 n=66 participants at risk Participants received domagrozumab at a dose of 40 mg/kg over 2 hours by intravenous infusion every 4 weeks from Week 81 to Week 96 (4 doses).	Placebo, Period 2 n=37 participants at risk Participants received placebo from Week 49 to Week 96.
Gastrointestinal disorders Abdominal pain	3.8% 3/80 • Number of events 3 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	1.3% 1/78 • Number of events 8 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	1.3% 1/76 • Number of events 1 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	7.5% 3/40 • Number of events 3 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/38 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	2.6% 1/38 • Number of events 1 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/66 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/37 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Gastrointestinal disorders Abdominal pain upper	3.8% 3/80 • Number of events 6 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	3.8% 3/78 • Number of events 4 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	3.9% 3/76 • Number of events 4 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	10.0% 4/40 • Number of events 5 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	5.3% 2/38 • Number of events 2 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	5.3% 2/38 • Number of events 2 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	4.5% 3/66 • Number of events 6 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	2.7% 1/37 • Number of events 1 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Gastrointestinal disorders Constipation	2.5% 2/80 • Number of events 2 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/78 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	2.6% 2/76 • Number of events 2 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	10.0% 4/40 • Number of events 5 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/38 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/38 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	4.5% 3/66 • Number of events 3 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	2.7% 1/37 • Number of events 1 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Gastrointestinal disorders Diarrhoea	3.8% 3/80 • Number of events 3 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	2.6% 2/78 • Number of events 3 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	2.6% 2/76 • Number of events 2 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	17.5% 7/40 • Number of events 10 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	7.9% 3/38 • Number of events 4 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/38 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	10.6% 7/66 • Number of events 9 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	13.5% 5/37 • Number of events 6 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Gastrointestinal disorders Nausea	3.8% 3/80 • Number of events 3 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	1.3% 1/78 • Number of events 1 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/76 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	12.5% 5/40 • Number of events 5 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/38 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	2.6% 1/38 • Number of events 1 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	1.5% 1/66 • Number of events 1 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	2.7% 1/37 • Number of events 1 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Gastrointestinal disorders Vomiting	10.0% 8/80 • Number of events 9 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	7.7% 6/78 • Number of events 7 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	7.9% 6/76 • Number of events 7 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	22.5% 9/40 • Number of events 13 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	7.9% 3/38 • Number of events 3 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	2.6% 1/38 • Number of events 1 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	6.1% 4/66 • Number of events 4 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	21.6% 8/37 • Number of events 13 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
General disorders Chest pain	0.00% 0/80 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/78 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	3.9% 3/76 • Number of events 3 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	7.5% 3/40 • Number of events 3 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/38 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	2.6% 1/38 • Number of events 2 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	1.5% 1/66 • Number of events 1 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/37 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
General disorders Fatigue	3.8% 3/80 • Number of events 6 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	1.3% 1/78 • Number of events 2 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	1.3% 1/76 • Number of events 1 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	7.5% 3/40 • Number of events 5 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	5.3% 2/38 • Number of events 2 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/38 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	1.5% 1/66 • Number of events 1 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/37 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
General disorders Gait inability	2.5% 2/80 • Number of events 2 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	2.6% 2/78 • Number of events 2 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	1.3% 1/76 • Number of events 1 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	12.5% 5/40 • Number of events 5 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	2.6% 1/38 • Number of events 1 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	5.3% 2/38 • Number of events 2 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	4.5% 3/66 • Number of events 3 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	16.2% 6/37 • Number of events 6 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
General disorders Infusion site swelling	1.2% 1/80 • Number of events 1 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/78 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/76 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	2.5% 1/40 • Number of events 2 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/38 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/38 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	4.5% 3/66 • Number of events 3 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	5.4% 2/37 • Number of events 2 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
General disorders Pain	1.2% 1/80 • Number of events 1 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	1.3% 1/78 • Number of events 1 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/76 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	5.0% 2/40 • Number of events 3 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/38 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	5.3% 2/38 • Number of events 2 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/66 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/37 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
General disorders Pyrexia	7.5% 6/80 • Number of events 9 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	7.7% 6/78 • Number of events 6 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	6.6% 5/76 • Number of events 5 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	22.5% 9/40 • Number of events 15 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	5.3% 2/38 • Number of events 2 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	2.6% 1/38 • Number of events 1 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	9.1% 6/66 • Number of events 8 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	5.4% 2/37 • Number of events 2 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Infections and infestations Ear infection	3.8% 3/80 • Number of events 3 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/78 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	2.6% 2/76 • Number of events 2 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	5.0% 2/40 • Number of events 2 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/38 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	2.6% 1/38 • Number of events 1 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	6.1% 4/66 • Number of events 4 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	2.7% 1/37 • Number of events 1 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Infections and infestations Gastroenteritis	2.5% 2/80 • Number of events 2 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	1.3% 1/78 • Number of events 1 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	2.6% 2/76 • Number of events 2 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	7.5% 3/40 • Number of events 3 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/38 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	2.6% 1/38 • Number of events 1 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	4.5% 3/66 • Number of events 4 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/37 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Infections and infestations Hordeolum	0.00% 0/80 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/78 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/76 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	2.5% 1/40 • Number of events 1 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	5.3% 2/38 • Number of events 3 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	2.6% 1/38 • Number of events 2 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/66 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/37 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Infections and infestations Influenza	1.2% 1/80 • Number of events 1 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/78 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	2.6% 2/76 • Number of events 2 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	5.0% 2/40 • Number of events 2 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/38 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/38 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	9.1% 6/66 • Number of events 6 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	8.1% 3/37 • Number of events 3 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Infections and infestations Lower respiratory tract infection	0.00% 0/80 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/78 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/76 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/40 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/38 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/38 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/66 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	5.4% 2/37 • Number of events 2 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Infections and infestations Nasopharyngitis	20.0% 16/80 • Number of events 18 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	16.7% 13/78 • Number of events 14 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	10.5% 8/76 • Number of events 10 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	27.5% 11/40 • Number of events 21 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	15.8% 6/38 • Number of events 6 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	7.9% 3/38 • Number of events 5 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	12.1% 8/66 • Number of events 11 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	24.3% 9/37 • Number of events 12 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Infections and infestations Upper resiratory tract infection	7.5% 6/80 • Number of events 7 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	6.4% 5/78 • Number of events 5 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	9.2% 7/76 • Number of events 8 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	15.0% 6/40 • Number of events 13 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	13.2% 5/38 • Number of events 5 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	2.6% 1/38 • Number of events 1 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	13.6% 9/66 • Number of events 11 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	18.9% 7/37 • Number of events 7 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Injury, poisoning and procedural complications Contusion	3.8% 3/80 • Number of events 3 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	2.6% 2/78 • Number of events 2 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	3.9% 3/76 • Number of events 4 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	7.5% 3/40 • Number of events 4 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	2.6% 1/38 • Number of events 1 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/38 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	4.5% 3/66 • Number of events 4 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	8.1% 3/37 • Number of events 3 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Injury, poisoning and procedural complications Fall	27.5% 22/80 • Number of events 32 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	19.2% 15/78 • Number of events 22 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	15.8% 12/76 • Number of events 13 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	50.0% 20/40 • Number of events 43 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	23.7% 9/38 • Number of events 18 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	18.4% 7/38 • Number of events 12 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	25.8% 17/66 • Number of events 28 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	18.9% 7/37 • Number of events 13 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Injury, poisoning and procedural complications Ligment sprain	1.2% 1/80 • Number of events 1 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/78 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	1.3% 1/76 • Number of events 1 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	7.5% 3/40 • Number of events 3 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	2.6% 1/38 • Number of events 1 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/38 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	6.1% 4/66 • Number of events 4 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	10.8% 4/37 • Number of events 4 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Injury, poisoning and procedural complications Spinal compression fracture	0.00% 0/80 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	1.3% 1/78 • Number of events 1 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/76 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	10.0% 4/40 • Number of events 4 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	5.3% 2/38 • Number of events 2 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/38 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	3.0% 2/66 • Number of events 2 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	2.7% 1/37 • Number of events 1 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Musculoskeletal and connective tissue disorders Arthralgia	3.8% 3/80 • Number of events 4 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	5.1% 4/78 • Number of events 4 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	3.9% 3/76 • Number of events 3 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	15.0% 6/40 • Number of events 10 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	10.5% 4/38 • Number of events 4 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	5.3% 2/38 • Number of events 2 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	3.0% 2/66 • Number of events 2 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	2.7% 1/37 • Number of events 1 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Musculoskeletal and connective tissue disorders Back pain	6.2% 5/80 • Number of events 6 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	5.1% 4/78 • Number of events 4 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	1.3% 1/76 • Number of events 1 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	15.0% 6/40 • Number of events 7 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	2.6% 1/38 • Number of events 2 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/38 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	7.6% 5/66 • Number of events 5 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	2.7% 1/37 • Number of events 1 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/80 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/78 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/76 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	7.5% 3/40 • Number of events 3 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/38 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	2.6% 1/38 • Number of events 1 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	1.5% 1/66 • Number of events 1 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/37 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/80 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	1.3% 1/78 • Number of events 1 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	1.3% 1/76 • Number of events 1 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	7.5% 3/40 • Number of events 3 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/38 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/38 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	1.5% 1/66 • Number of events 1 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/37 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Musculoskeletal and connective tissue disorders Scoliosis	0.00% 0/80 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/78 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	1.3% 1/76 • Number of events 1 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/40 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	5.3% 2/38 • Number of events 2 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/38 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/66 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/37 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Musculoskeletal and connective tissue disorders Tendon disorder	0.00% 0/80 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/78 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/76 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/40 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/38 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/38 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/66 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	5.4% 2/37 • Number of events 2 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Nervous system disorders Headache	13.8% 11/80 • Number of events 18 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	7.7% 6/78 • Number of events 9 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	7.9% 6/76 • Number of events 10 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	35.0% 14/40 • Number of events 24 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	10.5% 4/38 • Number of events 5 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	13.2% 5/38 • Number of events 7 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	16.7% 11/66 • Number of events 20 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	10.8% 4/37 • Number of events 5 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Musculoskeletal and connective tissue disorders Pain in extremity	6.2% 5/80 • Number of events 6 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	3.8% 3/78 • Number of events 3 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	3.9% 3/76 • Number of events 3 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	17.5% 7/40 • Number of events 9 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	13.2% 5/38 • Number of events 5 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	7.9% 3/38 • Number of events 3 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	6.1% 4/66 • Number of events 5 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	8.1% 3/37 • Number of events 3 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Respiratory, thoracic and mediastinal disorders Cough	7.5% 6/80 • Number of events 6 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	1.3% 1/78 • Number of events 1 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	5.3% 4/76 • Number of events 4 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	7.5% 3/40 • Number of events 3 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	7.9% 3/38 • Number of events 3 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	10.5% 4/38 • Number of events 4 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	15.2% 10/66 • Number of events 13 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	10.8% 4/37 • Number of events 5 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Respiratory, thoracic and mediastinal disorders Epistaxis	7.5% 6/80 • Number of events 9 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	9.0% 7/78 • Number of events 14 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	3.9% 3/76 • Number of events 14 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	10.0% 4/40 • Number of events 5 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	5.3% 2/38 • Number of events 3 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/38 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	4.5% 3/66 • Number of events 14 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	8.1% 3/37 • Number of events 13 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Respiratory, thoracic and mediastinal disorders Nasal congestion	3.8% 3/80 • Number of events 3 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	6.4% 5/78 • Number of events 5 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	7.9% 6/76 • Number of events 6 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	15.0% 6/40 • Number of events 8 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	2.6% 1/38 • Number of events 1 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/38 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	12.1% 8/66 • Number of events 10 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	2.7% 1/37 • Number of events 1 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	3.8% 3/80 • Number of events 3 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/78 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	3.9% 3/76 • Number of events 3 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	12.5% 5/40 • Number of events 6 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	2.6% 1/38 • Number of events 1 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	5.3% 2/38 • Number of events 2 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	6.1% 4/66 • Number of events 5 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	8.1% 3/37 • Number of events 4 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	5.0% 4/80 • Number of events 5 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	3.8% 3/78 • Number of events 3 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/76 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	15.0% 6/40 • Number of events 6 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/38 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	2.6% 1/38 • Number of events 1 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	10.6% 7/66 • Number of events 9 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	8.1% 3/37 • Number of events 3 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Respiratory, thoracic and mediastinal disorders Sleep apnoea syndrome	0.00% 0/80 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/78 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/76 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/40 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	5.3% 2/38 • Number of events 2 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/38 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/66 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/37 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Skin and subcutaneous tissue disorders Dermatitis contact	0.00% 0/80 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/78 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/76 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/40 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	2.6% 1/38 • Number of events 1 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/38 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/66 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	5.4% 2/37 • Number of events 2 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Skin and subcutaneous tissue disorders Erythema	1.2% 1/80 • Number of events 1 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/78 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	1.3% 1/76 • Number of events 1 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	2.5% 1/40 • Number of events 1 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/38 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/38 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	1.5% 1/66 • Number of events 1 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	5.4% 2/37 • Number of events 3 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Skin and subcutaneous tissue disorders Rash	2.5% 2/80 • Number of events 2 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	1.3% 1/78 • Number of events 1 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	1.3% 1/76 • Number of events 1 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	15.0% 6/40 • Number of events 6 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/38 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	5.3% 2/38 • Number of events 2 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	7.6% 5/66 • Number of events 6 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	0.00% 0/37 • 105 weeks The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.

Additional Information

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Results disclosure agreements

• Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
• Publication restrictions are in place

Restriction type: OTHER