Trial Outcomes & Findings for An Open-label Extension Study To Evaluate Safety Of PF-06252616 In Boys With Duchenne Muscular Dystrophy (NCT NCT02907619)

Last Updated: 2020-11-23

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 or usage. Treatment-related AEs were determined by the investigator. The number of participants with dose reduced or temporary discontinuation due to both all-causality and treatment-related AEs are presented below.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

59 participants

Primary outcome timeframe

2 Years

Results posted on

2020-11-23

Participant Flow

Study B5161004 was an open-label extension (OLE) to study B5161002. The parent study B5161002 was a Phase 2, randomized, 2-period, blinded, placebo controlled study to evaluate the safety, efficacy, PK and PD of domagrozumab administered to ambulatory boys diagnosed with DMD.

Participant milestones

Participant milestones
Measure	Sequence 1 In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 2 In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 3 In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
Overall Study STARTED	19	20	20
Overall Study Received Treatment	19	20	20
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	19	20	20

Reasons for withdrawal

Reasons for withdrawal
Measure	Sequence 1 In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 2 In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 3 In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.
Overall Study Study terminated by sponsor	18	18	19
Overall Study Death	0	0	1
Overall Study Withdrawal by Subject	1	1	0
Overall Study Other	0	1	0

Baseline Characteristics

An Open-label Extension Study To Evaluate Safety Of PF-06252616 In Boys With Duchenne Muscular Dystrophy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sequence 1 n=19 Participants In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 2 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 3 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Total n=59 Participants Total of all reporting groups
Age, Categorical <=18 years	19 Participants n=5 Participants	20 Participants n=7 Participants	20 Participants n=5 Participants	59 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	9.1 years STANDARD_DEVIATION 1.0 • n=5 Participants	10.2 years STANDARD_DEVIATION 0.9 • n=7 Participants	10.4 years STANDARD_DEVIATION 1.1 • n=5 Participants	9.9 years STANDARD_DEVIATION 1.1 • 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	19 Participants n=5 Participants	20 Participants n=7 Participants	20 Participants n=5 Participants	59 Participants n=4 Participants
Race/Ethnicity, Customized White	18 Participants n=5 Participants	17 Participants n=7 Participants	18 Participants n=5 Participants	53 Participants n=4 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	5 Participants n=4 Participants
Race/Ethnicity, Customized Other	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants

PRIMARY outcome

Timeframe: 2 Years

Population: The analysis population included all participants who had received at least 1 dose of study medication in current study B5161004.

Outcome measures

Outcome measures
Measure	Sequence 1 n=19 Participants In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 2 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 3 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Total n=59 Participants Sum of all participants in the study B5161004
Number of Participants With Dose Reduced or Temporary Discontinuation Due to AEs Due to All-causality AEs	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Dose Reduced or Temporary Discontinuation Due to AEs Due to Treatment-related AEs	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: 2 Years

Population: The analysis population included all participants who had received at least 1 dose of study medication in current study B5161004.

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 or usage. 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. The number of participants with severe all-causality and treatment-related TEAEs are presented below.

Outcome measures

Outcome measures
Measure	Sequence 1 n=19 Participants In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 2 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 3 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Total n=59 Participants Sum of all participants in the study B5161004
Number of Participants With Severe Treatment-Emergent Adverse Events (TEAEs) All-Causality TEAEs	3 Participants	0 Participants	1 Participants	4 Participants
Number of Participants With Severe Treatment-Emergent Adverse Events (TEAEs) Treatment-Related TEAEs	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: 2 Years

Population: The analysis population included all participants who had received at least 1 dose of study medication in current study B5161004.

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 or usage. TEAEs were AEs occurred following the start of treatment or AEs increasing in severity during treatment. Treatment-related TEAEs were determined by the investigator. The number of participants who discontinued from the study due to both all-causality and treatment-related TEAEs are presented below.

Outcome measures

Outcome measures
Measure	Sequence 1 n=19 Participants In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 2 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 3 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Total n=59 Participants Sum of all participants in the study B5161004
Number of Participants Who Discontinued From the Study Due to TEAEs Due to All-causality AEs	0 Participants	0 Participants	1 Participants	1 Participants
Number of Participants Who Discontinued From the Study Due to TEAEs Due to Treatment-related AEs	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: 2 Years

Population: Analysis population included all participants who had received at least 1 dose of study medication in current study B5161004. 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 and absolute monocytes. Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. (ULN=Upper Limit of Normal; LLN=Lower Limit of Normal).

Outcome measures

Outcome measures
Measure	Sequence 1 n=19 Participants In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 2 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 3 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Total n=59 Participants Sum of all participants in the study B5161004
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Hematology Hemoglobin <0.8 × LLN	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Hematology Hematocrit <0.8 × LLN	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Hematology RBC count <0.8 × LLN	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Hematology Platelets <0.5 × LLN	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Hematology Platelets >1.75 × ULN	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Hematology RBC Morphology >0	0 Participants	1 Participants	0 Participants	1 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Hematology WBC count <0.6 × LLN	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Hematology WBC count >1.5 × ULN	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Hematology Absolute Lymphocytes <0.8 × LLN	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Hematology Absolute lymphocytes >1.2 × ULN	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Hematology Absolute atypical lymphocytes >0	1 Participants	—	—	1 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Hematology Absolute total neutrophils <0.8 × LLN	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Hematology Absolute total neutrophils >1.2 × ULN	3 Participants	1 Participants	2 Participants	6 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Hematology Absolute total neutrophil count <1.35 × 10^3/mcL	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Hematology Absolute total neutrophil count >8.15 × 10^3/mcL	6 Participants	1 Participants	5 Participants	12 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Hematology Absolute band cells >0.27 × 10^3/mcL	0 Participants	—	—	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Hematology Absolute basophils >1.2 × ULN	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Hematology Absolute eosinophils >1.2 × ULN	1 Participants	0 Participants	1 Participants	2 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Hematology Absolute monocytes >1.2 × ULN	1 Participants	0 Participants	1 Participants	2 Participants

PRIMARY outcome

Timeframe: 2 Years

Population: Analysis population included all participants who had received at least 1 dose of study medication in current study B5161004.

Coagulation evaluation included activated partial thromboplastin time (aPTT) and prothrombin time (PT). (ULN=Upper Limit of Normal). Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004.

Outcome measures

Outcome measures
Measure	Sequence 1 n=19 Participants In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 2 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 3 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Total n=59 Participants Sum of all participants in the study B5161004
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Coagulation aPTT >1.1 x ULN	0 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Coagulation PT >1.1 x ULN	1 Participants	0 Participants	1 Participants	2 Participants

PRIMARY outcome

Timeframe: 2 Years

Population: Analysis population included all participants who had received at least 1 dose of study medication in current study B5161004.

Liver function evaluation included: total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), alkaline phosphatase, total protein, albumin and glutamate dehydrogenase. Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. (LLN=Lower Limit of Normal; ULN=Upper Limit of Normal).

Outcome measures

Outcome measures
Measure	Sequence 1 n=19 Participants In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 2 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 3 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Total n=59 Participants Sum of all participants in the study B5161004
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Liver Function Albumin >1.2 x ULN	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Liver Function Total Bilirubin >1.5 x ULN	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Liver Function AST >3.0 x ULN	16 Participants	16 Participants	15 Participants	47 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Liver Function ALT >3.0 x ULN	19 Participants	18 Participants	19 Participants	56 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Liver Function GGT >3.0 x ULN	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Liver Function Alkaline Phosphatase >3.0 x ULN	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Liver Function Total Protein <0.8 x LLN	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Liver Function Total Protein >1.2 x ULN	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Liver Function Albumin <0.8 x LLN	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Liver Function Glutamate Dehydrogenase >1.0 x ULN	0 Participants	0 Participants	1 Participants	1 Participants

PRIMARY outcome

Timeframe: 2 Years

Population: Analysis population included all participants who had received at least 1 dose of study medication in current study B5161004.

Renal function evaluation included: blood urea nitrogen (BUN), creatinine and uric acid. Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. (ULN=Upper Limit of Normal).

Outcome measures

Outcome measures
Measure	Sequence 1 n=19 Participants In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 2 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 3 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Total n=59 Participants Sum of all participants in the study B5161004
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Renal Function Blood Urea Nitrogen (BUN) >1.3 x ULN	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Renal Function Creatinine >1.3 x ULN	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Renal Function Uric Acid >1.2 x ULN	1 Participants	0 Participants	0 Participants	1 Participants

PRIMARY outcome

Timeframe: 2 Years

Population: Analysis population included all participants who had received at least 1 dose of study medication in current study B5161004.

Electrolytes evaluation included: sodium, potassium, chloride, calcium, phosphate and bicarbonate. Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. (LLN=Lower Limit of Normal, ULN=Upper Limit of Normal).

Outcome measures

Outcome measures
Measure	Sequence 1 n=19 Participants In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 2 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 3 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Total n=59 Participants Sum of all participants in the study B5161004
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Electrolytes Calcium >1.1 x ULN	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Electrolytes Sodium <0.95 x LLN	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Electrolytes Sodium >1.05 x ULN	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Electrolytes Potassium <0.9 x LLN	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Electrolytes Potassium >1.1 x ULN	1 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Electrolytes Chloride <0.9 x LLN	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Electrolytes Chloride >1.1 x ULN	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Electrolytes Calcium <0.9 x LLN	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Electrolytes Phosphate <0.8 x LLN	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Electrolytes Phosphate >1.2 x ULN	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Electrolytes Bicarbonate (venous) <0.9 x LLN	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Electrolytes Bicarbonate (venous) >1.1 x ULN	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: 2 Years

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. Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. (LLN=Lower Limit of Normal, ULN=Upper Limit of Normal).

Outcome measures

Outcome measures
Measure	Sequence 1 n=19 Participants In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 2 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 3 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Total n=59 Participants Sum of all participants in the study B5161004
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Hormones LH(12years - <13 years) <0.3 mIU/mL	0 Participants	5 Participants	8 Participants	13 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Hormones FSH (9years - <11 years) >4.50mIU/mL	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Hormones FSH (13 years - <14 years) >10.80mIU/mL	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Hormones T4 (free) <0.8 x LLN	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Hormones T4 (free) >1.2 x ULN	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Hormones TSH <0.8 x LLN	0 Participants	1 Participants	0 Participants	1 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Hormones TSH >1.2 x ULN	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Hormones LH (7years - <9 years) <0.3mIU/mL	0 Participants	—	—	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Hormones LH(7years - <9 years) >2.8mIU/mL	0 Participants	—	—	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Hormones LH (9years - <11 years) <0.3mIU/mL	8 Participants	5 Participants	3 Participants	16 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Hormones LH (9years - <11 years) >2.8mIU/mL	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Hormones LH (11years - <12 years) <0.3mIU/mL	2 Participants	3 Participants	2 Participants	7 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Hormones LH (11years - <12 years) >1.8mIU/mL	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Hormones LH(12years - <13 years) >4.0mIU/mL	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Hormones LH(13years - <14 years) <0.3mIU/mL	1 Participants	0 Participants	1 Participants	2 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Hormones LH(13years - <14 years) >6.0mIU/mL	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Hormones FSH(7years - <9 years) >4.10mIU/mL	0 Participants	—	—	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Hormones FSH (11years - <12 years) <0.40mIU/mL	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Hormones FSH (11years - <12 years) >8.90mIU/mL	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Hormones FSH (12years - <13 years) <0.50mIU/mL	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Hormones FSH (12years - <13 years) >10.50mIU/mL	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Hormones FSH (13years - <14 years) <0.70mIU/mL	1 Participants	0 Participants	1 Participants	2 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Hormones Androstenedione (7 - <10years) <3 ng/dL	0 Participants	0 Participants	2 Participants	2 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Hormones Androstenedione(7 - <10 years) >31 ng/dL	1 Participants	1 Participants	0 Participants	2 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Hormones Androstenedione (10 - <12years) <7 ng/dL	5 Participants	3 Participants	1 Participants	9 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Hormones Androstenedione (10-<12years) >41 ng/dL	1 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Hormones Androstenedione (12 - <14years) <11 ng/dL	1 Participants	4 Participants	6 Participants	11 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Hormones Androstenedione (12 - <14years) >64 ng/dL	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: 2 Years

Clinical chemistry evaluation included glucose, creatine kinase (CK), troponin I, amylase, iron binding capacity, unsaturated iron binding capacity, transferrin saturation, iron and ferritin. Number of participants with iron abnormalities was reported in different age groups. Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. (LLN=Lower Limit of Normal, ULN=Upper Limit of Normal).

Outcome measures

Outcome measures
Measure	Sequence 1 n=19 Participants In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 2 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 3 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Total n=59 Participants Sum of all participants in the study B5161004
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Clinical Chemistry Troponin I >3.0 x ULN	4 Participants	4 Participants	1 Participants	9 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Clinical Chemistry Amylase > 1.5 x ULN	0 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Clinical Chemistry Unsaturated Iron Binding Capacity <130 mcg/dL	3 Participants	4 Participants	3 Participants	10 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Clinical Chemistry Unsaturated Iron Binding Capacity >375 mcg/dL	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Clinical Chemistry Transferrin Saturation < 20%	0 Participants	3 Participants	2 Participants	5 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Clinical Chemistry Iron 1Y<=Age<11Y >120	12 Participants	2 Participants	2 Participants	16 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Clinical Chemistry Iron 11Y<=Age<18Y <50	0 Participants	3 Participants	0 Participants	3 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Clinical Chemistry Iron 11Y<=Age<18Y >170	0 Participants	1 Participants	1 Participants	2 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Clinical Chemistry Glucose <0.6 x LLN	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Clinical Chemistry Glucose >1.5 x ULN	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Clinical Chemistry CK >2.0 x ULN	19 Participants	20 Participants	20 Participants	59 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Clinical Chemistry Iron Binding Capacity <37.6 mcg/dL	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Clinical Chemistry Transferrin Saturation > 50%	7 Participants	4 Participants	6 Participants	17 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Clinical Chemistry Iron 1Y<=Age<11Y <50	0 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Clinical Chemistry Ferritin <15 ng/mL	4 Participants	6 Participants	5 Participants	15 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Clinical Chemistry Ferritin >140 ng/mL	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: 2 Years

Urinalysis Microscopy included: urine red blood cell (RBC), urine white blood cell (WBC), urine uric acid crystals, urine calcium oxalate crystals, urine amorphous crystals, urine bacteria, urine microscopic exam. Urinalysis Dipstick included: urine pH, urine glucose, urine ketones, urine protein, urine blood/hemoglobin, urine nitrite, urine leukocyte esterase. Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004.

Outcome measures

Outcome measures
Measure	Sequence 1 n=19 Participants In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 2 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 3 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Total n=59 Participants Sum of all participants in the study B5161004
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Urinalysis Microscopy - Urine RBC >=20	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Urinalysis Microscopy - Urine WBC >=20	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Urinalysis Microscopy-Urine Uric Acid Crystals -Present	1 Participants	—	—	1 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Urinalysis Microscopy-Urine Calcium Oxalate Crystals -Present	4 Participants	7 Participants	4 Participants	15 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Urinalysis Microscopy-Urine Amorphous Crystals -Present	3 Participants	3 Participants	2 Participants	8 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Urinalysis Microscopy - Urine Bacteria >20	0 Participants	0 Participants	—	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Urinalysis Microscopy-Urine Microscopic Exam -Positive	8 Participants	11 Participants	7 Participants	26 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Urinalysis Dipstick - Urine pH <4.5	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Urinalysis Dipstick - Urine pH >8	0 Participants	1 Participants	0 Participants	1 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Urinalysis Dipstick - urine glucose >=1	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Urinalysis Dipstick - urine ketones >=1	0 Participants	1 Participants	1 Participants	2 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Urinalysis Dipstick - urine protein >=1	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Urinalysis Dipstick - urine blood/hemoglobin >=1	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Urinalysis Dipstick - Urine nitrite >=1	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Urinalysis Dipstick - Urine Leukocyte Esterase >=1	0 Participants	1 Participants	0 Participants	1 Participants

PRIMARY outcome

Timeframe: 2 Years

Population: Analysis population included all participants who had received at least 1 dose of study medication in current study B5161004 and who were evaluable for this outcome measure.

Number of participants with blood detected in fecal samples is presented. Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. (ULN=Upper Limit of Normal).

Outcome measures

Outcome measures
Measure	Sequence 1 n=19 Participants In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 2 n=17 Participants In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 3 n=17 Participants In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Total n=53 Participants Sum of all participants in the study B5161004
Number of Participants With Laboratory Test Abnormalities (Without Regard to B5161004 Baseline Abnormality) - Fecal Blood	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Baseline, Weeks 13, 25, 37, 49, 61, 73 and 85.

Participants were asked to fast for at least 8 hours prior to collection of blood to evaluate serum iron, serum ferritin and % transferrin saturation. The unit of iron was mcg/dL; the unit of ferritin was ng/mL; the unit of %transferrin saturation was %. Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. Week 1 was counted starting from the study treatment in study B5161004.

Outcome measures

Outcome measures
Measure	Sequence 1 n=19 Participants In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 2 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 3 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Total n=59 Participants Sum of all participants in the study B5161004
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline Iron-Week 73: 144 - <200	0 Participants	1 Participants	0 Participants	1 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline Iron-Week 85: 144 - <200	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline Iron - Baseline: <120	13 Participants	18 Participants	10 Participants	41 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline Iron - Baseline: 120 - <144	3 Participants	2 Participants	6 Participants	11 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline Iron - Baseline: 144 - <200	3 Participants	0 Participants	4 Participants	7 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline Iron - Baseline: >=200	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline Iron - Week 13: <120	10 Participants	15 Participants	9 Participants	34 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline Iron - Week 13: 120 - <144	3 Participants	0 Participants	7 Participants	10 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline Iron - Week 13: 144 - <200	2 Participants	1 Participants	1 Participants	4 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline Iron - Week 13: >=200	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline Iron - Week 25: <120	8 Participants	10 Participants	8 Participants	26 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline Iron - Week 25: 120 - <144	3 Participants	0 Participants	4 Participants	7 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline Iron - Week 25: 144 - <200	1 Participants	2 Participants	1 Participants	4 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline Iron - Week 25: >=200	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline Iron-Week 37: <120	5 Participants	6 Participants	10 Participants	21 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline Iron-Week 37: 120 - <144	1 Participants	3 Participants	2 Participants	6 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline Iron-Week 37: 144 - <200	2 Participants	0 Participants	0 Participants	2 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline Iron-Week 37: >=200	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline Iron-Week 49: <120	6 Participants	3 Participants	6 Participants	15 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline Iron-Week 49: 120 - <144	1 Participants	0 Participants	1 Participants	2 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline Iron-Week 49: 144 - <200	0 Participants	3 Participants	1 Participants	4 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline Iron-Week 49: >=200	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline Iron-Week 61: <120	1 Participants	2 Participants	2 Participants	5 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline Iron-Week 61: 120 - <144	1 Participants	1 Participants	1 Participants	3 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline Iron-Week 61: 144 - <200	1 Participants	1 Participants	0 Participants	2 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline Iron-Week 61: >=200	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline Iron-Week 73: <120	1 Participants	1 Participants	2 Participants	4 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline Ferritin-Week 73: >=140	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline Ferritin-Week 85: <140	0 Participants	1 Participants	1 Participants	2 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline Ferritin-Week 85: >=140	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline Iron-Week 73: 120 - <144	1 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline Iron-Week 73: >=200	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline Iron-Week 85: <120	0 Participants	1 Participants	1 Participants	2 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline Iron-Week 85: 120 - <144	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline Iron-Week 85: >=200	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline Ferritin-Baseline: <140	19 Participants	20 Participants	20 Participants	59 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline Ferritin-Baseline: >=140	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline Ferritin-Week 13: <140	14 Participants	17 Participants	16 Participants	47 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline Ferritin-Week 13: >=140	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline Ferritin-Week 25: <140	12 Participants	12 Participants	13 Participants	37 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline %Transferrin Saturation - Baseline: <45	15 Participants	20 Participants	18 Participants	53 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline %Transferrin Saturation Baseline: 45 - <50	3 Participants	0 Participants	1 Participants	4 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline %Transferrin Saturation Baseline: 50 - <69	0 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline %Transferrin Saturation Baseline: >=69	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline Ferritin-Week 25: >=140	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline Ferritin-Week 37: <140	7 Participants	9 Participants	12 Participants	28 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline Ferritin-Week 37: >=140	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline Ferritin-Week 49: <140	7 Participants	6 Participants	8 Participants	21 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline Ferritin-Week 49: >=140	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline Ferritin-Week 61: <140	2 Participants	4 Participants	3 Participants	9 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline Ferritin-Week 61: >=140	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline Ferritin-Week 73: <140	2 Participants	2 Participants	2 Participants	6 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline %Transferrin Saturation Week 13: <45	12 Participants	15 Participants	13 Participants	40 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline %Transferrin Saturation Week 13: 45 - <50	1 Participants	0 Participants	1 Participants	2 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline %Transferrin Saturation Week 13: 50 - <69	2 Participants	1 Participants	2 Participants	5 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline %Transferrin Saturation Week 13: >=69	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline %Transferrin Saturation Week 25: <45	9 Participants	10 Participants	9 Participants	28 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline %Transferrin Saturation Week 25: 45 - <50	0 Participants	1 Participants	2 Participants	3 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline %Transferrin Saturation Week 25: 50 - <69	1 Participants	1 Participants	2 Participants	4 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline %Transferrin Saturation Week 25: >=69	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline %Transferrin Saturation Week 37: <45	4 Participants	6 Participants	11 Participants	21 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline %Transferrin Saturation Week 37: 45 - <50	1 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline %Transferrin Saturation Week 37: 50 - <69	1 Participants	1 Participants	1 Participants	3 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline %Transferrin Saturation Week 37: >=69	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline %Transferrin Saturation Week 49: <45	6 Participants	4 Participants	6 Participants	16 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline %Transferrin Saturation Week 49: 45 - <50	0 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline %Transferrin Saturation Week 49: 50 - <69	1 Participants	2 Participants	1 Participants	4 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline %Transferrin Saturation Week 49: >=69	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline %Transferrin Saturation Week 61: <45	1 Participants	2 Participants	3 Participants	6 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline %Transferrin Saturation Week 61: 45 - <50	0 Participants	1 Participants	0 Participants	1 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline %Transferrin Saturation Week 61: 50 - <69	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline %Transferrin Saturation Week 61: >=69	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline %Transferrin Saturation Week 73: <45	2 Participants	1 Participants	2 Participants	5 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline %Transferrin Saturation Week 73: 45 - <50	0 Participants	1 Participants	0 Participants	1 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline %Transferrin Saturation Week 73: 50 - <69	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline %Transferrin Saturation Week 73: >=69	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline %Transferrin Saturation Week 85: <45	0 Participants	1 Participants	1 Participants	2 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline %Transferrin Saturation Week 85: 45 - <50	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline %Transferrin Saturation Week 85: 50 - <69	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Data of Serum Ferritin, Serum Iron and % Transferrin Saturation Meeting Categorical Summarization Criteria - B5161004 Baseline %Transferrin Saturation Week 85: >=69	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: 2 Years

Population: Analysis population included all participants who had received at least 1 dose of study medication in current study B5161004.

Physical examinations were conducted by a physician, trained physician's assistant, or nurse practitioner as acceptable according to local regulation. A targeted nose and throat mucosal exam was performed to monitor for any signs of mucosal telangiectasias. The clinically significant physical examination results were determined by the investigator.

Outcome measures

Outcome measures
Measure	Sequence 1 n=19 Participants In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 2 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 3 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Total n=59 Participants Sum of all participants in the study B5161004
Number of Participants With Significant Results of Physical Examinations Including Nose and Throat Mucosal Examinations	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Screening, Baseline, Week 49.

Tanner staging was performed before the first dose of this study 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. Participant's Week 97 visit within study B5161002 (parent study) was collected as screening data. Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. Week 1 was counted starting from the study treatment in study B5161004.

Outcome measures

Outcome measures
Measure	Sequence 1 n=19 Participants In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 2 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 3 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Total n=59 Participants Sum of all participants in the study B5161004
Summary of Pubertal Development by Tanner Stage Public Hair, Stage 5, Baseline	0 Participants	0 Participants	0 Participants	0 Participants
Summary of Pubertal Development by Tanner Stage Public Hair, ND/NA, Week 49	0 Participants	0 Participants	0 Participants	0 Participants
Summary of Pubertal Development by Tanner Stage Penis, ND, Screening	0 Participants	1 Participants	0 Participants	1 Participants
Summary of Pubertal Development by Tanner Stage Public Hair, Stage 1, Week 49	3 Participants	3 Participants	5 Participants	11 Participants
Summary of Pubertal Development by Tanner Stage Public Hair, Stage 2 Week 49	4 Participants	3 Participants	3 Participants	10 Participants
Summary of Pubertal Development by Tanner Stage Public Hair, Not Detected (ND) Screening	0 Participants	1 Participants	0 Participants	1 Participants
Summary of Pubertal Development by Tanner Stage Public Hair, Stage 1, Screening	1 Participants	0 Participants	0 Participants	1 Participants
Summary of Pubertal Development by Tanner Stage Public Hair, Stage 2, Screening	0 Participants	0 Participants	0 Participants	0 Participants
Summary of Pubertal Development by Tanner Stage Public Hair, Stage 3, Week 49	0 Participants	0 Participants	0 Participants	0 Participants
Summary of Pubertal Development by Tanner Stage Public Hair, Stage 3, Screening	0 Participants	0 Participants	0 Participants	0 Participants
Summary of Pubertal Development by Tanner Stage Public Hair, Stage 4, Screening	0 Participants	0 Participants	0 Participants	0 Participants
Summary of Pubertal Development by Tanner Stage Public Hair, Stage 5, Screening	0 Participants	0 Participants	0 Participants	0 Participants
Summary of Pubertal Development by Tanner Stage Public Hair, ND, Baseline	1 Participants	0 Participants	0 Participants	1 Participants
Summary of Pubertal Development by Tanner Stage Public Hair, Stage 1, Baseline	12 Participants	9 Participants	12 Participants	33 Participants
Summary of Pubertal Development by Tanner Stage Public Hair, Stage 2, Baseline	5 Participants	10 Participants	8 Participants	23 Participants
Summary of Pubertal Development by Tanner Stage Public Hair, Stage 3, Baseline	1 Participants	1 Participants	0 Participants	2 Participants
Summary of Pubertal Development by Tanner Stage Public Hair, Stage 4, Baseline	0 Participants	0 Participants	0 Participants	0 Participants
Summary of Pubertal Development by Tanner Stage Public Hair, Stage 4, Week 49	0 Participants	0 Participants	0 Participants	0 Participants
Summary of Pubertal Development by Tanner Stage Public Hair, Stage 5, Week 49	0 Participants	0 Participants	0 Participants	0 Participants
Summary of Pubertal Development by Tanner Stage Penis, Stage 1, Screening	1 Participants	0 Participants	0 Participants	1 Participants
Summary of Pubertal Development by Tanner Stage Penis, Stage 2, Screening	0 Participants	0 Participants	0 Participants	0 Participants
Summary of Pubertal Development by Tanner Stage Penis, Stage 3, Screening	0 Participants	0 Participants	0 Participants	0 Participants
Summary of Pubertal Development by Tanner Stage Penis, Stage 4, Screening	0 Participants	0 Participants	0 Participants	0 Participants
Summary of Pubertal Development by Tanner Stage Penis, Stage 5, Screening	0 Participants	0 Participants	0 Participants	0 Participants
Summary of Pubertal Development by Tanner Stage Penis, ND / NA, Baseline	1 Participants	0 Participants	0 Participants	1 Participants
Summary of Pubertal Development by Tanner Stage Penis, Stage 1, Baseline	13 Participants	11 Participants	11 Participants	35 Participants
Summary of Pubertal Development by Tanner Stage Penis, Stage 2, Baseline	5 Participants	9 Participants	9 Participants	23 Participants
Summary of Pubertal Development by Tanner Stage Penis, Stage 3, Baseline	0 Participants	0 Participants	0 Participants	0 Participants
Summary of Pubertal Development by Tanner Stage Penis, Stage 4, Baseline	0 Participants	0 Participants	0 Participants	0 Participants
Summary of Pubertal Development by Tanner Stage Penis, Stage 5, Baseline	0 Participants	0 Participants	0 Participants	0 Participants
Summary of Pubertal Development by Tanner Stage Penis, ND, Week 49	0 Participants	0 Participants	0 Participants	0 Participants
Summary of Pubertal Development by Tanner Stage Penis, Stage 1, Week 49	4 Participants	2 Participants	4 Participants	10 Participants
Summary of Pubertal Development by Tanner Stage Penis, Stage 2, Week 49	3 Participants	4 Participants	3 Participants	10 Participants
Summary of Pubertal Development by Tanner Stage Penis, Stage 3, Week 49	0 Participants	0 Participants	1 Participants	1 Participants
Summary of Pubertal Development by Tanner Stage Penis, Stage 4, Week 49	0 Participants	0 Participants	0 Participants	0 Participants
Summary of Pubertal Development by Tanner Stage Penis, Stage 5, Week 49	0 Participants	0 Participants	0 Participants	0 Participants
Summary of Pubertal Development by Tanner Stage Testes, ND, Screening	0 Participants	1 Participants	0 Participants	1 Participants
Summary of Pubertal Development by Tanner Stage Testes, Stage 1, Screening	1 Participants	0 Participants	0 Participants	1 Participants
Summary of Pubertal Development by Tanner Stage Testes, Stage 2, Screening	0 Participants	0 Participants	0 Participants	0 Participants
Summary of Pubertal Development by Tanner Stage Testes, Stage 3, Screening	0 Participants	0 Participants	0 Participants	0 Participants
Summary of Pubertal Development by Tanner Stage Testes, Stage 4, Screening	0 Participants	0 Participants	0 Participants	0 Participants
Summary of Pubertal Development by Tanner Stage Testes, Stage 5, Screening	0 Participants	0 Participants	0 Participants	0 Participants
Summary of Pubertal Development by Tanner Stage Testes, ND, Baseline	1 Participants	0 Participants	0 Participants	1 Participants
Summary of Pubertal Development by Tanner Stage Testes, Stage 1, Baseline	13 Participants	10 Participants	10 Participants	33 Participants
Summary of Pubertal Development by Tanner Stage Testes, Stage 2, Baseline	5 Participants	9 Participants	10 Participants	24 Participants
Summary of Pubertal Development by Tanner Stage Testes, Stage 3, Baseline	0 Participants	1 Participants	0 Participants	1 Participants
Summary of Pubertal Development by Tanner Stage Testes, Stage 4, Baseline	0 Participants	0 Participants	0 Participants	0 Participants
Summary of Pubertal Development by Tanner Stage Testes, Stage 5, Baseline	0 Participants	0 Participants	0 Participants	0 Participants
Summary of Pubertal Development by Tanner Stage Testes, ND, Week 49	0 Participants	0 Participants	0 Participants	0 Participants
Summary of Pubertal Development by Tanner Stage Testes, Stage 1, Week 49	4 Participants	4 Participants	1 Participants	9 Participants
Summary of Pubertal Development by Tanner Stage Testes, Stage 2, Week 49	3 Participants	2 Participants	6 Participants	11 Participants
Summary of Pubertal Development by Tanner Stage Testes, Stage 3, Week 49	0 Participants	0 Participants	1 Participants	1 Participants
Summary of Pubertal Development by Tanner Stage Testes, Stage 4, Week 49	0 Participants	0 Participants	0 Participants	0 Participants
Summary of Pubertal Development by Tanner Stage Testes, Stage 5, Week 49	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Screening, Baseline, Week 49.

Testicular volume was used to monitor pubertal development. Participant's Week 97 visit within Study B5161002 (parent study) was collected as screening data in current study. Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. Week 1 was counted starting from the study treatment in study B5161004.

Outcome measures

Outcome measures
Measure	Sequence 1 n=18 Participants In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 2 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 3 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Total n=58 Participants Sum of all participants in the study B5161004
Summary of Testicular Volume Left Testis Volume - Screening	3.0 Milliliter Standard Deviation NA This was individual testicular volume. Standard deviation was not applicable.	—	—	3.0 Milliliter Standard Deviation NA This was individual testicular volume. Standard deviation was not applicable.
Summary of Testicular Volume Left Testis Volume - Baseline	2.7 Milliliter Standard Deviation 1.07	2.8 Milliliter Standard Deviation 1.06	2.7 Milliliter Standard Deviation 1.63	2.7 Milliliter Standard Deviation 1.27
Summary of Testicular Volume Left Testis Volume - Week 49	2.6 Milliliter Standard Deviation 0.98	2.5 Milliliter Standard Deviation 0.55	3.8 Milliliter Standard Deviation 3.41	3.0 Milliliter Standard Deviation 2.19
Summary of Testicular Volume Right Testis Volume - Screening	3.0 Milliliter Standard Deviation NA This was individual testicular volume. Standard deviation was not applicable.	—	—	3.0 Milliliter Standard Deviation NA This was individual testicular volume. Standard deviation was not applicable.
Summary of Testicular Volume Right Testis Volume - Baseline	2.7 Milliliter Standard Deviation 1.03	2.8 Milliliter Standard Deviation 0.97	2.6 Milliliter Standard Deviation 1.64	2.7 Milliliter Standard Deviation 1.23
Summary of Testicular Volume Right Testis Volume - Week 49	2.6 Milliliter Standard Deviation 0.98	2.5 Milliliter Standard Deviation 0.55	3.6 Milliliter Standard Deviation 3.46	3.0 Milliliter Standard Deviation 2.20

PRIMARY outcome

Timeframe: 2 Years

The number of participants pre-dose supine blood pressure and pulse rate meeting categorical summarization criteria are recorded in this table. Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. (DBP=diastolic blood pressure, SBP=systolic blood pressure; The unit for blood pressure is: mmHg, the unit for pulse rate is: beats per minute \[BPM\])

Outcome measures

Outcome measures
Measure	Sequence 1 n=19 Participants In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 2 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 3 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Total n=59 Participants Sum of all participants in the study B5161004
Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria - B5161004 Baseline Supine SBP - Observed Values <70+2×Age (2-10years)	1 Participants	1 Participants	0 Participants	2 Participants
Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria - B5161004 Baseline Supine SBP - Observed Values < 90 (11-17 years)	0 Participants	1 Participants	1 Participants	2 Participants
Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria - B5161004 Baseline Maximum Increase From Baseline in Supine SBP >=30	1 Participants	0 Participants	3 Participants	4 Participants
Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria - B5161004 Baseline Maximum Decrease From Baseline in Supine SBP >=30	0 Participants	1 Participants	0 Participants	1 Participants
Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria - B5161004 Baseline Supine DBP - Observed Values <50 (<18 years)	1 Participants	1 Participants	2 Participants	4 Participants
Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria - B5161004 Baseline Maximum Increase From Baseline in Supine DBP >=20	3 Participants	1 Participants	5 Participants	9 Participants
Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria - B5161004 Baseline Maximum Decrease From Baseline in Supine DBP >=20	0 Participants	2 Participants	0 Participants	2 Participants
Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria - B5161004 Baseline Supine Pulse Rate-Observed Values<40BPM(<18 years)	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria - B5161004 Baseline Supine Pulse Rate-Observed Values>120BPM(<18years)	2 Participants	0 Participants	1 Participants	3 Participants

PRIMARY outcome

Timeframe: 2 Years

Population: Analysis population included all participants who had received at least 1 dose of study medication in current study B5161004.

The number of participants with data of pre-dose supine blood pressure meeting categorical summarization were recorded in this table. Overall Baseline was defined as the last pre-dose assessment prior to the first day of dosing in study B5161002. (DBP=diastolic blood pressure, SBP=systolic blood pressure; The unit for blood pressure is: mmHg).

Outcome measures

Outcome measures
Measure	Sequence 1 n=19 Participants In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 2 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 3 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Total n=59 Participants Sum of all participants in the study B5161004
Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria - Overall Baseline Maximum Increase From Baseline in Supine DBP >=20	8 Participants	8 Participants	10 Participants	26 Participants
Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria - Overall Baseline Maximum Increase From Baseline in Supine SBP >=30	2 Participants	6 Participants	2 Participants	10 Participants
Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria - Overall Baseline Maximum Decrease From Baseline in Supine SBP >=30	0 Participants	3 Participants	4 Participants	7 Participants
Number of Participants With Post-Baseline Vital Signs Data Meeting Categorical Summarization Criteria - Overall Baseline Maximum Decrease From Baseline in Supine DBP >=20	4 Participants	4 Participants	8 Participants	16 Participants

PRIMARY outcome

Timeframe: 2 Years

Population: Analysis population included all participants who had received at least 1 dose of study medication in current study B5161004 and who were evaluable for this outcome measure.

QTcF=QT/(60/Hour)\*\*(1/3). Means of replicates were used in the calculations. QT=time between the start of the Q wave and the end of the T wave in the heart's electrical cycle; QTcF=corrected QT (Fridericia correction). All scheduled ECGs were performed after the participant had rested quietly for at least 10 minutes in a supine position. Baseline was defined as the average of the last triplicate pre-dose measurements prior to Day 1 in B5161004.

Outcome measures

Outcome measures
Measure	Sequence 1 n=18 Participants In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 2 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 3 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Total n=58 Participants Sum of all participants in the study B5161004
Number of Participants With Post-Baseline ECG Data Meeting Categorical Summarization Criteria - B5161004 Baseline Maximum(Max)QTcF Interval-ObservedValues<450msec	18 Participants	20 Participants	18 Participants	56 Participants
Number of Participants With Post-Baseline ECG Data Meeting Categorical Summarization Criteria - B5161004 Baseline Max QTcF Interval -Observed Values450-<480msec	0 Participants	0 Participants	2 Participants	2 Participants
Number of Participants With Post-Baseline ECG Data Meeting Categorical Summarization Criteria - B5161004 Baseline Max QTcF Interval -Observed Values480-<500msec	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Post-Baseline ECG Data Meeting Categorical Summarization Criteria - B5161004 Baseline Max QTcF Interval -Observed Values>=500msec	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Post-Baseline ECG Data Meeting Categorical Summarization Criteria - B5161004 Baseline Max QTcF Interval Increase From Baseline<30msec	16 Participants	20 Participants	18 Participants	54 Participants
Number of Participants With Post-Baseline ECG Data Meeting Categorical Summarization Criteria - B5161004 Baseline Max QTcF Interval Increase From Baseline30-<60msec	2 Participants	0 Participants	0 Participants	2 Participants
Number of Participants With Post-Baseline ECG Data Meeting Categorical Summarization Criteria - B5161004 Baseline Max QTcF Interval Increase From Baseline>= 60msec	0 Participants	0 Participants	2 Participants	2 Participants

PRIMARY outcome

Timeframe: 2 Years

Population: Analysis population included all participants who had received at least 1 dose of study medication in current study B5161004.

QT=time between the start of the Q wave and the end of the T wave in the heart's electrical cycle; QTcF=corrected QT (Fridericia correction). All scheduled ECGs were performed after the participant had rested quietly for at least 10 minutes in a supine position. Overall baseline was defined as the average of the last triplicate pre-dose measurements prior to the first day of dosing in study B5161002.

Outcome measures

Outcome measures
Measure	Sequence 1 n=19 Participants In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 2 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 3 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Total n=59 Participants Sum of all participants in the study B5161004
Number of Participants With Post-Baseline ECG Data Meeting Categorical Summarization Criteria - Overall Baseline Maximum QTcF Interval Increase From Baseline <30	11 Participants	15 Participants	17 Participants	43 Participants
Number of Participants With Post-Baseline ECG Data Meeting Categorical Summarization Criteria - Overall Baseline Max-QTcF Interval IncreaseFromBaseline30-<60msec	7 Participants	5 Participants	1 Participants	13 Participants
Number of Participants With Post-Baseline ECG Data Meeting Categorical Summarization Criteria - Overall Baseline Maximum QTcF Interval Increase From Baseline >=60	1 Participants	0 Participants	2 Participants	3 Participants

PRIMARY outcome

Timeframe: Screening and Week 49.

Liver Magnetic Resonance Imaging (MRIs) were sent to an independent central radiology imaging facility for calculation of the average R2\* value which was used to monitor for iron accumulation in the liver. Mean R2\* values had been used in the calculations. Normal: R2\* \<= 75 Hz at 1.5 T or \<=139 Hz at 3.0 T; Above Normal: R2\* \> 75 Hz and \<= 190 Hz at 1.5 T or R2\* \> 139 Hz and \<= 369 Hz at 3.0 T Mild overload: R2\* \> 190 Hz at 1.5 T or R2\* \> 369 Hz at 3.0 T Data from participant's Week 93 visit in Study B5161002 (parent study) were used for screening in the current study.

Outcome measures

Outcome measures
Measure	Sequence 1 n=19 Participants In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 2 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 3 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Total n=59 Participants Sum of all participants in the study B5161004
Number of Participants With Iron Accumulation Data Meeting Categorical Summarization Criteria Screening - Normal	19 Participants	20 Participants	20 Participants	59 Participants
Number of Participants With Iron Accumulation Data Meeting Categorical Summarization Criteria Screening - Above Normal	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Iron Accumulation Data Meeting Categorical Summarization Criteria Screening - Mild Overload	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Iron Accumulation Data Meeting Categorical Summarization Criteria Week 49 - Normal	7 Participants	6 Participants	8 Participants	21 Participants
Number of Participants With Iron Accumulation Data Meeting Categorical Summarization Criteria Week 49 - Above Normal	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Iron Accumulation Data Meeting Categorical Summarization Criteria Week 49 - Mild Overload	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Iron Accumulation Data Meeting Categorical Summarization Criteria Total - Normal	19 Participants	20 Participants	20 Participants	59 Participants
Number of Participants With Iron Accumulation Data Meeting Categorical Summarization Criteria Total - Above Normal	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Iron Accumulation Data Meeting Categorical Summarization Criteria Total - Mild Overload	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Baseline and Week 49.

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 imaging (MRI) or echocardiography. The same method of cardiac imaging was used consistently for each participant. Cardiac MRIs were read by a central imaging vendor, while echocardiograms were read locally (at each site). The table presents the results from cardiac MRIs. Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. Week 1 was counted starting from the study treatment in study B5161004.

Outcome measures

Outcome measures
Measure	Sequence 1 n=19 Participants In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 2 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 3 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Total n=59 Participants Sum of all participants in the study B5161004
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) by Cardiac MRI - B5161004 Baseline Baseline - Observed Values	56.000 Ratio of Ejected Blood Standard Deviation 5.6569	60.750 Ratio of Ejected Blood Standard Deviation 2.2174	62.400 Ratio of Ejected Blood Standard Deviation 5.6833	60.636 Ratio of Ejected Blood Standard Deviation 4.8430
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) by Cardiac MRI - B5161004 Baseline Week 49 - Change From Baseline	-3.000 Ratio of Ejected Blood Standard Deviation NA Standard deviation was not applicable for individual value.	—	-1.500 Ratio of Ejected Blood Standard Deviation 4.9497	-2.000 Ratio of Ejected Blood Standard Deviation 3.6056

PRIMARY outcome

Timeframe: Baseline, Weeks 49, 97, 146.

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 imaging (MRI) or echocardiography. The same method of cardiac imaging was used consistently for each participant. Cardiac MRIs were read by a central imaging vendor, while echocardiograms were read locally (at each site). The table presents the results from cardiac MRIs. Overall baseline was defined as the last pre-dose assessment prior to the first day of dosing in study B5161002. Week 1 was counted starting from the study treatment in study B5161002.

Outcome measures

Outcome measures
Measure	Sequence 1 n=19 Participants In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 2 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 3 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Total n=59 Participants Sum of all participants in the study B5161004
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) by Cardiac MRI - Overall Baseline Baseline - Observed Values	66.000 Ratio of Ejected Blood Standard Deviation 8.4853	61.250 Ratio of Ejected Blood Standard Deviation 3.5000	61.333 Ratio of Ejected Blood Standard Deviation 5.3541	62.083 Ratio of Ejected Blood Standard Deviation 5.1250
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) by Cardiac MRI - Overall Baseline Week 49 - Change From Baseline	-11.000 Ratio of Ejected Blood Standard Deviation 2.8284	-3.500 Ratio of Ejected Blood Standard Deviation 1.9149	0.000 Ratio of Ejected Blood Standard Deviation 7.4498	-3.273 Ratio of Ejected Blood Standard Deviation 6.4357
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) by Cardiac MRI - Overall Baseline Week 97 - Change From Baseline	-10.000 Ratio of Ejected Blood Standard Deviation 2.8284	-0.500 Ratio of Ejected Blood Standard Deviation 2.8868	-0.800 Ratio of Ejected Blood Standard Deviation 6.5727	-2.364 Ratio of Ejected Blood Standard Deviation 5.9038
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) by Cardiac MRI - Overall Baseline Week 146 - Change From Baseline	-15.000 Ratio of Ejected Blood Standard Deviation NA Standard deviation was not applicable for individual value.	—	3.500 Ratio of Ejected Blood Standard Deviation 0.7071	-2.667 Ratio of Ejected Blood Standard Deviation 10.6927

PRIMARY outcome

Timeframe: Baseline, Week 49.

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 imaging (MRI) or echocardiography. The same method of cardiac imaging was used consistently for each participant. Cardiac MRIs were read by a central imaging vendor, while echocardiograms were read locally (at each site). The table presents the results from echocardiograms. Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. Week 1 was counted starting from the study treatment in study B5161004.

Outcome measures

Outcome measures
Measure	Sequence 1 n=19 Participants In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 2 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 3 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Total n=59 Participants Sum of all participants in the study B5161004
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) by Echocardiogram - B5161004 Baseline Baseline - Observed Values	60.359 Ratio of Ejected Blood Standard Deviation 3.7545	62.461 Ratio of Ejected Blood Standard Deviation 6.0180	62.543 Ratio of Ejected Blood Standard Deviation 5.3731	61.740 Ratio of Ejected Blood Standard Deviation 5.1170
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) by Echocardiogram - B5161004 Baseline Week 49 - Change From Baseline	-0.400 Ratio of Ejected Blood Standard Deviation 5.0334	-3.900 Ratio of Ejected Blood Standard Deviation 8.9252	2.200 Ratio of Ejected Blood Standard Deviation 7.6056	-0.900 Ratio of Ejected Blood Standard Deviation 7.4580

PRIMARY outcome

Timeframe: Baseline, Weeks 49, 97, 146.

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 imaging (MRI) or echocardiography. The same method of cardiac imaging was used consistently for each participant. Cardiac MRIs were read by a central imaging vendor, while echocardiograms were read locally (at each site). The table presents the results from echocardiograms. Overall baseline was defined as the last pre-dose assessment prior to the first day of dosing in study B5161002. Week 1 was counted starting from the study treatment in study B5161002.

Outcome measures

Outcome measures
Measure	Sequence 1 n=19 Participants In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 2 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 3 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Total n=59 Participants Sum of all participants in the study B5161004
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) by Echocardiogram - Overall Baseline Week 97 - Change From Baseline	-2.929 Ratio of Ejected Blood Standard Deviation 5.4060	-1.810 Ratio of Ejected Blood Standard Deviation 6.1321	-1.414 Ratio of Ejected Blood Standard Deviation 6.4799	-2.097 Ratio of Ejected Blood Standard Deviation 5.8924
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) by Echocardiogram - Overall Baseline Baseline - Observed Values	63.288 Ratio of Ejected Blood Standard Deviation 4.3743	64.094 Ratio of Ejected Blood Standard Deviation 4.3025	64.073 Ratio of Ejected Blood Standard Deviation 4.5848	63.802 Ratio of Ejected Blood Standard Deviation 4.3395
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) by Echocardiogram - Overall Baseline Week 49 - Change From Baseline	-0.171 Ratio of Ejected Blood Standard Deviation 5.7432	-1.040 Ratio of Ejected Blood Standard Deviation 4.8861	-0.213 Ratio of Ejected Blood Standard Deviation 6.1487	-0.462 Ratio of Ejected Blood Standard Deviation 5.5142
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) by Echocardiogram - Overall Baseline Week 146 - Change From Baseline	-1.240 Ratio of Ejected Blood Standard Deviation 2.3416	-4.833 Ratio of Ejected Blood Standard Deviation 4.2151	-1.440 Ratio of Ejected Blood Standard Deviation 11.6993	-2.650 Ratio of Ejected Blood Standard Deviation 6.8514

PRIMARY outcome

Timeframe: Baseline and Week 49.

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. Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. Week 1 was counted starting from the study treatment in study B5161004.

Outcome measures

Outcome measures
Measure	Sequence 1 n=19 Participants In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 2 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 3 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Total n=59 Participants Sum of all participants in the study B5161004
Bone Age to Chronological Age Ratio Week 49	0.74 Ratio Standard Deviation 0.197	0.65 Ratio Standard Deviation 0.157	0.70 Ratio Standard Deviation 0.172	0.70 Ratio Standard Deviation 0.172
Bone Age to Chronological Age Ratio Baseline	0.76 Ratio Standard Deviation 0.213	0.74 Ratio Standard Deviation 0.195	0.81 Ratio Standard Deviation 0.177	0.77 Ratio Standard Deviation 0.194

PRIMARY outcome

Timeframe: Screening (Week 97 visit within parent study B5161002) and Week 49

Bone mineral density (BMD) was monitored by dual energy x-ray absorptiometry (DXA). DXA scans were obtained to evaluate bone mineral density of the spine and whole body without head. 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

Outcome measures
Measure	Sequence 1 n=19 Participants In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 2 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 3 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Total n=59 Participants Sum of all participants in the study B5161004
Whole Body and Spine DXA: Bone Mineral Density Z-Score, Height Adjusted Over Time Body Without Head - Screening	-1.936367 Standard Deviations Standard Deviation 1.1544544	-1.956332 Standard Deviations Standard Deviation 1.3561294	-1.872619 Standard Deviations Standard Deviation 1.4843432	-1.921525 Standard Deviations Standard Deviation 1.3187696
Whole Body and Spine DXA: Bone Mineral Density Z-Score, Height Adjusted Over Time Anterior Posterior Spine Total L1 to L4 -Screening	-0.687659 Standard Deviations Standard Deviation 0.9152662	-0.587384 Standard Deviations Standard Deviation 1.0241266	-0.561789 Standard Deviations Standard Deviation 1.0285799	-0.613225 Standard Deviations Standard Deviation 0.9731687
Whole Body and Spine DXA: Bone Mineral Density Z-Score, Height Adjusted Over Time Anterior Posterior Spine Total L1 to L4 - Week 49	-0.131374 Standard Deviations Standard Deviation 0.9251749	-0.435384 Standard Deviations Standard Deviation 0.5747293	-0.152854 Standard Deviations Standard Deviation 1.7877768	-0.227106 Standard Deviations Standard Deviation 1.1053887
Whole Body and Spine DXA: Bone Mineral Density Z-Score, Height Adjusted Over Time Body Without Head - Week 49	-1.789347 Standard Deviations Standard Deviation 1.1738270	-1.943538 Standard Deviations Standard Deviation 1.6839551	-1.455670 Standard Deviations Standard Deviation 1.5655008	-1.732667 Standard Deviations Standard Deviation 1.4033563

PRIMARY outcome

Timeframe: 2 Years

Population: Analysis population included all participants who had received at least 1 dose of study medication in current study B5161004.

The Columbia Suicide Severity Rating Scale (C-SSRS) was performed to identify the risk of suicide ideation or behavior. C-SSRS was conducted with the participant's caregiver/legal guardian on the participant's behalf throughout the study, rather than administering this evaluation directly with the study participants. If at any visit the participant endorsed a 4 or 5 on the C-SSRS ideation section or reported any suicidality behavior, then an evaluation of suicide risk (risk assessment) had to be completed and the participant must have been discontinued. The significant result of C-SSRS was determined by the investigator.

Outcome measures

Outcome measures
Measure	Sequence 1 n=19 Participants In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 2 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 3 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Total n=59 Participants Sum of all participants in the study B5161004
Number of Participants With Suicidal Ideation or Suicidal Behavior Suicidal Ideation	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Suicidal Ideation or Suicidal Behavior Suicidal Behavior	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline, Weeks 13, 25, 49, 73.

Population: This analysis population included all participants who had received at least 1 dose of study medication in current study B5161004.

The 4SC quantified the time required for a participant to ascend 4 standard steps. The functional assessment of 4SC was conducted by a physiotherapist (or exercise physiologist). In order to provide optimal testing conditions and consistency in endpoint measurements, the functional assessments were completed at approximately the same time of day. Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. Week 1 was counted starting from the study treatment in study B5161004.

Outcome measures

Outcome measures
Measure	Sequence 1 n=19 Participants In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 2 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 3 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Total n=59 Participants Sum of all participants in the study B5161004
Change From Baseline on the 4 Stair Climb (4SC) - B5161004 Baseline Baseline	7.268 Seconds Interval 3.779 to 10.757	5.218 Seconds Interval 3.37 to 7.065	5.373 Seconds Interval 2.936 to 7.809	6.050 Seconds Interval 4.53 to 7.57
Change From Baseline on the 4 Stair Climb (4SC) - B5161004 Baseline Week 13	0.839 Seconds Interval -0.68 to 2.357	0.821 Seconds Interval 0.178 to 1.463	0.400 Seconds Interval -0.416 to 1.216	0.709 Seconds Interval 0.098 to 1.32
Change From Baseline on the 4 Stair Climb (4SC) - B5161004 Baseline Week 25	1.248 Seconds Interval -0.05 to 2.546	0.319 Seconds Interval -0.073 to 0.71	0.663 Seconds Interval -0.368 to 1.693	0.765 Seconds Interval 0.236 to 1.294
Change From Baseline on the 4 Stair Climb (4SC) - B5161004 Baseline Week 49	10.150 Seconds Interval -5.363 to 25.663	0.998 Seconds Interval -0.14 to 2.135	2.400 Seconds Interval -2.917 to 7.717	5.126 Seconds Interval -0.46 to 10.712
Change From Baseline on the 4 Stair Climb (4SC) - B5161004 Baseline Week 73	9.350 Seconds Insufficient number of participants to calculate a 95% Confidence Interval.	3.100 Seconds Insufficient number of participants to calculate a 95% Confidence Interval.	1.000 Seconds Insufficient number of participants to calculate a 95% Confidence Interval.	5.180 Seconds Interval -0.234 to 10.594

SECONDARY outcome

Timeframe: Baseline, Weeks 9,17,25,33,41,49,57,65,73,81,89,97,110,122,146,170.

Population: The analysis population included all participants who had received at least 1 dose of study medication in current study B5161004. 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. The functional assessment of 4SC was conducted by a physiotherapist (or exercise physiologist). In order to provide optimal testing conditions and consistency in endpoint measurements, the functional assessments were completed at approximately the same time of day. This is the overall change from baseline which included the change since enrolling in the parent study B5161002. Overall baseline was defined as the last pre-dose assessment prior to the first day of dosing in study B5161002. Week 1 was counted starting from the study treatment in study B5161002.

Outcome measures

Outcome measures
Measure	Sequence 1 n=19 Participants In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 2 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 3 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Total n=59 Participants Sum of all participants in the study B5161004
Change From Baseline on the 4SC - Overall Baseline Baseline	4.381 Seconds Interval 3.442 to 5.319	5.664 Seconds Interval 3.728 to 7.599	5.717 Seconds Interval 4.141 to 7.292	5.268 Seconds Interval 4.409 to 6.128
Change From Baseline on the 4SC - Overall Baseline Week 9	-0.096 Seconds Interval -0.582 to 0.389	0.898 Seconds Interval -0.444 to 2.24	0.879 Seconds Interval 0.103 to 1.654	0.566 Seconds Interval 0.046 to 1.085
Change From Baseline on the 4SC - Overall Baseline Week 17	0.500 Seconds Interval -0.365 to 1.365	2.270 Seconds Interval -0.898 to 5.438	1.493 Seconds Interval 0.009 to 2.977	1.390 Seconds Interval 0.309 to 2.472
Change From Baseline on the 4SC - Overall Baseline Week 25	0.427 Seconds Interval -0.385 to 1.239	2.835 Seconds Interval 0.094 to 5.576	2.836 Seconds Interval -0.775 to 6.447	2.018 Seconds Interval 0.577 to 3.458
Change From Baseline on the 4SC - Overall Baseline Week 33	1.298 Seconds Interval -1.043 to 3.639	3.713 Seconds Interval -0.573 to 7.999	1.804 Seconds Interval 0.151 to 3.457	2.280 Seconds Interval 0.63 to 3.93
Change From Baseline on the 4SC - Overall Baseline Week 41	0.920 Seconds Interval -0.665 to 2.505	3.361 Seconds Interval -1.17 to 7.892	2.217 Seconds Interval 0.192 to 4.241	2.140 Seconds Interval 0.508 to 3.773
Change From Baseline on the 4SC - Overall Baseline Week 49	0.480 Seconds Interval -0.04 to 1.0	2.391 Seconds Interval 0.151 to 4.63	1.898 Seconds Interval 0.397 to 3.399	1.567 Seconds Interval 0.704 to 2.43
Change From Baseline on the 4SC - Overall Baseline Week 57	0.712 Seconds Interval 0.129 to 1.294	3.827 Seconds Interval -0.137 to 7.791	2.914 Seconds Interval -0.289 to 6.118	2.428 Seconds Interval 0.846 to 4.01
Change From Baseline on the 4SC - Overall Baseline Week 65	1.337 Seconds Interval 0.141 to 2.533	4.259 Seconds Interval 0.138 to 8.38	2.181 Seconds Interval -1.064 to 5.426	2.601 Seconds Interval 0.941 to 4.261
Change From Baseline on the 4SC - Overall Baseline Week 73	1.561 Seconds Interval 0.066 to 3.055	3.082 Seconds Interval 0.752 to 5.412	1.849 Seconds Interval 0.178 to 3.52	2.157 Seconds Interval 1.15 to 3.164
Change From Baseline on the 4SC - Overall Baseline Week 81	1.633 Seconds Interval 0.561 to 2.704	3.006 Seconds Interval -0.084 to 6.096	2.262 Seconds Interval -0.026 to 4.55	2.270 Seconds Interval 1.087 to 3.453
Change From Baseline on the 4SC - Overall Baseline Week 89	1.687 Seconds Interval 0.68 to 2.694	2.069 Seconds Interval 0.779 to 3.359	3.182 Seconds Interval -0.296 to 6.661	2.255 Seconds Interval 1.161 to 3.349
Change From Baseline on the 4SC - Overall Baseline Week 97	2.652 Seconds Interval 0.323 to 4.981	1.874 Seconds Interval 0.562 to 3.185	1.790 Seconds Interval 0.217 to 3.363	2.156 Seconds Interval 1.123 to 3.189
Change From Baseline on the 4SC - Overall Baseline Week 110	3.811 Seconds Interval 0.071 to 7.552	2.748 Seconds Interval 0.95 to 4.547	1.806 Seconds Interval -0.435 to 4.048	2.892 Seconds Interval 1.33 to 4.453
Change From Baseline on the 4SC - Overall Baseline Week 122	3.128 Seconds Interval 0.653 to 5.603	1.781 Seconds Interval 0.76 to 2.802	1.909 Seconds Interval -0.412 to 4.229	2.318 Seconds Interval 1.259 to 3.377
Change From Baseline on the 4SC - Overall Baseline Week 146	11.933 Seconds Interval -4.591 to 28.458	2.498 Seconds Interval -1.975 to 6.97	4.034 Seconds Interval -3.016 to 11.084	6.784 Seconds Interval 0.749 to 12.819
Change From Baseline on the 4SC - Overall Baseline Week 170	10.450 Seconds Insufficient number of participants to calculate a 95% Confidence Interval.	6.150 Seconds Insufficient number of participants to calculate a 95% Confidence Interval.	2.100 Seconds Insufficient number of participants to calculate a 95% Confidence Interval.	7.060 Seconds Interval 1.542 to 12.578

SECONDARY outcome

Timeframe: Baseline, Weeks 13, 25, 49 and 73.

FVC was measured using the FVC maneuver by spirometry to evaluate respiratory muscle function. The best (largest) FVC measurement from a set of 3 was captured on the database. Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. Week 1 was counted starting from the study treatment in study B5161004.

Outcome measures

Outcome measures
Measure	Sequence 1 n=19 Participants In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 2 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 3 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Total n=59 Participants Sum of all participants in the study B5161004
Change From Baseline on the Forced Vital Capacity (FVC) - B5161004 Baseline Baseline	1.6550 Litres Interval 1.4829 to 1.8271	1.7029 Litres Interval 1.4607 to 1.9452	1.8678 Litres Interval 1.6245 to 2.111	1.7461 Litres Interval 1.6227 to 1.8694
Change From Baseline on the Forced Vital Capacity (FVC) - B5161004 Baseline Week 13	0.0344 Litres Interval -0.0355 to 0.1042	0.1106 Litres Interval -0.062 to 0.2832	0.0380 Litres Interval -0.0417 to 0.1177	0.0615 Litres Interval -0.0024 to 0.1254
Change From Baseline on the Forced Vital Capacity (FVC) - B5161004 Baseline Week 25	0.0718 Litres Interval -0.0701 to 0.2137	0.1467 Litres Interval 0.0081 to 0.2852	0.1086 Litres Interval -0.0094 to 0.2266	0.1100 Litres Interval 0.0409 to 0.1791
Change From Baseline on the Forced Vital Capacity (FVC) - B5161004 Baseline Week 49	0.2086 Litres Interval 0.0862 to 0.331	0.2633 Litres Interval -0.0621 to 0.5887	0.0671 Litres Interval -0.0385 to 0.1728	0.1755 Litres Interval 0.0794 to 0.2716
Change From Baseline on the Forced Vital Capacity (FVC) - B5161004 Baseline Week 73	0.2800 Litres Insufficient number of participants to calculate a 95% Confidence Interval.	0.3750 Litres Insufficient number of participants to calculate a 95% Confidence Interval.	0.1450 Litres Insufficient number of participants to calculate a 95% Confidence Interval.	0.2667 Litres Interval -0.0373 to 0.5707

SECONDARY outcome

Timeframe: Baseline, Weeks 9,17,25,33,41,49,57,65,73,81,89,97,110,122,146,170.

Forced vital capacity (FVC) was measured using the FVC maneuver by spirometry to evaluate respiratory muscle function. The best (largest) FVC measurement from a set of 3 was captured on the database. This is the overall change from baseline which included the change since enrolling in the parent study B5161002. Overall baseline was defined as the last pre-dose assessment prior to the first day of dosing in study B5161002. Week 1 was counted starting from the study treatment in study B5161002.

Outcome measures

Outcome measures
Measure	Sequence 1 n=19 Participants In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 2 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 3 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Total n=59 Participants Sum of all participants in the study B5161004
Change From Baseline on the FVC - Overall Baseline Week 170	0.5500 Litres Insufficient number of participants to calculate a 95% Confidence Interval.	0.2850 Litres Insufficient number of participants to calculate a 95% Confidence Interval.	0.4900 Litres Insufficient number of participants to calculate a 95% Confidence Interval.	0.4417 Litres Interval 0.195 to 0.6884
Change From Baseline on the FVC - Overall Baseline Baseline	1.3753 Litres Interval 1.2305 to 1.52	1.5810 Litres Interval 1.4256 to 1.7364	1.6265 Litres Interval 1.4322 to 1.8208	1.5302 Litres Interval 1.4353 to 1.625
Change From Baseline on the FVC - Overall Baseline Week 9	0.1205 Litres Interval 0.0093 to 0.2317	0.1089 Litres Interval -0.0307 to 0.2486	-0.0435 Litres Interval -0.1331 to 0.0461	0.0602 Litres Interval -0.0049 to 0.1253
Change From Baseline on the FVC - Overall Baseline Week 17	0.0837 Litres Interval -0.0234 to 0.1907	0.0700 Litres Interval -0.0113 to 0.1513	0.0585 Litres Interval -0.0097 to 0.1267	0.0705 Litres Interval 0.0237 to 0.1173
Change From Baseline on the FVC - Overall Baseline Week 25	0.0679 Litres Interval -0.0461 to 0.1819	0.1140 Litres Interval 0.0204 to 0.2076	-0.0135 Litres Interval -0.1276 to 0.1006	0.0559 Litres Interval -0.004 to 0.1158
Change From Baseline on the FVC - Overall Baseline Week 33	0.1463 Litres Interval 0.0379 to 0.2548	0.0740 Litres Interval -0.0414 to 0.1894	0.1100 Litres Interval 0.0425 to 0.1775	0.1095 Litres Interval 0.0553 to 0.1637
Change From Baseline on the FVC - Overall Baseline Week 41	0.1484 Litres Interval 0.0343 to 0.2625	0.1115 Litres Interval -0.0298 to 0.2528	0.1320 Litres Interval 0.0582 to 0.2058	0.1303 Litres Interval 0.0689 to 0.1918
Change From Baseline on the FVC - Overall Baseline Week 49	0.1328 Litres Interval -0.0053 to 0.2709	0.1350 Litres Interval 0.0427 to 0.2273	0.1565 Litres Interval 0.1011 to 0.2119	0.1417 Litres Interval 0.0886 to 0.1948
Change From Baseline on the FVC - Overall Baseline Week 57	0.1063 Litres Interval -0.047 to 0.2597	0.1735 Litres Interval 0.0607 to 0.2863	0.1656 Litres Interval 0.0406 to 0.2905	0.1486 Litres Interval 0.0772 to 0.22
Change From Baseline on the FVC - Overall Baseline Week 65	0.2005 Litres Interval 0.053 to 0.348	0.1830 Litres Interval 0.0959 to 0.2701	0.1726 Litres Interval 0.0647 to 0.2806	0.1853 Litres Interval 0.1225 to 0.2482
Change From Baseline on the FVC - Overall Baseline Week 73	0.1706 Litres Interval -0.0177 to 0.3588	0.1925 Litres Interval 0.0706 to 0.3144	0.1330 Litres Interval 0.0521 to 0.2139	0.1652 Litres Interval 0.0927 to 0.2376
Change From Baseline on the FVC - Overall Baseline Week 81	0.2263 Litres Interval 0.0718 to 0.3808	0.1353 Litres Interval 0.011 to 0.2595	0.2045 Litres Interval 0.1279 to 0.2811	0.1890 Litres Interval 0.1225 to 0.2554
Change From Baseline on the FVC - Overall Baseline Week 89	0.2406 Litres Interval 0.0674 to 0.4137	0.1960 Litres Interval 0.0389 to 0.3531	0.2145 Litres Interval 0.1087 to 0.3203	0.2158 Litres Interval 0.1369 to 0.2946
Change From Baseline on the FVC - Overall Baseline Week 97	0.2932 Litres Interval 0.1616 to 0.4247	0.1365 Litres Interval -0.0336 to 0.3066	0.2375 Litres Interval 0.1472 to 0.3278	0.2212 Litres Interval 0.1462 to 0.2962
Change From Baseline on the FVC - Overall Baseline Week 110	0.2781 Litres Interval 0.1373 to 0.4189	0.2256 Litres Interval 0.0736 to 0.3777	0.2407 Litres Interval 0.1167 to 0.3646	0.2483 Litres Interval 0.1734 to 0.3232
Change From Baseline on the FVC - Overall Baseline Week 122	0.2973 Litres Interval 0.0532 to 0.5413	0.3708 Litres Interval 0.2666 to 0.475	0.3221 Litres Interval 0.1436 to 0.5007	0.3305 Litres Interval 0.236 to 0.425
Change From Baseline on the FVC - Overall Baseline Week 146	0.4629 Litres Interval 0.1599 to 0.7658	0.4167 Litres Interval 0.1726 to 0.6607	0.3114 Litres Interval 0.1531 to 0.4698	0.3960 Litres Interval 0.2797 to 0.5123

SECONDARY outcome

Timeframe: Baseline, Weeks 13, 25, 49, 73.

The NSAA was a 17-item test that measured gross motor function. Each individual item was evaluated with either 0-unable to perform independently, 1-able to perform with assistance, 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). Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. Week 1 was counted starting from the study treatment in study B5161004.

Outcome measures

Outcome measures
Measure	Sequence 1 n=19 Participants In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 2 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 3 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Total n=59 Participants Sum of all participants in the study B5161004
Change From Baseline on the Northstar Ambulatory Assessment (NSAA) Score - B5161004 Baseline Baseline	16.4 Units on a Scale Interval 11.8 to 21.0	17.1 Units on a Scale Interval 11.6 to 22.6	12.9 Units on a Scale Interval 6.9 to 19.0	15.4 Units on a Scale Interval 12.5 to 18.4
Change From Baseline on the Northstar Ambulatory Assessment (NSAA) Score - B5161004 Baseline Week 13	-0.6 Units on a Scale Interval -1.3 to 0.1	-1.7 Units on a Scale Interval -3.0 to -0.4	-0.4 Units on a Scale Interval -1.6 to 0.7	-0.9 Units on a Scale Interval -1.5 to -0.3
Change From Baseline on the Northstar Ambulatory Assessment (NSAA) Score - B5161004 Baseline Week 25	-1.8 Units on a Scale Interval -3.1 to -0.5	-0.7 Units on a Scale Interval -1.6 to 0.2	-0.8 Units on a Scale Interval -2.0 to 0.5	-1.0 Units on a Scale Interval -1.7 to -0.4
Change From Baseline on the Northstar Ambulatory Assessment (NSAA) Score - B5161004 Baseline Week 49	-3.6 Units on a Scale Interval -6.9 to -0.2	-3.2 Units on a Scale Interval -5.8 to -0.6	-3.2 Units on a Scale Interval -5.6 to -0.7	-3.3 Units on a Scale Interval -4.6 to -2.0
Change From Baseline on the Northstar Ambulatory Assessment (NSAA) Score - B5161004 Baseline Week 73	-5.5 Units on a Scale Insufficient number of participants to calculate a 95% Confidence Interval.	-3.0 Units on a Scale Insufficient number of participants to calculate a 95% Confidence Interval.	-4.0 Units on a Scale Insufficient number of participants to calculate a 95% Confidence Interval.	-4.2 Units on a Scale Interval -7.4 to -1.0

SECONDARY outcome

Timeframe: Baseline, Weeks 9,17,25,33,41,49,57,65,73,81,89,97,110,122,146,170.

The NSAA was a 17-item test that measured gross motor function. Each individual item was evaluated with either 0-unable to perform independently, 1-able to perform with assistance, 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). This is the overall change from baseline which included the change since enrolling in the parent study B5161002. Overall baseline was defined as the last pre-dose assessment prior to the first day of dosing in study B5161002. Week 1 was counted starting from the study treatment in study B5161002.

Outcome measures

Outcome measures
Measure	Sequence 1 n=19 Participants In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 2 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 3 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Total n=59 Participants Sum of all participants in the study B5161004
Change From Baseline on the NSAA Score - Overall Baseline Week 146	-9.9 Units on a Scale Interval -19.7 to 0.0	-8.3 Units on a Scale Interval -13.2 to -3.5	-7.3 Units on a Scale Interval -10.1 to -4.5	-8.6 Units on a Scale Interval -11.9 to -5.3
Change From Baseline on the NSAA Score - Overall Baseline Baseline	20.8 Units on a Scale Interval 17.6 to 24.1	21.2 Units on a Scale Interval 17.2 to 25.2	19.5 Units on a Scale Interval 16.0 to 23.0	20.5 Units on a Scale Interval 18.5 to 22.5
Change From Baseline on the NSAA Score - Overall Baseline Week 9	-0.2 Units on a Scale Interval -1.3 to 1.0	0.4 Units on a Scale Interval -0.6 to 1.4	-0.8 Units on a Scale Interval -2.4 to 0.8	-0.2 Units on a Scale Interval -0.9 to 0.5
Change From Baseline on the NSAA Score - Overall Baseline Week 17	0.3 Units on a Scale Interval -1.1 to 1.6	-2.2 Units on a Scale Interval -5.8 to 1.5	-0.9 Units on a Scale Interval -2.7 to 0.9	-0.9 Units on a Scale Interval -2.3 to 0.4
Change From Baseline on the NSAA Score - Overall Baseline Week 25	0.1 Units on a Scale Interval -1.5 to 1.7	-1.4 Units on a Scale Interval -3.1 to 0.3	-2.2 Units on a Scale Interval -4.7 to 0.4	-1.2 Units on a Scale Interval -2.3 to 0.0
Change From Baseline on the NSAA Score - Overall Baseline Week 33	-0.4 Units on a Scale Interval -2.0 to 1.2	-1.5 Units on a Scale Interval -3.1 to 0.1	-2.9 Units on a Scale Interval -5.1 to -0.7	-1.6 Units on a Scale Interval -2.7 to -0.6
Change From Baseline on the NSAA Score - Overall Baseline Week 41	-1.5 Units on a Scale Interval -3.8 to 0.7	-2.7 Units on a Scale Interval -4.5 to -0.8	-3.6 Units on a Scale Interval -6.0 to -1.2	-2.6 Units on a Scale Interval -3.8 to -1.4
Change From Baseline on the NSAA Score - Overall Baseline Week 49	-1.8 Units on a Scale Interval -4.2 to 0.6	-3.4 Units on a Scale Interval -5.5 to -1.2	-4.2 Units on a Scale Interval -6.9 to -1.6	-3.1 Units on a Scale Interval -4.5 to -1.8
Change From Baseline on the NSAA Score - Overall Baseline Week 57	-2.6 Units on a Scale Interval -5.1 to -0.2	-3.7 Units on a Scale Interval -6.0 to -1.3	-5.5 Units on a Scale Interval -9.3 to -1.6	-3.9 Units on a Scale Interval -5.6 to -2.3
Change From Baseline on the NSAA Score - Overall Baseline Week 65	-2.7 Units on a Scale Interval -5.4 to -0.1	-3.8 Units on a Scale Interval -6.1 to -1.5	-5.8 Units on a Scale Interval -9.6 to -1.9	-4.1 Units on a Scale Interval -5.8 to -2.5
Change From Baseline on the NSAA Score - Overall Baseline Week 73	-4.7 Units on a Scale Interval -7.7 to -1.6	-5.1 Units on a Scale Interval -7.4 to -2.7	-5.8 Units on a Scale Interval -8.8 to -2.7	-5.2 Units on a Scale Interval -6.7 to -3.6
Change From Baseline on the NSAA Score - Overall Baseline Week 81	-4.1 Units on a Scale Interval -6.8 to -1.3	-4.5 Units on a Scale Interval -6.9 to -2.1	-6.0 Units on a Scale Interval -9.3 to -2.6	-4.9 Units on a Scale Interval -6.4 to -3.3
Change From Baseline on the NSAA Score - Overall Baseline Week 89	-4.2 Units on a Scale Interval -7.5 to -1.0	-6.2 Units on a Scale Interval -8.5 to -3.9	-7.4 Units on a Scale Interval -10.4 to -4.3	-6.0 Units on a Scale Interval -7.6 to -4.4
Change From Baseline on the NSAA Score - Overall Baseline Week 97	-4.4 Units on a Scale Interval -7.7 to -1.1	-6.7 Units on a Scale Interval -9.3 to -4.0	-7.0 Units on a Scale Interval -10.0 to -3.9	-6.1 Units on a Scale Interval -7.7 to -4.4
Change From Baseline on the NSAA Score - Overall Baseline Week 110	-5.1 Units on a Scale Interval -8.4 to -1.8	-7.2 Units on a Scale Interval -9.8 to -4.7	-5.9 Units on a Scale Interval -8.9 to -2.9	-6.1 Units on a Scale Interval -7.7 to -4.5
Change From Baseline on the NSAA Score - Overall Baseline Week 122	-6.4 Units on a Scale Interval -11.7 to -1.0	-7.2 Units on a Scale Interval -10.7 to -3.6	-7.6 Units on a Scale Interval -12.0 to -3.3	-7.1 Units on a Scale Interval -9.4 to -4.8
Change From Baseline on the NSAA Score - Overall Baseline Week 170	-11.5 Units on a Scale Insufficient number of participants to calculate a 95% Confidence Interval.	-12.0 Units on a Scale Insufficient number of participants to calculate a 95% Confidence Interval.	-7.0 Units on a Scale Insufficient number of participants to calculate a 95% Confidence Interval.	-10.2 Units on a Scale Interval -15.6 to -4.8

SECONDARY outcome

Timeframe: Baseline, Weeks 13, 25, 49, 73.

Rise from supine was a timed functional test within NSAA. This test of time-to-stand from supine was analyzed separately for summary tabulation along with the total NSAA score. Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. Week 1 was counted starting from the study treatment in study B5161004.

Outcome measures

Outcome measures
Measure	Sequence 1 n=19 Participants In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 2 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 3 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Total n=59 Participants Sum of all participants in the study B5161004
Change From Baseline on the NSAA - Time to Stand From Supine - B5161004 Baseline Baseline	4.517 Seconds Interval 2.612 to 6.421	6.508 Seconds Interval 3.996 to 9.02	6.250 Seconds Interval 4.552 to 7.948	5.948 Seconds Interval 4.751 to 7.144
Change From Baseline on the NSAA - Time to Stand From Supine - B5161004 Baseline Week 13	0.330 Seconds Interval -0.231 to 0.891	1.353 Seconds Interval 0.357 to 2.349	-0.038 Seconds Interval -0.931 to 0.856	0.662 Seconds Interval 0.121 to 1.203
Change From Baseline on the NSAA - Time to Stand From Supine - B5161004 Baseline Week 25	-0.113 Seconds Interval -0.585 to 0.36	1.463 Seconds Interval 0.315 to 2.61	-0.167 Seconds Interval -1.41 to 1.076	0.569 Seconds Interval -0.112 to 1.251
Change From Baseline on the NSAA - Time to Stand From Supine - B5161004 Baseline Week 49	0.670 Seconds 95% Confidence Interval was not applicable for individual value.	1.518 Seconds Interval -1.384 to 4.419	2.978 Seconds Interval -1.944 to 7.899	2.072 Seconds Interval 0.246 to 3.898
Change From Baseline on the NSAA - Time to Stand From Supine - B5161004 Baseline Week 73	—	10.170 Seconds Insufficient number of participants to calculate a 95% Confidence Interval.	2.300 Seconds Insufficient number of participants to calculate a 95% Confidence Interval.	6.235 Seconds Insufficient number of participants to calculate a 95% Confidence Interval.

SECONDARY outcome

Timeframe: Baseline, Weeks 9,17,25,33,41,49,57,65,73,81,89,97,110,122,146,170.

Rise from supine was a timed functional test within NSAA. This test of time-to-stand from supine was analyzed separately for summary tabulation along with the total NSAA score. This is the overall change from baseline which included the change since enrolling in the parent study B5161002. Overall baseline was defined as the last pre-dose assessment prior to the first day of dosing in study B5161002. Week 1 was counted starting from the study treatment in study B5161002.

Outcome measures

Outcome measures
Measure	Sequence 1 n=19 Participants In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 2 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 3 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Total n=59 Participants Sum of all participants in the study B5161004
Change From Baseline on the NSAA - Time to Stand From Supine - Overall Baseline Baseline	6.440 Seconds Interval 4.446 to 8.434	7.059 Seconds Interval 2.997 to 11.122	7.046 Seconds Interval 5.13 to 8.962	6.840 Seconds Interval 5.348 to 8.331
Change From Baseline on the NSAA - Time to Stand From Supine - Overall Baseline Week 9	-0.140 Seconds Interval -1.049 to 0.769	0.486 Seconds Interval -0.19 to 1.163	0.867 Seconds Interval -0.101 to 1.834	0.356 Seconds Interval -0.116 to 0.829
Change From Baseline on the NSAA - Time to Stand From Supine - Overall Baseline Week 17	10.251 Seconds Interval -11.639 to 32.142	1.123 Seconds Interval 0.185 to 2.06	1.148 Seconds Interval 0.013 to 2.282	4.693 Seconds Interval -3.384 to 12.77
Change From Baseline on the NSAA - Time to Stand From Supine - Overall Baseline Week 25	1.283 Seconds Interval -0.135 to 2.701	0.514 Seconds Interval 0.055 to 0.973	1.456 Seconds Interval -0.401 to 3.313	1.086 Seconds Interval 0.364 to 1.808
Change From Baseline on the NSAA - Time to Stand From Supine - Overall Baseline Week 33	1.382 Seconds Interval -0.038 to 2.802	0.392 Seconds Interval -0.412 to 1.195	1.143 Seconds Interval -1.2 to 3.485	1.000 Seconds Interval 0.166 to 1.834
Change From Baseline on the NSAA - Time to Stand From Supine - Overall Baseline Week 41	1.184 Seconds Interval 0.123 to 2.246	0.526 Seconds Interval -0.23 to 1.282	1.620 Seconds Interval -0.213 to 3.453	1.086 Seconds Interval 0.445 to 1.726
Change From Baseline on the NSAA - Time to Stand From Supine - Overall Baseline Week 49	1.642 Seconds Interval -0.005 to 3.289	0.730 Seconds Interval -0.466 to 1.926	1.630 Seconds Interval 0.269 to 2.991	1.350 Seconds Interval 0.582 to 2.118
Change From Baseline on the NSAA - Time to Stand From Supine - Overall Baseline Week 57	1.577 Seconds Interval -0.212 to 3.366	1.376 Seconds Interval -0.184 to 2.937	1.316 Seconds Interval -0.581 to 3.212	1.439 Seconds Interval 0.534 to 2.343
Change From Baseline on the NSAA - Time to Stand From Supine - Overall Baseline Week 65	1.590 Seconds Interval -0.715 to 3.895	1.570 Seconds Interval -0.113 to 3.253	1.907 Seconds Interval -0.652 to 4.465	1.672 Seconds Interval 0.556 to 2.788
Change From Baseline on the NSAA - Time to Stand From Supine - Overall Baseline Week 73	2.664 Seconds Interval 0.149 to 5.18	1.765 Seconds Interval 0.012 to 3.517	2.266 Seconds Interval 0.41 to 4.123	2.244 Seconds Interval 1.155 to 3.333
Change From Baseline on the NSAA - Time to Stand From Supine - Overall Baseline Week 81	2.153 Seconds Interval -0.046 to 4.352	2.422 Seconds Interval -0.327 to 5.17	1.971 Seconds Interval -0.291 to 4.233	2.190 Seconds Interval 0.948 to 3.431
Change From Baseline on the NSAA - Time to Stand From Supine - Overall Baseline Week 89	2.538 Seconds Interval 0.479 to 4.598	3.249 Seconds Interval -1.598 to 8.096	2.824 Seconds Interval 0.109 to 5.539	2.860 Seconds Interval 1.166 to 4.553
Change From Baseline on the NSAA - Time to Stand From Supine - Overall Baseline Week 97	1.009 Seconds Interval -0.44 to 2.458	2.418 Seconds Interval 0.299 to 4.537	1.933 Seconds Interval 0.279 to 3.587	1.860 Seconds Interval 0.896 to 2.823
Change From Baseline on the NSAA - Time to Stand From Supine - Overall Baseline Week 110	0.792 Seconds Interval -0.611 to 2.194	3.753 Seconds Interval 1.266 to 6.239	2.884 Seconds Interval -0.807 to 6.576	2.769 Seconds Interval 1.226 to 4.311
Change From Baseline on the NSAA - Time to Stand From Supine - Overall Baseline Week 122	-0.133 Seconds Interval -2.124 to 1.859	4.543 Seconds Interval 1.277 to 7.808	1.750 Seconds Interval -0.12 to 3.62	2.573 Seconds Interval 0.903 to 4.243
Change From Baseline on the NSAA - Time to Stand From Supine - Overall Baseline Week 146	-0.400 Seconds 95% Confidence Interval was not applicable for individual value.	5.295 Seconds Interval -5.207 to 15.797	4.978 Seconds Interval -1.086 to 11.041	4.521 Seconds Interval 0.662 to 8.381
Change From Baseline on the NSAA - Time to Stand From Supine - Overall Baseline Week 170	—	13.780 Seconds Insufficient number of participants to calculate a 95% Confidence Interval.	4.300 Seconds Insufficient number of participants to calculate a 95% Confidence Interval.	9.040 Seconds Insufficient number of participants to calculate a 95% Confidence Interval.

SECONDARY outcome

Timeframe: Baseline, Weeks 13, 25, 49, 73.

A time to event analysis was performed for loss of ambulation. Loss of ambulation was defined as the inability to walk unassisted and without braces for at least 10 m, as assessed and reported by the investigator at each study visit, and confirmed by the inability to walk/run 10 m (as 1 component of the NSAA) evaluated at the next visit at which timed function tests were performed. Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. Week 1 was counted starting from the study treatment in study B5161004.

Outcome measures

Outcome measures
Measure	Sequence 1 n=19 Participants In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 2 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 3 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Total n=59 Participants Sum of all participants in the study B5161004
Change From Baseline on the NSAA - Time to Complete 10 m Run/Walk - B5161004 Baseline Week 49	0.665 Seconds Interval -0.546 to 1.864	-0.735 Seconds Interval -4.419 to 2.949	0.488 Seconds Interval -0.822 to 1.797	0.139 Seconds Interval -0.809 to 1.087
Change From Baseline on the NSAA - Time to Complete 10 m Run/Walk - B5161004 Baseline Baseline	6.245 Seconds Interval 4.91 to 7.579	5.894 Seconds Interval 4.694 to 7.094	5.800 Seconds Interval 4.789 to 6.811	5.988 Seconds Interval 5.361 to 6.615
Change From Baseline on the NSAA - Time to Complete 10 m Run/Walk - B5161004 Baseline Week 13	-0.029 Seconds Interval -0.31 to 0.252	0.383 Seconds Interval -1.262 to 2.027	0.089 Seconds Interval -0.195 to 0.372	0.158 Seconds Interval -0.412 to 0.729
Change From Baseline on the NSAA - Time to Complete 10 m Run/Walk - B5161004 Baseline Week 25	0.546 Seconds Interval -0.235 to 1.328	-0.172 Seconds Interval -1.41 to 1.066	0.743 Seconds Interval -0.231 to 1.717	0.334 Seconds Interval -0.204 to 0.872
Change From Baseline on the NSAA - Time to Complete 10 m Run/Walk - B5161004 Baseline Week 73	1.160 Seconds Insufficient number of participants to calculate a 95% Confidence Interval.	0.480 Seconds Insufficient number of participants to calculate a 95% Confidence Interval.	0.600 Seconds Insufficient number of participants to calculate a 95% Confidence Interval.	0.680 Seconds Interval -0.389 to 1.749

SECONDARY outcome

Timeframe: Baseline, Weeks 9,17,25,33,41,49,57,65,73,81,89,97,110,122,146,170.

A time to event analysis was performed for loss of ambulation. Loss of ambulation was defined as the inability to walk unassisted and without braces for at least 10 m, as assessed and reported by the investigator at each study visit, and confirmed by the inability to walk/run 10 m (as 1 component of the NSAA) evaluated at the next visit at which timed function tests were performed. This is the overall change from baseline which included the change since enrolling in the parent study B5161002. Overall baseline was defined as the last pre-dose assessment prior to the first day of dosing in study B5161002. Week 1 was counted starting from the study treatment in study B5161002.

Outcome measures

Outcome measures
Measure	Sequence 1 n=19 Participants In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 2 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 3 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Total n=59 Participants Sum of all participants in the study B5161004
Change From Baseline on the NSAA - Time to Complete 10 m Run/Walk - Overall Baseline Week 110	1.085 Seconds Interval 0.048 to 2.122	1.238 Seconds Interval 0.382 to 2.095	0.300 Seconds Interval -0.8 to 1.4	0.936 Seconds Interval 0.41 to 1.462
Change From Baseline on the NSAA - Time to Complete 10 m Run/Walk - Overall Baseline Week 170	3.300 Seconds Insufficient number of participants to calculate a 95% Confidence Interval.	2.090 Seconds Insufficient number of participants to calculate a 95% Confidence Interval.	1.800 Seconds Insufficient number of participants to calculate a 95% Confidence Interval.	2.320 Seconds Interval -1.11 to 5.75
Change From Baseline on the NSAA - Time to Complete 10 m Run/Walk - Overall Baseline Baseline	5.780 Seconds Interval 5.031 to 6.529	5.862 Seconds Interval 5.073 to 6.652	6.609 Seconds Interval 5.596 to 7.623	6.078 Seconds Interval 5.606 to 6.55
Change From Baseline on the NSAA - Time to Complete 10 m Run/Walk - Overall Baseline Week 9	0.159 Seconds Interval -0.111 to 0.43	0.008 Seconds Interval -0.235 to 0.251	0.114 Seconds Interval -0.46 to 0.689	0.096 Seconds Interval -0.106 to 0.298
Change From Baseline on the NSAA - Time to Complete 10 m Run/Walk - Overall Baseline Week 17	0.173 Seconds Interval -0.154 to 0.5	0.115 Seconds Interval -0.268 to 0.497	0.083 Seconds Interval -0.61 to 0.776	0.126 Seconds Interval -0.131 to 0.382
Change From Baseline on the NSAA - Time to Complete 10 m Run/Walk - Overall Baseline Week 25	0.468 Seconds Interval 0.182 to 0.754	0.719 Seconds Interval -0.192 to 1.631	0.110 Seconds Interval -0.48 to 0.7	0.446 Seconds Interval 0.101 to 0.792
Change From Baseline on the NSAA - Time to Complete 10 m Run/Walk - Overall Baseline Week 33	0.348 Seconds Interval -0.109 to 0.805	0.417 Seconds Interval -0.241 to 1.076	0.264 Seconds Interval -0.319 to 0.846	0.348 Seconds Interval 0.044 to 0.651
Change From Baseline on the NSAA - Time to Complete 10 m Run/Walk - Overall Baseline Week 41	0.445 Seconds Interval -0.04 to 0.93	0.471 Seconds Interval -0.314 to 1.256	0.845 Seconds Interval -0.091 to 1.782	0.567 Seconds Interval 0.179 to 0.956
Change From Baseline on the NSAA - Time to Complete 10 m Run/Walk - Overall Baseline Week 49	0.360 Seconds Interval -0.117 to 0.837	0.869 Seconds Interval -0.326 to 2.065	0.145 Seconds Interval -0.655 to 0.945	0.482 Seconds Interval -0.007 to 0.97
Change From Baseline on the NSAA - Time to Complete 10 m Run/Walk - Overall Baseline Week 57	1.018 Seconds Interval 0.383 to 1.653	1.573 Seconds Interval -0.263 to 3.408	0.539 Seconds Interval -0.214 to 1.292	1.102 Seconds Interval 0.399 to 1.804
Change From Baseline on the NSAA - Time to Complete 10 m Run/Walk - Overall Baseline Week 81	1.243 Seconds Interval 0.311 to 2.174	0.625 Seconds Interval -0.033 to 1.283	0.687 Seconds Interval -0.406 to 1.779	0.882 Seconds Interval 0.391 to 1.372
Change From Baseline on the NSAA - Time to Complete 10 m Run/Walk - Overall Baseline Week 65	1.482 Seconds Interval 0.572 to 2.391	0.988 Seconds Interval 0.19 to 1.786	0.745 Seconds Interval -0.069 to 1.559	1.121 Seconds Interval 0.649 to 1.592
Change From Baseline on the NSAA - Time to Complete 10 m Run/Walk - Overall Baseline Week 73	1.156 Seconds Interval 0.242 to 2.071	1.128 Seconds Interval -0.014 to 2.27	0.324 Seconds Interval -0.494 to 1.142	0.933 Seconds Interval 0.391 to 1.476
Change From Baseline on the NSAA - Time to Complete 10 m Run/Walk - Overall Baseline Week 89	1.287 Seconds Interval 0.332 to 2.242	0.837 Seconds Interval 0.102 to 1.572	0.460 Seconds Interval -0.469 to 1.389	0.897 Seconds Interval 0.415 to 1.379
Change From Baseline on the NSAA - Time to Complete 10 m Run/Walk - Overall Baseline Week 97	0.928 Seconds Interval 0.193 to 1.663	0.883 Seconds Interval -0.405 to 2.172	0.670 Seconds Interval -0.393 to 1.733	0.837 Seconds Interval 0.304 to 1.369
Change From Baseline on the NSAA - Time to Complete 10 m Run/Walk - Overall Baseline Week 122	1.195 Seconds Interval -0.064 to 2.454	1.416 Seconds Interval 0.65 to 2.182	0.914 Seconds Interval -0.008 to 1.837	1.205 Seconds Interval 0.719 to 1.69
Change From Baseline on the NSAA - Time to Complete 10 m Run/Walk - Overall Baseline Week 146	2.138 Seconds Interval -0.866 to 5.141	1.588 Seconds Interval -1.542 to 4.717	1.662 Seconds Interval 0.096 to 3.228	1.785 Seconds Interval 0.84 to 2.731

SECONDARY outcome

Timeframe: Baseline, Weeks 13, 25, 49 and 73.

ROM of the ankle was evaluated by goniometry and any occurrences of ankle contractures were recorded. In order to provide optimal testing conditions and consistency in endpoint measurements, the functional assessment of ankle ROM was completed at approximately the same time of day. Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. Week 1 was counted starting from the study treatment in study B5161004.

Outcome measures

Outcome measures
Measure	Sequence 1 n=19 Participants In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 2 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 3 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Total n=59 Participants Sum of all participants in the study B5161004
Change From Baseline on the Ankle Range of Motion (ROM) - B5161004 Baseline Left Ankle - Baseline	0.6 Degrees of Passive Flexion Interval -3.7 to 4.8	-0.4 Degrees of Passive Flexion Interval -6.8 to 5.9	-7.8 Degrees of Passive Flexion Interval -13.8 to -1.9	-2.8 Degrees of Passive Flexion Interval -6.0 to 0.4
Change From Baseline on the Ankle Range of Motion (ROM) - B5161004 Baseline Left Ankle - Week 13	-2.1 Degrees of Passive Flexion Interval -5.2 to 1.0	-1.0 Degrees of Passive Flexion Interval -5.2 to 3.2	-0.9 Degrees of Passive Flexion Interval -3.7 to 1.8	-1.3 Degrees of Passive Flexion Interval -3.2 to 0.5
Change From Baseline on the Ankle Range of Motion (ROM) - B5161004 Baseline Left Ankle - Week 49	-1.7 Degrees of Passive Flexion Interval -12.0 to 8.6	-6.2 Degrees of Passive Flexion Interval -15.2 to 2.9	-4.0 Degrees of Passive Flexion Interval -11.4 to 3.4	-3.9 Degrees of Passive Flexion Interval -8.1 to 0.4
Change From Baseline on the Ankle Range of Motion (ROM) - B5161004 Baseline Right Ankle - Week 13	-0.8 Degrees of Passive Flexion Interval -4.5 to 3.0	0.4 Degrees of Passive Flexion Interval -3.0 to 3.9	0.8 Degrees of Passive Flexion Interval -2.1 to 3.7	0.2 Degrees of Passive Flexion Interval -1.6 to 2.0
Change From Baseline on the Ankle Range of Motion (ROM) - B5161004 Baseline Right Ankle - Week 25	-1.5 Degrees of Passive Flexion Interval -5.3 to 2.2	-1.7 Degrees of Passive Flexion Interval -7.0 to 3.6	-2.1 Degrees of Passive Flexion Interval -6.0 to 1.8	-1.8 Degrees of Passive Flexion Interval -4.1 to 0.5
Change From Baseline on the Ankle Range of Motion (ROM) - B5161004 Baseline Right Ankle - Week 73	-1.0 Degrees of Passive Flexion Insufficient number of participants to calculate a 95% Confidence Interval.	3.0 Degrees of Passive Flexion Insufficient number of participants to calculate a 95% Confidence Interval.	5.5 Degrees of Passive Flexion Insufficient number of participants to calculate a 95% Confidence Interval.	2.5 Degrees of Passive Flexion Interval -7.1 to 12.1
Change From Baseline on the Ankle Range of Motion (ROM) - B5161004 Baseline Right Ankle - Week 49	-4.1 Degrees of Passive Flexion Interval -12.3 to 4.0	-3.3 Degrees of Passive Flexion Interval -6.1 to -0.5	-3.0 Degrees of Passive Flexion Interval -6.1 to 0.1	-3.5 Degrees of Passive Flexion Interval -6.1 to -0.9
Change From Baseline on the Ankle Range of Motion (ROM) - B5161004 Baseline Left Ankle - Week 25	-2.2 Degrees of Passive Flexion Interval -5.4 to 1.0	-1.8 Degrees of Passive Flexion Interval -8.7 to 5.0	-2.4 Degrees of Passive Flexion Interval -6.4 to 1.5	-2.2 Degrees of Passive Flexion Interval -4.7 to 0.4
Change From Baseline on the Ankle Range of Motion (ROM) - B5161004 Baseline Left Ankle - Week 73	-2.5 Degrees of Passive Flexion Insufficient number of participants to calculate a 95% Confidence Interval.	-3.0 Degrees of Passive Flexion Insufficient number of participants to calculate a 95% Confidence Interval.	0.5 Degrees of Passive Flexion Insufficient number of participants to calculate a 95% Confidence Interval.	-1.7 Degrees of Passive Flexion Interval -6.8 to 3.4
Change From Baseline on the Ankle Range of Motion (ROM) - B5161004 Baseline Right Ankle - Baseline	0.0 Degrees of Passive Flexion Interval -4.2 to 4.2	-3.1 Degrees of Passive Flexion Interval -10.3 to 4.2	-10.3 Degrees of Passive Flexion Interval -17.9 to -2.7	-4.7 Degrees of Passive Flexion Interval -8.5 to -0.9

SECONDARY outcome

Timeframe: Baseline, Weeks 9,17,25,33,41,49,57,65,73,81,89,97,110,122,146,170.

ROM of the ankle was evaluated by goniometry and any occurrences of ankle contractures were recorded. In order to provide optimal testing conditions and consistency in endpoint measurements, the functional assessment of ankle ROM was completed at approximately the same time of day. This is the overall change from baseline which included the change since enrolling in the parent study B5161002. Overall baseline was defined as the last pre-dose assessment prior to the first day of dosing in study B5161002. Week 1 was counted starting from the study treatment in study B5161002.

Outcome measures

Outcome measures
Measure	Sequence 1 n=19 Participants In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 2 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 3 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Total n=59 Participants Sum of all participants in the study B5161004
Change From Baseline on the Ankle ROM - Overall Baseline Left Ankle - Baseline	7.1 Degrees of Passive Flexion Interval 4.7 to 9.5	2.6 Degrees of Passive Flexion Interval -1.8 to 6.9	1.6 Degrees of Passive Flexion Interval -1.3 to 4.4	3.7 Degrees of Passive Flexion Interval 1.8 to 5.6
Change From Baseline on the Ankle ROM - Overall Baseline Left Ankle - Week 9	-1.8 Degrees of Passive Flexion Interval -4.1 to 0.4	-0.8 Degrees of Passive Flexion Interval -3.6 to 2.1	-0.2 Degrees of Passive Flexion Interval -2.7 to 2.3	-0.9 Degrees of Passive Flexion Interval -2.3 to 0.5
Change From Baseline on the Ankle ROM - Overall Baseline Left Ankle - Week 146	-10.0 Degrees of Passive Flexion Interval -21.7 to 1.7	-10.8 Degrees of Passive Flexion Interval -19.7 to -1.9	-10.9 Degrees of Passive Flexion Interval -22.9 to 1.2	-10.6 Degrees of Passive Flexion Interval -15.7 to -5.4
Change From Baseline on the Ankle ROM - Overall Baseline Right Ankle - Week 73	-3.6 Degrees of Passive Flexion Interval -8.0 to 0.8	-3.0 Degrees of Passive Flexion Interval -10.1 to 4.2	-8.0 Degrees of Passive Flexion Interval -12.6 to -3.4	-4.9 Degrees of Passive Flexion Interval -7.9 to -1.8
Change From Baseline on the Ankle ROM - Overall Baseline Left Ankle - Week 17	-2.5 Degrees of Passive Flexion Interval -5.5 to 0.4	-2.0 Degrees of Passive Flexion Interval -4.4 to 0.4	-1.0 Degrees of Passive Flexion Interval -3.4 to 1.4	-1.8 Degrees of Passive Flexion Interval -3.2 to -0.4
Change From Baseline on the Ankle ROM - Overall Baseline Left Ankle - Week 25	-2.3 Degrees of Passive Flexion Interval -5.5 to 1.0	-4.7 Degrees of Passive Flexion Interval -7.6 to -1.8	0.0 Degrees of Passive Flexion Interval -2.0 to 2.0	-2.4 Degrees of Passive Flexion Interval -3.9 to -0.8
Change From Baseline on the Ankle ROM - Overall Baseline Left Ankle - Week 33	-1.1 Degrees of Passive Flexion Interval -4.9 to 2.7	-2.4 Degrees of Passive Flexion Interval -5.1 to 0.3	-1.9 Degrees of Passive Flexion Interval -3.8 to 0.0	-1.8 Degrees of Passive Flexion Interval -3.4 to -0.2
Change From Baseline on the Ankle ROM - Overall Baseline Left Ankle - Week 41	-2.4 Degrees of Passive Flexion Interval -6.0 to 1.2	-3.8 Degrees of Passive Flexion Interval -6.3 to -1.2	-2.1 Degrees of Passive Flexion Interval -4.6 to 0.4	-2.8 Degrees of Passive Flexion Interval -4.3 to -1.2
Change From Baseline on the Ankle ROM - Overall Baseline Left Ankle - Week 49	-3.2 Degrees of Passive Flexion Interval -6.6 to 0.2	-5.5 Degrees of Passive Flexion Interval -8.9 to -2.1	-2.3 Degrees of Passive Flexion Interval -5.4 to 0.9	-3.7 Degrees of Passive Flexion Interval -5.5 to -1.8
Change From Baseline on the Ankle ROM - Overall Baseline Left Ankle - Week 57	-3.5 Degrees of Passive Flexion Interval -6.5 to -0.6	-6.1 Degrees of Passive Flexion Interval -10.4 to -1.7	-5.8 Degrees of Passive Flexion Interval -10.0 to -1.6	-5.1 Degrees of Passive Flexion Interval -7.3 to -3.0
Change From Baseline on the Ankle ROM - Overall Baseline Left Ankle - Week 65	-4.1 Degrees of Passive Flexion Interval -7.8 to -0.3	-5.4 Degrees of Passive Flexion Interval -12.6 to 1.9	-5.2 Degrees of Passive Flexion Interval -9.3 to -1.1	-4.9 Degrees of Passive Flexion Interval -7.8 to -2.0
Change From Baseline on the Ankle ROM - Overall Baseline Left Ankle - Week 73	-2.5 Degrees of Passive Flexion Interval -6.6 to 1.6	-4.6 Degrees of Passive Flexion Interval -12.2 to 3.1	-6.6 Degrees of Passive Flexion Interval -10.4 to -2.7	-4.6 Degrees of Passive Flexion Interval -7.6 to -1.5
Change From Baseline on the Ankle ROM - Overall Baseline Left Ankle - Week 81	-6.1 Degrees of Passive Flexion Interval -10.7 to -1.5	-2.7 Degrees of Passive Flexion Interval -9.6 to 4.3	-8.7 Degrees of Passive Flexion Interval -13.2 to -4.1	-5.9 Degrees of Passive Flexion Interval -8.9 to -2.9
Change From Baseline on the Ankle ROM - Overall Baseline Left Ankle - Week 89	-9.9 Degrees of Passive Flexion Interval -16.2 to -3.7	-6.3 Degrees of Passive Flexion Interval -16.0 to 3.4	-8.4 Degrees of Passive Flexion Interval -13.6 to -3.1	-8.1 Degrees of Passive Flexion Interval -12.2 to -4.1
Change From Baseline on the Ankle ROM - Overall Baseline Left Ankle - Week 97	-7.9 Degrees of Passive Flexion Interval -14.1 to -1.8	-10.0 Degrees of Passive Flexion Interval -16.7 to -3.2	-9.3 Degrees of Passive Flexion Interval -13.7 to -4.8	-9.1 Degrees of Passive Flexion Interval -12.2 to -5.9
Change From Baseline on the Ankle ROM - Overall Baseline Left Ankle - Week 110	-8.3 Degrees of Passive Flexion Interval -14.2 to -2.4	-5.9 Degrees of Passive Flexion Interval -12.8 to 1.0	-9.9 Degrees of Passive Flexion Interval -15.4 to -4.4	-8.1 Degrees of Passive Flexion Interval -11.4 to -4.8
Change From Baseline on the Ankle ROM - Overall Baseline Left Ankle - Week 122	-8.7 Degrees of Passive Flexion Interval -16.4 to -1.1	-5.7 Degrees of Passive Flexion Interval -12.8 to 1.5	-11.5 Degrees of Passive Flexion Interval -19.0 to -4.0	-8.8 Degrees of Passive Flexion Interval -12.7 to -4.8
Change From Baseline on the Ankle ROM - Overall Baseline Left Ankle - Week 170	-6.5 Degrees of Passive Flexion Insufficient number of participants to calculate a 95% Confidence Interval.	-6.0 Degrees of Passive Flexion Insufficient number of participants to calculate a 95% Confidence Interval.	-9.0 Degrees of Passive Flexion Insufficient number of participants to calculate a 95% Confidence Interval.	-7.2 Degrees of Passive Flexion Interval -13.4 to -1.0
Change From Baseline on the Ankle ROM - Overall Baseline Right Ankle - Baseline	6.7 Degrees of Passive Flexion Interval 4.4 to 9.1	1.0 Degrees of Passive Flexion Interval -4.0 to 6.0	1.5 Degrees of Passive Flexion Interval -1.6 to 4.6	3.0 Degrees of Passive Flexion Interval 0.9 to 5.1
Change From Baseline on the Ankle ROM - Overall Baseline Right Ankle - Week 9	-1.9 Degrees of Passive Flexion Interval -5.0 to 1.2	-0.8 Degrees of Passive Flexion Interval -3.5 to 1.9	-1.3 Degrees of Passive Flexion Interval -3.6 to 1.0	-1.3 Degrees of Passive Flexion Interval -2.8 to 0.2
Change From Baseline on the Ankle ROM - Overall Baseline Right Ankle - Week 17	-2.2 Degrees of Passive Flexion Interval -6.3 to 2.0	-1.8 Degrees of Passive Flexion Interval -3.9 to 0.3	-2.0 Degrees of Passive Flexion Interval -4.8 to 0.9	-2.0 Degrees of Passive Flexion Interval -3.7 to -0.3
Change From Baseline on the Ankle ROM - Overall Baseline Right Ankle - Week 25	-1.5 Degrees of Passive Flexion Interval -5.2 to 2.1	-4.5 Degrees of Passive Flexion Interval -7.6 to -1.3	-3.1 Degrees of Passive Flexion Interval -5.8 to -0.4	-3.1 Degrees of Passive Flexion Interval -4.8 to -1.3
Change From Baseline on the Ankle ROM - Overall Baseline Right Ankle - Week 33	0.4 Degrees of Passive Flexion Interval -3.7 to 4.5	-1.6 Degrees of Passive Flexion Interval -4.7 to 1.6	-3.4 Degrees of Passive Flexion Interval -5.9 to -0.8	-1.5 Degrees of Passive Flexion Interval -3.3 to 0.3
Change From Baseline on the Ankle ROM - Overall Baseline Right Ankle - Week 41	-2.7 Degrees of Passive Flexion Interval -6.0 to 0.6	-3.1 Degrees of Passive Flexion Interval -6.0 to -0.1	-2.7 Degrees of Passive Flexion Interval -5.7 to 0.4	-2.8 Degrees of Passive Flexion Interval -4.5 to -1.1
Change From Baseline on the Ankle ROM - Overall Baseline Right Ankle - Week 49	-3.8 Degrees of Passive Flexion Interval -7.6 to -0.1	-4.5 Degrees of Passive Flexion Interval -7.9 to -1.1	-2.5 Degrees of Passive Flexion Interval -6.3 to 1.4	-3.6 Degrees of Passive Flexion Interval -5.6 to -1.6
Change From Baseline on the Ankle ROM - Overall Baseline Right Ankle - Week 57	-2.5 Degrees of Passive Flexion Interval -6.1 to 1.0	-5.3 Degrees of Passive Flexion Interval -9.8 to -0.8	-7.9 Degrees of Passive Flexion Interval -12.4 to -3.5	-5.2 Degrees of Passive Flexion Interval -7.6 to -2.9
Change From Baseline on the Ankle ROM - Overall Baseline Right Ankle - Week 65	-4.7 Degrees of Passive Flexion Interval -9.1 to -0.4	-5.4 Degrees of Passive Flexion Interval -12.6 to 1.9	-6.6 Degrees of Passive Flexion Interval -10.8 to -2.4	-5.6 Degrees of Passive Flexion Interval -8.5 to -2.6
Change From Baseline on the Ankle ROM - Overall Baseline Right Ankle - Week 81	-5.1 Degrees of Passive Flexion Interval -9.7 to -0.5	-1.4 Degrees of Passive Flexion Interval -7.9 to 5.1	-10.0 Degrees of Passive Flexion Interval -14.9 to -5.1	-5.6 Degrees of Passive Flexion Interval -8.7 to -2.6
Change From Baseline on the Ankle ROM - Overall Baseline Right Ankle - Week 89	-9.4 Degrees of Passive Flexion Interval -15.4 to -3.4	-6.8 Degrees of Passive Flexion Interval -15.4 to 1.9	-10.4 Degrees of Passive Flexion Interval -15.8 to -5.0	-8.8 Degrees of Passive Flexion Interval -12.6 to -5.0
Change From Baseline on the Ankle ROM - Overall Baseline Right Ankle - Week 97	-7.5 Degrees of Passive Flexion Interval -12.4 to -2.5	-10.6 Degrees of Passive Flexion Interval -18.3 to -2.9	-11.8 Degrees of Passive Flexion Interval -17.5 to -6.1	-10.0 Degrees of Passive Flexion Interval -13.4 to -6.6
Change From Baseline on the Ankle ROM - Overall Baseline Right Ankle - Week 110	-7.4 Degrees of Passive Flexion Interval -13.9 to -0.9	-5.9 Degrees of Passive Flexion Interval -11.6 to -0.2	-10.4 Degrees of Passive Flexion Interval -16.4 to -4.3	-7.9 Degrees of Passive Flexion Interval -11.2 to -4.6
Change From Baseline on the Ankle ROM - Overall Baseline Right Ankle - Week 122	-7.6 Degrees of Passive Flexion Interval -14.9 to -0.3	-6.8 Degrees of Passive Flexion Interval -14.3 to 0.6	-12.7 Degrees of Passive Flexion Interval -20.1 to -5.3	-9.3 Degrees of Passive Flexion Interval -13.3 to -5.3
Change From Baseline on the Ankle ROM - Overall Baseline Right Ankle - Week 146	-12.6 Degrees of Passive Flexion Interval -24.4 to -0.7	-9.2 Degrees of Passive Flexion Interval -20.6 to 2.2	-12.1 Degrees of Passive Flexion Interval -23.5 to -0.7	-11.4 Degrees of Passive Flexion Interval -16.8 to -6.0
Change From Baseline on the Ankle ROM - Overall Baseline Right Ankle - Week 170	-7.5 Degrees of Passive Flexion Insufficient number of participants to calculate a 95% Confidence Interval.	-3.5 Degrees of Passive Flexion Insufficient number of participants to calculate a 95% Confidence Interval.	-12.0 Degrees of Passive Flexion Insufficient number of participants to calculate a 95% Confidence Interval.	-7.7 Degrees of Passive Flexion Interval -16.3 to 1.0

SECONDARY outcome

Timeframe: Baseline, Weeks 13, 25, 49 and 73.

The PUL scale was used to assess motor performance of the upper limb for individuals with DMD. The PUL scale includes 22 items; an entry item defining the starting functional level, and 21 items subdivided into 3 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 to 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; shoulder maximum 16, middle level maximum score 34 and distal level maximum score 24. In order to provide optimal testing conditions and consistency in endpoint measurements, the functional assessment of PUL was completed at approximately the same time of day. Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. Week 1 was counted starting from the study treatment in study B5161004.

Outcome measures

Outcome measures
Measure	Sequence 1 n=19 Participants In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 2 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 3 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Total n=59 Participants Sum of all participants in the study B5161004
Change From Baseline on the Performance of Upper Limb (PUL) Overall Score - B5161004 Baseline Baseline	65.6 Units on a Scale Interval 63.0 to 68.2	65.3 Units on a Scale Interval 61.4 to 69.1	63.8 Units on a Scale Interval 59.9 to 67.8	64.9 Units on a Scale Interval 62.9 to 66.8
Change From Baseline on the Performance of Upper Limb (PUL) Overall Score - B5161004 Baseline Week 13	-1.2 Units on a Scale Interval -2.3 to -0.1	-1.5 Units on a Scale Interval -2.6 to -0.4	-1.8 Units on a Scale Interval -3.7 to 0.0	-1.5 Units on a Scale Interval -2.3 to -0.8
Change From Baseline on the Performance of Upper Limb (PUL) Overall Score - B5161004 Baseline Week 25	-1.2 Units on a Scale Interval -2.3 to -0.2	-3.0 Units on a Scale Interval -5.3 to -0.7	-0.3 Units on a Scale Interval -1.2 to 0.6	-1.5 Units on a Scale Interval -2.4 to -0.6
Change From Baseline on the Performance of Upper Limb (PUL) Overall Score - B5161004 Baseline Week 49	-1.6 Units on a Scale Interval -5.5 to 2.4	-7.8 Units on a Scale Interval -14.1 to -1.6	-2.6 Units on a Scale Interval -6.3 to 1.1	-3.8 Units on a Scale Interval -6.3 to -1.3
Change From Baseline on the Performance of Upper Limb (PUL) Overall Score - B5161004 Baseline Week 73	-13.5 Units on a Scale Insufficient number of participants to calculate a 95% Confidence Interval.	-7.5 Units on a Scale Insufficient number of participants to calculate a 95% Confidence Interval.	-6.0 Units on a Scale Insufficient number of participants to calculate a 95% Confidence Interval.	-9.0 Units on a Scale Interval -15.0 to -3.0

SECONDARY outcome

Timeframe: Baseline, Weeks 9,17,25,33,41,49,57,65,73,81,89,97,110,122,146,170.

The PUL scale was used to assess motor performance of the upper limb for individuals with DMD. The PUL scale includes 22 items; an entry item defining the starting functional level, and 21 items subdivided into 3 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 to 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; shoulder maximum 16, middle level maximum score 34 and distal level maximum score 24. This is the overall change from baseline which included the change since enrolling in parent study B5161002. Overall baseline was defined as the last pre-dose assessment prior to the first day of dosing in study B5161002. Week 1 was counted starting from the study treatment in study B5161002.

Outcome measures

Outcome measures
Measure	Sequence 1 n=19 Participants In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 2 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 3 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Total n=59 Participants Sum of all participants in the study B5161004
Change From Baseline on the PUL Overall Score - Overall Baseline Week 122	-1.4 Units on a Scale Interval -5.3 to 2.5	-2.8 Units on a Scale Interval -6.8 to 1.3	-2.4 Units on a Scale Interval -5.4 to 0.6	-2.2 Units on a Scale Interval -4.1 to -0.3
Change From Baseline on the PUL Overall Score - Overall Baseline Week 89	-0.4 Units on a Scale Interval -2.0 to 1.1	-2.9 Units on a Scale Interval -7.0 to 1.2	-2.3 Units on a Scale Interval -4.5 to -0.1	-1.9 Units on a Scale Interval -3.5 to -0.3
Change From Baseline on the PUL Overall Score - Overall Baseline Baseline	66.3 Units on a Scale Interval 65.0 to 67.6	66.9 Units on a Scale Interval 64.7 to 69.0	66.9 Units on a Scale Interval 65.1 to 68.6	66.7 Units on a Scale Interval 65.7 to 67.6
Change From Baseline on the PUL Overall Score - Overall Baseline Week 9	-0.7 Units on a Scale Interval -2.0 to 0.5	0.5 Units on a Scale Interval -0.7 to 1.7	-0.1 Units on a Scale Interval -1.0 to 0.8	-0.1 Units on a Scale Interval -0.7 to 0.5
Change From Baseline on the PUL Overall Score - Overall Baseline Week 17	-0.5 Units on a Scale Interval -2.6 to 1.5	-0.2 Units on a Scale Interval -1.3 to 0.9	-0.4 Units on a Scale Interval -3.1 to 2.2	-0.4 Units on a Scale Interval -1.5 to 0.7
Change From Baseline on the PUL Overall Score - Overall Baseline Week 25	0.7 Units on a Scale Interval -1.1 to 2.4	0.3 Units on a Scale Interval -0.6 to 1.1	0.2 Units on a Scale Interval -1.5 to 1.8	0.4 Units on a Scale Interval -0.5 to 1.2
Change From Baseline on the PUL Overall Score - Overall Baseline Week 33	0.5 Units on a Scale Interval -0.8 to 1.9	-0.5 Units on a Scale Interval -2.4 to 1.4	-0.5 Units on a Scale Interval -1.7 to 0.7	-0.2 Units on a Scale Interval -1.0 to 0.7
Change From Baseline on the PUL Overall Score - Overall Baseline Week 41	-0.1 Units on a Scale Interval -2.1 to 2.0	-0.4 Units on a Scale Interval -1.9 to 1.2	-0.4 Units on a Scale Interval -1.9 to 1.2	-0.3 Units on a Scale Interval -1.2 to 0.7
Change From Baseline on the PUL Overall Score - Overall Baseline Week 49	0.1 Units on a Scale Interval -1.6 to 1.8	-0.8 Units on a Scale Interval -2.9 to 1.4	-0.5 Units on a Scale Interval -1.9 to 0.9	-0.4 Units on a Scale Interval -1.4 to 0.6
Change From Baseline on the PUL Overall Score - Overall Baseline Week 57	-0.3 Units on a Scale Interval -2.2 to 1.5	-0.8 Units on a Scale Interval -2.9 to 1.4	-4.7 Units on a Scale Interval -12.0 to 2.6	-2.0 Units on a Scale Interval -4.6 to 0.6
Change From Baseline on the PUL Overall Score - Overall Baseline Week 65	0.6 Units on a Scale Interval -1.0 to 2.2	-0.9 Units on a Scale Interval -3.0 to 1.3	-4.6 Units on a Scale Interval -11.6 to 2.5	-1.7 Units on a Scale Interval -4.2 to 0.8
Change From Baseline on the PUL Overall Score - Overall Baseline Week 73	-1.0 Units on a Scale Interval -2.9 to 0.9	-1.8 Units on a Scale Interval -4.5 to 0.9	-1.2 Units on a Scale Interval -3.3 to 1.0	-1.3 Units on a Scale Interval -2.6 to -0.1
Change From Baseline on the PUL Overall Score - Overall Baseline Week 81	-0.7 Units on a Scale Interval -2.5 to 1.1	-1.2 Units on a Scale Interval -3.7 to 1.4	-1.5 Units on a Scale Interval -3.7 to 0.6	-1.1 Units on a Scale Interval -2.3 to 0.1
Change From Baseline on the PUL Overall Score - Overall Baseline Week 97	-1.4 Units on a Scale Interval -3.9 to 1.0	-2.2 Units on a Scale Interval -5.3 to 0.9	-2.3 Units on a Scale Interval -5.1 to 0.4	-2.0 Units on a Scale Interval -3.5 to -0.5
Change From Baseline on the PUL Overall Score - Overall Baseline Week 110	-1.5 Units on a Scale Interval -3.7 to 0.7	-3.2 Units on a Scale Interval -6.7 to 0.2	-4.4 Units on a Scale Interval -8.5 to -0.4	-3.1 Units on a Scale Interval -5.0 to -1.3
Change From Baseline on the PUL Overall Score - Overall Baseline Week 146	-2.3 Units on a Scale Interval -7.4 to 2.9	-6.8 Units on a Scale Interval -15.3 to 1.6	-2.9 Units on a Scale Interval -7.7 to 2.0	-3.8 Units on a Scale Interval -6.7 to -0.9
Change From Baseline on the PUL Overall Score - Overall Baseline Week 170	-14.0 Units on a Scale Insufficient number of participants to calculate a 95% Confidence Interval.	-4.0 Units on a Scale Insufficient number of participants to calculate a 95% Confidence Interval.	-9.0 Units on a Scale Insufficient number of participants to calculate a 95% Confidence Interval.	-9.0 Units on a Scale Interval -17.8 to -0.2

SECONDARY outcome

Timeframe: Baseline, Weeks 13, 25, 49 and 73.

The 6MWD evaluated ambulation ability by measuring the distance walked in 6 minutes. In order to provide optimal testing conditions and consistency in endpoint measurements, the functional assessment of 6MWD was completed at approximately the same time of day. Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. Week 1 was counted starting from the study treatment in study B5161004.

Outcome measures

Outcome measures
Measure	Sequence 1 n=19 Participants In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 2 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 3 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Total n=59 Participants Sum of all participants in the study B5161004
Change From Baseline on the Six Minute Walk Distance (6MWD) - B5161004 Baseline Baseline	328.0 Meters Interval 266.5 to 389.5	386.2 Meters Interval 341.1 to 431.2	360.4 Meters Interval 305.1 to 415.6	356.5 Meters Interval 326.3 to 386.8
Change From Baseline on the Six Minute Walk Distance (6MWD) - B5161004 Baseline Week 13	-23.6 Meters Interval -50.0 to 2.8	-26.1 Meters Interval -45.6 to -6.5	-8.4 Meters Interval -28.6 to 11.9	-20.1 Meters Interval -32.5 to -7.7
Change From Baseline on the Six Minute Walk Distance (6MWD) - B5161004 Baseline Week 25	-45.5 Meters Interval -83.4 to -7.6	-16.1 Meters Interval -37.4 to 5.2	-11.3 Meters Interval -37.6 to 15.1	-25.2 Meters Interval -41.3 to -9.1
Change From Baseline on the Six Minute Walk Distance (6MWD) - B5161004 Baseline Week 49	-98.0 Meters Interval -219.5 to 23.5	-16.8 Meters Interval -55.2 to 21.6	-39.0 Meters Interval -68.2 to -9.8	-53.3 Meters Interval -92.8 to -13.8
Change From Baseline on the Six Minute Walk Distance (6MWD) - B5161004 Baseline Week 73	-110.0 Meters Insufficient number of participants to calculate a 95% Confidence Interval.	-41.5 Meters Insufficient number of participants to calculate a 95% Confidence Interval.	-22.0 Meters Insufficient number of participants to calculate a 95% Confidence Interval.	-65.0 Meters Interval -124.4 to -5.6

SECONDARY outcome

Timeframe: Baseline,Weeks 9,17,25,33,41,49,57,65,73,81,89,97,110,122,146,170.

The 6MWD evaluated ambulation ability by measuring the distance walked in 6 minutes. In order to provide optimal testing conditions and consistency in endpoint measurements, the functional assessment of 6MWD was completed at approximately the same time of day. This is the overall change from baseline which included the change since enrolling in the parent study B5161002. Overall baseline was defined as the last pre-dose assessment prior to the first day of dosing in study B5161002. Week 1 was start of the study treatment in parent study B5161002.

Outcome measures

Outcome measures
Measure	Sequence 1 n=19 Participants In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 2 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 3 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Total n=59 Participants Sum of all participants in the study B5161004
Change From Baseline on the 6MWD - Overall Baseline Week 122	-142.5 Meters Interval -229.0 to -56.1	-69.8 Meters Interval -144.7 to 5.0	-155.0 Meters Interval -231.0 to -79.0	-122.8 Meters Interval -165.6 to -80.0
Change From Baseline on the 6MWD - Overall Baseline Week 110	-115.5 Meters Interval -171.8 to -59.2	-87.9 Meters Interval -141.6 to -34.1	-126.1 Meters Interval -189.2 to -63.0	-109.4 Meters Interval -140.6 to -78.2
Change From Baseline on the 6MWD - Overall Baseline Baseline	409.1 Meters Interval 367.2 to 450.9	349.4 Meters Interval 290.3 to 408.5	363.7 Meters Interval 326.0 to 401.4	373.5 Meters Interval 347.0 to 399.9
Change From Baseline on the 6MWD - Overall Baseline Week 9	-11.6 Meters Interval -29.5 to 6.3	-2.0 Meters Interval -22.8 to 18.8	-9.3 Meters Interval -21.3 to 2.7	-7.8 Meters Interval -17.0 to 1.4
Change From Baseline on the 6MWD - Overall Baseline Week 17	-36.8 Meters Interval -63.9 to -9.7	-16.1 Meters Interval -39.2 to 7.1	-15.6 Meters Interval -34.8 to 3.6	-23.2 Meters Interval -36.2 to -10.2
Change From Baseline on the 6MWD - Overall Baseline Week 25	-41.8 Meters Interval -80.7 to -2.9	-8.2 Meters Interval -35.7 to 19.3	-29.6 Meters Interval -54.9 to -4.4	-26.2 Meters Interval -43.3 to -9.1
Change From Baseline on the 6MWD - Overall Baseline Week 33	-43.8 Meters Interval -74.2 to -13.5	-17.5 Meters Interval -45.8 to 10.8	-34.9 Meters Interval -62.3 to -7.5	-32.3 Meters Interval -48.1 to -16.4
Change From Baseline on the 6MWD - Overall Baseline Week 41	-54.2 Meters Interval -91.3 to -17.1	-37.4 Meters Interval -70.8 to -4.1	-34.9 Meters Interval -64.2 to -5.7	-42.4 Meters Interval -60.6 to -24.1
Change From Baseline on the 6MWD - Overall Baseline Week 49	-59.8 Meters Interval -96.8 to -22.9	-29.1 Meters Interval -64.2 to 6.0	-37.3 Meters Interval -65.9 to -8.8	-42.6 Meters Interval -61.4 to -23.8
Change From Baseline on the 6MWD - Overall Baseline Week 57	-72.2 Meters Interval -109.9 to -34.4	-32.8 Meters Interval -69.8 to 4.1	-52.6 Meters Interval -86.8 to -18.4	-53.4 Meters Interval -73.7 to -33.0
Change From Baseline on the 6MWD - Overall Baseline Week 65	-74.5 Meters Interval -128.9 to -20.0	-33.3 Meters Interval -71.1 to 4.5	-58.2 Meters Interval -106.3 to -10.0	-56.0 Meters Interval -82.2 to -29.8
Change From Baseline on the 6MWD - Overall Baseline Week 73	-77.2 Meters Interval -119.8 to -34.7	-35.5 Meters Interval -70.6 to -0.4	-60.1 Meters Interval -102.5 to -17.6	-58.4 Meters Interval -80.6 to -36.3
Change From Baseline on the 6MWD - Overall Baseline Week 81	-78.9 Meters Interval -120.5 to -37.3	-42.6 Meters Interval -94.7 to 9.5	-39.6 Meters Interval -64.4 to -14.7	-55.4 Meters Interval -78.0 to -32.7
Change From Baseline on the 6MWD - Overall Baseline Week 89	-96.7 Meters Interval -141.5 to -51.9	-33.7 Meters Interval -73.3 to 5.9	-41.5 Meters Interval -63.8 to -19.2	-60.6 Meters Interval -83.2 to -37.9
Change From Baseline on the 6MWD - Overall Baseline Week 97	-80.7 Meters Interval -131.4 to -30.1	-25.1 Meters Interval -64.0 to 13.9	-55.3 Meters Interval -79.3 to -31.3	-56.2 Meters Interval -79.8 to -32.6
Change From Baseline on the 6MWD - Overall Baseline Week 146	-224.0 Meters Interval -454.5 to 6.5	-53.2 Meters Interval -179.5 to 73.2	-137.1 Meters Interval -209.0 to -65.3	-138.1 Meters Interval -213.2 to -62.9
Change From Baseline on the 6MWD - Overall Baseline Week 170	-184.0 Meters Insufficient number of participants to calculate a 95% Confidence Interval.	-90.5 Meters Insufficient number of participants to calculate a 95% Confidence Interval.	-206.5 Meters Insufficient number of participants to calculate a 95% Confidence Interval.	-160.3 Meters Interval -294.3 to -26.4

SECONDARY outcome

Timeframe: Baseline, Weeks 13, 25, 49 and 73.

The FEV1 was recorded as an absolute volume in litres and in terms of predicted values according to age, height, race and gender. The best single FEV1 measurement from a set of 3 was recorded in the database. Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. Week 1 was counted starting from the study treatment in study B5161004.

Outcome measures

Outcome measures
Measure	Sequence 1 n=19 Participants In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 2 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 3 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Total n=59 Participants Sum of all participants in the study B5161004
Change From Baseline on the Forced Expiratory Volume in One Second (FEV1) - B5161004 Baseline FEV1 - Baseline	1.3694 Litres Interval 1.1372 to 1.6015	1.4235 Litres Interval 1.1693 to 1.6777	1.5335 Litres Interval 1.3687 to 1.6983	1.4436 Litres Interval 1.3243 to 1.5629
Change From Baseline on the Forced Expiratory Volume in One Second (FEV1) - B5161004 Baseline FEV1 - Week 13	0.1113 Litres Interval -0.0094 to 0.2319	0.1307 Litres Interval -0.004 to 0.2653	-0.0014 Litres Interval -0.1178 to 0.115	0.0827 Litres Interval 0.0144 to 0.1509
Change From Baseline on the Forced Expiratory Volume in One Second (FEV1) - B5161004 Baseline FEV1 - Week 25	0.1473 Litres Interval -0.0405 to 0.3351	0.1175 Litres Interval 0.0093 to 0.2257	0.0923 Litres Interval -0.0524 to 0.237	0.1175 Litres Interval 0.0406 to 0.1944
Change From Baseline on the Forced Expiratory Volume in One Second (FEV1) - B5161004 Baseline FEV1 - Week 49	0.3057 Litres Interval 0.0016 to 0.6098	0.2083 Litres Interval -0.0561 to 0.4728	0.1000 Litres Interval -0.0167 to 0.2167	0.2100 Litres Interval 0.0874 to 0.3326
Change From Baseline on the Forced Expiratory Volume in One Second (FEV1) - B5161004 Baseline FEV1 - Week 73	0.7500 Litres Insufficient number of participants to calculate a 95% Confidence Interval.	0.2550 Litres Insufficient number of participants to calculate a 95% Confidence Interval.	0.2800 Litres Insufficient number of participants to calculate a 95% Confidence Interval.	0.4580 Litres Interval -0.3052 to 1.2212

SECONDARY outcome

Timeframe: Baseline, Weeks 13, 25, 49 and 73.

PEFR was one of the Pulmonary Function Tests (PFTs). Three technically adequate peak expiratory flow rate (PEFR) maneuvers were performed and reported in Litres/Minute (L/min), and the highest single PEFR was reported in the database. In order to provide optimal testing conditions and consistency in endpoint measurements, the functional assessment of PEFR was completed at approximately the same time of day. Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. Week 1 was counted starting from the study treatment in study B5161004.

Outcome measures

Outcome measures
Measure	Sequence 1 n=19 Participants In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 2 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 3 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Total n=59 Participants Sum of all participants in the study B5161004
Change From Baseline on the Peak Expiratory Flow Rate (PEFR)- B5161004 Baseline Week 49	-31.171 L/min Interval -94.943 to 32.6	11.700 L/min Interval -55.267 to 78.667	50.967 L/min Interval -1.595 to 103.529	8.305 L/min Interval -24.489 to 41.099
Change From Baseline on the Peak Expiratory Flow Rate (PEFR)- B5161004 Baseline Baseline	200.314 L/min Interval 154.281 to 246.348	187.200 L/min Interval 150.135 to 224.265	185.882 L/min Interval 163.694 to 208.071	190.558 L/min Interval 171.737 to 209.38
Change From Baseline on the Peak Expiratory Flow Rate (PEFR)- B5161004 Baseline Week 13	-17.014 L/min Interval -56.536 to 22.507	20.613 L/min Interval -8.846 to 50.073	8.214 L/min Interval -29.197 to 45.626	4.326 L/min Interval -15.003 to 23.654
Change From Baseline on the Peak Expiratory Flow Rate (PEFR)- B5161004 Baseline Week 25	-16.260 L/min Interval -59.079 to 26.559	0.767 L/min Interval -22.311 to 23.845	39.250 L/min Interval 6.034 to 72.466	9.341 L/min Interval -9.379 to 28.061
Change From Baseline on the Peak Expiratory Flow Rate (PEFR)- B5161004 Baseline Week 73	6.800 L/min Insufficient number of participants to calculate a 95% Confidence Interval.	5.600 L/min Insufficient number of participants to calculate a 95% Confidence Interval.	36.000 L/min Insufficient number of participants to calculate a 95% Confidence Interval.	12.160 L/min Interval -81.893 to 106.213

SECONDARY outcome

Timeframe: Baseline, Weeks 13, 25, 49, 73.

Muscle strength was quantified by means of a handheld dynamometer. The following muscle groups were evaluated: knee extension, elbow flexion, elbow extension, hip abduction and shoulder abduction. 95% Confidence Interval was not calculated when less than or equal to 3 participants' data were available. Baseline was defined as the last assessment prior to dosing on Day 1 in B5161004. Week 1 was counted starting from the study treatment in study B5161004.

Outcome measures

Outcome measures
Measure	Sequence 1 n=19 Participants In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 2 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 3 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Total n=59 Participants Sum of all participants in the study B5161004
Change From Baseline on the Myometry Based Muscle Strength - B5161004 Baseline Shoulder Abduction - Left - Week 25	-0.29 Kilograms Interval -1.22 to 0.64	-0.53 Kilograms Interval -1.21 to 0.16	-0.44 Kilograms Interval -0.81 to -0.06	-0.42 Kilograms Interval -0.76 to -0.08
Change From Baseline on the Myometry Based Muscle Strength - B5161004 Baseline Shoulder Abduction - Left - Week 49	-0.44 Kilograms Interval -2.36 to 1.47	-0.45 Kilograms Interval -1.88 to 0.98	-0.50 Kilograms Interval -0.77 to -0.23	-0.47 Kilograms Interval -1.1 to 0.17
Change From Baseline on the Myometry Based Muscle Strength - B5161004 Baseline Elbow Extension-Left - Week 49	-0.66 Kilograms Interval -1.93 to 0.61	-0.47 Kilograms Interval -1.05 to 0.12	-0.23 Kilograms Interval -0.67 to 0.22	-0.45 Kilograms Interval -0.86 to -0.04
Change From Baseline on the Myometry Based Muscle Strength - B5161004 Baseline Elbow Extension-Right - Week 13	-0.23 Kilograms Interval -0.61 to 0.15	-0.42 Kilograms Interval -1.05 to 0.21	-0.27 Kilograms Interval -0.71 to 0.17	-0.31 Kilograms Interval -0.58 to -0.04
Change From Baseline on the Myometry Based Muscle Strength - B5161004 Baseline Elbow Extension-Left - Baseline	3.35 Kilograms Interval 2.47 to 4.23	3.24 Kilograms Interval 2.58 to 3.89	2.83 Kilograms Interval 2.13 to 3.52	3.13 Kilograms Interval 2.72 to 3.53
Change From Baseline on the Myometry Based Muscle Strength - B5161004 Baseline Elbow Extension-Left - Week 13	-0.21 Kilograms Interval -0.55 to 0.14	-0.55 Kilograms Interval -1.11 to 0.01	-0.31 Kilograms Interval -0.81 to 0.18	-0.36 Kilograms Interval -0.62 to -0.1
Change From Baseline on the Myometry Based Muscle Strength - B5161004 Baseline Elbow Extension-Left - Week 25	-0.44 Kilograms Interval -0.94 to 0.07	-0.38 Kilograms Interval -1.13 to 0.36	-0.09 Kilograms Interval -0.63 to 0.45	-0.29 Kilograms Interval -0.61 to 0.03
Change From Baseline on the Myometry Based Muscle Strength - B5161004 Baseline Elbow Extension-Left - Week 73	-1.15 Kilograms Insufficient number of participants to calculate a 95% Confidence Interval.	-0.95 Kilograms Insufficient number of participants to calculate a 95% Confidence Interval.	-0.10 Kilograms Insufficient number of participants to calculate a 95% Confidence Interval.	-0.73 Kilograms Interval -1.46 to 0.0
Change From Baseline on the Myometry Based Muscle Strength - B5161004 Baseline Elbow Extension-Right - Baseline	3.31 Kilograms Interval 2.36 to 4.26	3.24 Kilograms Interval 2.53 to 3.95	2.94 Kilograms Interval 2.29 to 3.6	3.16 Kilograms Interval 2.74 to 3.57
Change From Baseline on the Myometry Based Muscle Strength - B5161004 Baseline Elbow Extension-Right - Week 25	-0.40 Kilograms Interval -1.05 to 0.25	-0.68 Kilograms Interval -1.21 to -0.14	0.06 Kilograms Interval -0.41 to 0.53	-0.31 Kilograms Interval -0.61 to -0.01
Change From Baseline on the Myometry Based Muscle Strength - B5161004 Baseline Elbow Extension-Right - Week 49	-0.59 Kilograms Interval -1.82 to 0.65	-0.60 Kilograms Interval -1.07 to -0.13	-0.07 Kilograms Interval -0.55 to 0.41	-0.41 Kilograms Interval -0.82 to 0.0
Change From Baseline on the Myometry Based Muscle Strength - B5161004 Baseline Elbow Extension-Right - Week 73	-0.70 Kilograms Insufficient number of participants to calculate a 95% Confidence Interval.	-1.25 Kilograms Insufficient number of participants to calculate a 95% Confidence Interval.	0.20 Kilograms Insufficient number of participants to calculate a 95% Confidence Interval.	-0.58 Kilograms Interval -1.35 to 0.18
Change From Baseline on the Myometry Based Muscle Strength - B5161004 Baseline Elbow Flexion-Left - Baseline	4.14 Kilograms Interval 2.79 to 5.49	3.74 Kilograms Interval 3.01 to 4.46	3.19 Kilograms Interval 2.5 to 3.88	3.67 Kilograms Interval 3.15 to 4.19
Change From Baseline on the Myometry Based Muscle Strength - B5161004 Baseline Elbow Flexion-Left - Week 13	-0.49 Kilograms Interval -1.15 to 0.17	-0.22 Kilograms Interval -0.92 to 0.49	-0.36 Kilograms Interval -0.85 to 0.12	-0.35 Kilograms Interval -0.69 to -0.02
Change From Baseline on the Myometry Based Muscle Strength - B5161004 Baseline Elbow Flexion-Left - Week 25	-0.65 Kilograms Interval -1.5 to 0.21	-0.58 Kilograms Interval -1.69 to 0.52	-0.19 Kilograms Interval -0.54 to 0.15	-0.45 Kilograms Interval -0.87 to -0.04
Change From Baseline on the Myometry Based Muscle Strength - B5161004 Baseline Elbow Flexion-Left - Week 49	-1.13 Kilograms Interval -2.97 to 0.71	-0.08 Kilograms Interval -1.33 to 1.16	-0.39 Kilograms Interval -1.1 to 0.33	-0.56 Kilograms Interval -1.22 to 0.11
Change From Baseline on the Myometry Based Muscle Strength - B5161004 Baseline Elbow Flexion-Left - Week 73	-1.25 Kilograms Insufficient number of participants to calculate a 95% Confidence Interval.	-1.55 Kilograms Insufficient number of participants to calculate a 95% Confidence Interval.	-0.05 Kilograms Insufficient number of participants to calculate a 95% Confidence Interval.	-0.95 Kilograms Interval -2.09 to 0.19
Change From Baseline on the Myometry Based Muscle Strength - B5161004 Baseline Elbow Flexion - Right - Baseline	4.13 Kilograms Interval 2.85 to 5.4	4.18 Kilograms Interval 3.33 to 5.02	3.07 Kilograms Interval 2.45 to 3.69	3.77 Kilograms Interval 3.25 to 4.28
Change From Baseline on the Myometry Based Muscle Strength - B5161004 Baseline Elbow Flexion - Right - Week 13	-0.48 Kilograms Interval -1.15 to 0.2	-0.85 Kilograms Interval -1.53 to -0.17	-0.18 Kilograms Interval -0.5 to 0.14	-0.50 Kilograms Interval -0.82 to -0.18
Change From Baseline on the Myometry Based Muscle Strength - B5161004 Baseline Elbow Flexion - Right - Week 25	-0.75 Kilograms Interval -2.03 to 0.53	-1.08 Kilograms Interval -2.04 to -0.11	0.32 Kilograms Interval -0.03 to 0.67	-0.44 Kilograms Interval -0.93 to 0.05
Change From Baseline on the Myometry Based Muscle Strength - B5161004 Baseline Elbow Flexion - Right - Week 49	-0.49 Kilograms Interval -1.89 to 0.92	-1.27 Kilograms Interval -2.25 to -0.29	-0.36 Kilograms Interval -0.62 to -0.1	-0.68 Kilograms Interval -1.18 to -0.17
Change From Baseline on the Myometry Based Muscle Strength - B5161004 Baseline Elbow Flexion - Right - Week 73	-1.25 Kilograms Insufficient number of participants to calculate a 95% Confidence Interval.	-1.20 Kilograms Insufficient number of participants to calculate a 95% Confidence Interval.	-0.70 Kilograms Insufficient number of participants to calculate a 95% Confidence Interval.	-1.05 Kilograms Interval -1.46 to -0.64
Change From Baseline on the Myometry Based Muscle Strength - B5161004 Baseline Hip Abduction - Left - Baseline	4.23 Kilograms Interval 2.91 to 5.54	5.29 Kilograms Interval 4.32 to 6.25	4.92 Kilograms Interval 4.28 to 5.57	4.82 Kilograms Interval 4.28 to 5.37
Change From Baseline on the Myometry Based Muscle Strength - B5161004 Baseline Hip Abduction - Left - Week 13	0.06 Kilograms Interval -0.4 to 0.51	-0.46 Kilograms Interval -1.43 to 0.5	-0.26 Kilograms Interval -1.19 to 0.67	-0.23 Kilograms Interval -0.67 to 0.22
Change From Baseline on the Myometry Based Muscle Strength - B5161004 Baseline Hip Abduction - Left - Week 25	-0.08 Kilograms Interval -1.38 to 1.22	-0.75 Kilograms Interval -1.63 to 0.13	-0.11 Kilograms Interval -0.78 to 0.56	-0.32 Kilograms Interval -0.81 to 0.17
Change From Baseline on the Myometry Based Muscle Strength - B5161004 Baseline Hip Abduction - Left - Week 49	-0.81 Kilograms Interval -3.04 to 1.41	-0.94 Kilograms Interval -1.98 to 0.1	0.00 Kilograms Interval -0.72 to 0.72	-0.55 Kilograms Interval -1.3 to 0.21
Change From Baseline on the Myometry Based Muscle Strength - B5161004 Baseline Hip Abduction - Left - Week 73	-0.75 Kilograms Insufficient number of participants to calculate a 95% Confidence Interval.	-2.20 Kilograms Insufficient number of participants to calculate a 95% Confidence Interval.	0.30 Kilograms Insufficient number of participants to calculate a 95% Confidence Interval.	-1.12 Kilograms Interval -2.83 to 0.59
Change From Baseline on the Myometry Based Muscle Strength - B5161004 Baseline Hip Abduction - Right - Baseline	4.39 Kilograms Interval 2.8 to 5.98	5.55 Kilograms Interval 4.44 to 6.67	4.99 Kilograms Interval 4.23 to 5.75	4.99 Kilograms Interval 4.34 to 5.64
Change From Baseline on the Myometry Based Muscle Strength - B5161004 Baseline Hip Abduction - Right - Week 13	-0.04 Kilograms Interval -0.59 to 0.52	-0.75 Kilograms Interval -1.94 to 0.43	-0.51 Kilograms Interval -1.42 to 0.41	-0.44 Kilograms Interval -0.95 to 0.07
Change From Baseline on the Myometry Based Muscle Strength - B5161004 Baseline Hip Abduction - Right - Week 25	-0.10 Kilograms Interval -1.77 to 1.57	-0.94 Kilograms Interval -2.44 to 0.56	-0.52 Kilograms Interval -1.54 to 0.51	-0.54 Kilograms Interval -1.26 to 0.18
Change From Baseline on the Myometry Based Muscle Strength - B5161004 Baseline Hip Abduction - Right - Week 49	-1.10 Kilograms Interval -3.88 to 1.68	-0.66 Kilograms Interval -2.74 to 1.42	0.01 Kilograms Interval -1.33 to 1.36	-0.57 Kilograms Interval -1.61 to 0.46
Change From Baseline on the Myometry Based Muscle Strength - B5161004 Baseline Hip Abduction - Right - Week 73	-0.30 Kilograms Insufficient number of participants to calculate a 95% Confidence Interval.	-2.15 Kilograms Insufficient number of participants to calculate a 95% Confidence Interval.	0.30 Kilograms Insufficient number of participants to calculate a 95% Confidence Interval.	-0.92 Kilograms Interval -3.05 to 1.21
Change From Baseline on the Myometry Based Muscle Strength - B5161004 Baseline Knee Extension - Left - Baseline	4.21 Kilograms Interval 3.01 to 5.4	4.54 Kilograms Interval 3.4 to 5.68	4.59 Kilograms Interval 3.1 to 6.08	4.45 Kilograms Interval 3.76 to 5.15
Change From Baseline on the Myometry Based Muscle Strength - B5161004 Baseline Knee Extension - Left - Week 13	-0.34 Kilograms Interval -0.99 to 0.3	-0.44 Kilograms Interval -1.28 to 0.4	-1.02 Kilograms Interval -1.85 to -0.19	-0.61 Kilograms Interval -1.04 to -0.18
Change From Baseline on the Myometry Based Muscle Strength - B5161004 Baseline Knee Extension - Left - Week 25	-0.60 Kilograms Interval -1.37 to 0.17	-0.73 Kilograms Interval -1.85 to 0.38	-0.92 Kilograms Interval -1.66 to -0.18	-0.76 Kilograms Interval -1.23 to -0.3
Change From Baseline on the Myometry Based Muscle Strength - B5161004 Baseline Knee Extension - Left - Week 49	-0.34 Kilograms Interval -1.15 to 0.46	-0.07 Kilograms Interval -0.88 to 0.74	-0.54 Kilograms Interval -1.51 to 0.43	-0.33 Kilograms Interval -0.74 to 0.08
Change From Baseline on the Myometry Based Muscle Strength - B5161004 Baseline Knee Extension - Left - Week 73	-0.60 Kilograms Insufficient number of participants to calculate a 95% Confidence Interval.	0.00 Kilograms Insufficient number of participants to calculate a 95% Confidence Interval.	-0.25 Kilograms Insufficient number of participants to calculate a 95% Confidence Interval.	-0.28 Kilograms Interval -0.76 to 0.19
Change From Baseline on the Myometry Based Muscle Strength - B5161004 Baseline Knee Extension - Right - Baseline	4.33 Kilograms Interval 3.09 to 5.58	4.48 Kilograms Interval 3.53 to 5.44	4.81 Kilograms Interval 3.16 to 6.46	4.55 Kilograms Interval 3.83 to 5.27
Change From Baseline on the Myometry Based Muscle Strength - B5161004 Baseline Knee Extension - Right - Week 13	-0.35 Kilograms Interval -1.26 to 0.56	-0.13 Kilograms Interval -0.89 to 0.63	-0.93 Kilograms Interval -1.82 to -0.03	-0.47 Kilograms Interval -0.94 to 0.0
Change From Baseline on the Myometry Based Muscle Strength - B5161004 Baseline Knee Extension - Right - Week 25	-0.35 Kilograms Interval -1.1 to 0.39	-1.08 Kilograms Interval -1.8 to -0.36	-0.94 Kilograms Interval -1.71 to -0.16	-0.81 Kilograms Interval -1.22 to -0.41
Change From Baseline on the Myometry Based Muscle Strength - B5161004 Baseline Knee Extension - Right - Week 49	-0.74 Kilograms Interval -1.71 to 0.22	-0.23 Kilograms Interval -1.64 to 1.18	-0.69 Kilograms Interval -2.33 to 0.96	-0.57 Kilograms Interval -1.21 to 0.07
Change From Baseline on the Myometry Based Muscle Strength - B5161004 Baseline Knee Extension - Right - Week 73	-0.45 Kilograms Insufficient number of participants to calculate a 95% Confidence Interval.	-1.35 Kilograms Insufficient number of participants to calculate a 95% Confidence Interval.	-0.45 Kilograms Insufficient number of participants to calculate a 95% Confidence Interval.	-0.75 Kilograms Interval -1.72 to 0.22
Change From Baseline on the Myometry Based Muscle Strength - B5161004 Baseline Shoulder Abduction - Left - Baseline	3.83 Kilograms Interval 2.83 to 4.83	3.95 Kilograms Interval 3.37 to 4.52	3.75 Kilograms Interval 3.08 to 4.42	3.84 Kilograms Interval 3.44 to 4.25
Change From Baseline on the Myometry Based Muscle Strength - B5161004 Baseline Shoulder Abduction - Left - Week 13	-0.14 Kilograms Interval -0.71 to 0.43	-0.31 Kilograms Interval -0.95 to 0.34	-0.28 Kilograms Interval -0.69 to 0.14	-0.24 Kilograms Interval -0.54 to 0.05
Change From Baseline on the Myometry Based Muscle Strength - B5161004 Baseline Shoulder Abduction - Left - Week 73	-0.75 Kilograms Insufficient number of participants to calculate a 95% Confidence Interval.	-1.30 Kilograms Insufficient number of participants to calculate a 95% Confidence Interval.	0.20 Kilograms Insufficient number of participants to calculate a 95% Confidence Interval.	-0.62 Kilograms Interval -1.84 to 0.61
Change From Baseline on the Myometry Based Muscle Strength - B5161004 Baseline Shoulder Abduction - Right - Baseline	3.99 Kilograms Interval 2.72 to 5.26	4.26 Kilograms Interval 3.29 to 5.23	3.91 Kilograms Interval 3.1 to 4.71	4.05 Kilograms Interval 3.51 to 4.6
Change From Baseline on the Myometry Based Muscle Strength - B5161004 Baseline Shoulder Abduction - Right - Week 13	-0.16 Kilograms Interval -0.75 to 0.44	-0.55 Kilograms Interval -1.5 to 0.4	-0.39 Kilograms Interval -0.96 to 0.18	-0.37 Kilograms Interval -0.76 to 0.02
Change From Baseline on the Myometry Based Muscle Strength - B5161004 Baseline Shoulder Abduction - Right - Week 25	-0.05 Kilograms Interval -1.02 to 0.91	-0.81 Kilograms Interval -1.89 to 0.27	-0.59 Kilograms Interval -1.34 to 0.16	-0.50 Kilograms Interval -0.99 to -0.01
Change From Baseline on the Myometry Based Muscle Strength - B5161004 Baseline Shoulder Abduction - Right - Week 49	-0.49 Kilograms Interval -2.95 to 1.98	-0.60 Kilograms Interval -1.78 to 0.58	-0.16 Kilograms Interval -0.58 to 0.27	-0.41 Kilograms Interval -1.17 to 0.36
Change From Baseline on the Myometry Based Muscle Strength - B5161004 Baseline Shoulder Abduction - Right - Week 73	-0.30 Kilograms Insufficient number of participants to calculate a 95% Confidence Interval.	-1.55 Kilograms Insufficient number of participants to calculate a 95% Confidence Interval.	-0.60 Kilograms Insufficient number of participants to calculate a 95% Confidence Interval.	-0.82 Kilograms Interval -1.51 to -0.12

SECONDARY outcome

Timeframe: Baseline,Weeks 9,17,25,33,41,49,57,65,73,81,89,97,110,122,146,170.

Muscle strength was quantified by means of a handheld dynamometer. The following muscle groups were evaluated: knee extension, elbow flexion, elbow extension, hip abduction and shoulder abduction. 95% Confidence Interval was not calculated when less than or equal to 3 participants' data were available. Overall baseline was defined as the last pre-dose assessment prior to the first day of dosing in study B5161002. Week 1 was start of the study treatment in parent study B5161002.

Outcome measures

Outcome measures
Measure	Sequence 1 n=19 Participants In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 2 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 3 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Total n=59 Participants Sum of all participants in the study B5161004
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Elbow Flexion-Left - Week 9	-0.11 Kilograms Interval -1.17 to 0.95	1.06 Kilograms Interval -0.01 to 2.14	0.01 Kilograms Interval -0.46 to 0.47	0.32 Kilograms Interval -0.18 to 0.82
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Knee Extension-Right - Week 146	-3.21 Kilograms Interval -7.01 to 0.58	-1.13 Kilograms Interval -2.61 to 0.34	-0.56 Kilograms Interval -1.86 to 0.75	-1.66 Kilograms Interval -2.97 to -0.35
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Knee Extension-Left - Week 89	-2.16 Kilograms Interval -3.98 to -0.33	-1.45 Kilograms Interval -2.46 to -0.43	-0.27 Kilograms Interval -1.16 to 0.61	-1.28 Kilograms Interval -2.0 to -0.56
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Knee Extension-Left - Week 97	-1.80 Kilograms Interval -3.65 to 0.05	-1.24 Kilograms Interval -2.41 to -0.07	-0.82 Kilograms Interval -1.93 to 0.3	-1.28 Kilograms Interval -2.04 to -0.51
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Elbow Flexion-Right - Week 33	-0.56 Kilograms Interval -1.57 to 0.46	-0.36 Kilograms Interval -1.0 to 0.29	0.06 Kilograms Interval -0.4 to 0.52	-0.28 Kilograms Interval -0.68 to 0.12
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Shoulder Abduction-Right - Week 110	-0.25 Kilograms Interval -1.35 to 0.85	-0.86 Kilograms Interval -1.93 to 0.21	-0.08 Kilograms Interval -0.63 to 0.48	-0.40 Kilograms Interval -0.91 to 0.11
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Shoulder Abduction-Right - Week 122	-0.68 Kilograms Interval -2.21 to 0.85	-0.66 Kilograms Interval -1.53 to 0.22	0.14 Kilograms Interval -0.51 to 0.79	-0.36 Kilograms Interval -0.91 to 0.18
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Shoulder Abduction-Right - Week 146	-1.50 Kilograms Interval -3.96 to 0.96	-0.75 Kilograms Interval -1.89 to 0.39	0.19 Kilograms Interval -0.44 to 0.81	-0.69 Kilograms Interval -1.52 to 0.15
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Hip Abduction-Right - Week 170	-4.30 Kilograms Insufficient number of participants to calculate a 95% Confidence Interval.	-1.75 Kilograms Insufficient number of participants to calculate a 95% Confidence Interval.	1.60 Kilograms Insufficient number of participants to calculate a 95% Confidence Interval.	-2.10 Kilograms Interval -5.12 to 0.92
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Knee Extension-Left - Baseline	5.99 Kilograms Interval 4.01 to 7.98	5.38 Kilograms Interval 4.01 to 6.74	5.21 Kilograms Interval 3.53 to 6.88	5.52 Kilograms Interval 4.6 to 6.43
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Knee Extension-Left - Week 9	-0.54 Kilograms Interval -1.56 to 0.48	1.20 Kilograms Interval -0.24 to 2.64	-0.16 Kilograms Interval -0.81 to 0.49	0.16 Kilograms Interval -0.45 to 0.77
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Knee Extension-Left - Week 17	-0.88 Kilograms Interval -2.29 to 0.53	0.17 Kilograms Interval -0.95 to 1.29	-0.12 Kilograms Interval -0.77 to 0.54	-0.27 Kilograms Interval -0.88 to 0.33
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Knee Extension-Left - Week 25	-1.66 Kilograms Interval -2.98 to -0.34	-0.14 Kilograms Interval -1.37 to 1.09	-0.38 Kilograms Interval -0.84 to 0.07	-0.72 Kilograms Interval -1.33 to -0.11
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Knee Extension-Left - Week 33	-1.35 Kilograms Interval -3.13 to 0.43	-0.54 Kilograms Interval -1.41 to 0.33	-0.55 Kilograms Interval -1.19 to 0.1	-0.81 Kilograms Interval -1.46 to -0.16
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Knee Extension-Left - Week 41	-1.53 Kilograms Interval -3.47 to 0.41	-0.87 Kilograms Interval -1.84 to 0.11	-0.67 Kilograms Interval -1.14 to -0.21	-1.00 Kilograms Interval -1.66 to -0.34
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Knee Extension-Left - Week 49	-1.27 Kilograms Interval -3.24 to 0.71	-0.59 Kilograms Interval -1.48 to 0.3	-0.85 Kilograms Interval -1.5 to -0.2	-0.90 Kilograms Interval -1.6 to -0.19
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Knee Extension-Left - Week 57	-1.67 Kilograms Interval -3.5 to 0.16	-0.77 Kilograms Interval -1.8 to 0.27	-0.73 Kilograms Interval -1.79 to 0.32	-1.06 Kilograms Interval -1.8 to -0.31
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Knee Extension-Left - Week 65	-1.23 Kilograms Interval -2.88 to 0.41	-0.46 Kilograms Interval -1.68 to 0.76	-0.42 Kilograms Interval -1.31 to 0.47	-0.69 Kilograms Interval -1.39 to 0.01
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Knee Extension-Left - Week 73	-1.78 Kilograms Interval -3.77 to 0.21	-0.39 Kilograms Interval -1.85 to 1.07	-0.02 Kilograms Interval -0.57 to 0.53	-0.69 Kilograms Interval -1.48 to 0.1
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Knee Extension-Left - Week 81	-1.99 Kilograms Interval -3.74 to -0.25	-1.52 Kilograms Interval -2.51 to -0.53	-0.23 Kilograms Interval -1.03 to 0.58	-1.23 Kilograms Interval -1.93 to -0.53
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Knee Extension-Left - Week 110	-2.28 Kilograms Interval -4.26 to -0.3	-1.79 Kilograms Interval -3.16 to -0.42	-1.89 Kilograms Interval -3.18 to -0.6	-1.98 Kilograms Interval -2.82 to -1.15
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Knee Extension-Left - Week 122	-3.31 Kilograms Interval -6.35 to -0.27	-2.03 Kilograms Interval -3.46 to -0.59	-1.04 Kilograms Interval -1.63 to -0.46	-2.04 Kilograms Interval -3.01 to -1.06
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Knee Extension-Left - Week 146	-3.36 Kilograms Interval -8.02 to 1.31	-0.83 Kilograms Interval -1.93 to 0.26	-0.57 Kilograms Interval -1.5 to 0.36	-1.63 Kilograms Interval -3.13 to -0.12
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Knee Extension-Left - Week 170	-7.10 Kilograms Insufficient number of participants to calculate a 95% Confidence Interval.	-0.45 Kilograms Insufficient number of participants to calculate a 95% Confidence Interval.	-0.30 Kilograms Insufficient number of participants to calculate a 95% Confidence Interval.	-2.62 Kilograms Interval -6.43 to 1.2
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Knee Extension-Right - Baseline	6.12 Kilograms Interval 4.21 to 8.04	5.91 Kilograms Interval 4.43 to 7.39	5.08 Kilograms Interval 3.31 to 6.85	5.70 Kilograms Interval 4.76 to 6.64
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Knee Extension-Right - Week 9	-0.24 Kilograms Interval -1.37 to 0.88	1.02 Kilograms Interval -0.49 to 2.53	0.08 Kilograms Interval -0.51 to 0.66	0.28 Kilograms Interval -0.34 to 0.9
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Knee Extension-Right - Week 17	-0.70 Kilograms Interval -1.86 to 0.46	-0.26 Kilograms Interval -1.33 to 0.81	-0.16 Kilograms Interval -0.85 to 0.53	-0.37 Kilograms Interval -0.91 to 0.17
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Knee Extension-Right - Week 25	-1.27 Kilograms Interval -2.92 to 0.37	-0.71 Kilograms Interval -2.06 to 0.64	-0.21 Kilograms Interval -0.82 to 0.4	-0.72 Kilograms Interval -1.42 to -0.03
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Knee Extension-Right - Week 33	-0.74 Kilograms Interval -2.63 to 1.15	-0.91 Kilograms Interval -1.94 to 0.12	-0.39 Kilograms Interval -1.08 to 0.31	-0.68 Kilograms Interval -1.39 to 0.02
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Knee Extension-Right - Week 41	-1.16 Kilograms Interval -3.13 to 0.8	-1.07 Kilograms Interval -2.19 to 0.05	-0.28 Kilograms Interval -0.96 to 0.4	-0.83 Kilograms Interval -1.54 to -0.12
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Knee Extension-Right - Week 49	-1.23 Kilograms Interval -3.1 to 0.65	-1.04 Kilograms Interval -2.0 to -0.08	-0.34 Kilograms Interval -0.9 to 0.22	-0.87 Kilograms Interval -1.55 to -0.19
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Knee Extension-Right - Week 57	-1.44 Kilograms Interval -3.16 to 0.28	-1.16 Kilograms Interval -2.24 to -0.08	-0.69 Kilograms Interval -1.45 to 0.06	-1.11 Kilograms Interval -1.79 to -0.42
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Knee Extension-Right - Week 65	-1.28 Kilograms Interval -2.84 to 0.28	-1.12 Kilograms Interval -2.44 to 0.2	-0.26 Kilograms Interval -1.39 to 0.87	-0.89 Kilograms Interval -1.63 to -0.15
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Knee Extension-Right - Week 73	-1.57 Kilograms Interval -3.28 to 0.14	-1.24 Kilograms Interval -2.55 to 0.08	0.15 Kilograms Interval -0.41 to 0.7	-0.87 Kilograms Interval -1.59 to -0.16
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Knee Extension-Right - Week 81	-1.82 Kilograms Interval -3.37 to -0.26	-1.97 Kilograms Interval -3.11 to -0.84	0.08 Kilograms Interval -0.67 to 0.82	-1.22 Kilograms Interval -1.9 to -0.53
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Knee Extension-Right - Week 89	-2.05 Kilograms Interval -3.88 to -0.22	-1.80 Kilograms Interval -2.83 to -0.76	-0.21 Kilograms Interval -0.87 to 0.45	-1.35 Kilograms Interval -2.05 to -0.64
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Knee Extension-Right - Week 97	-1.73 Kilograms Interval -3.43 to -0.02	-1.79 Kilograms Interval -2.95 to -0.62	-0.44 Kilograms Interval -1.87 to 1.0	-1.31 Kilograms Interval -2.11 to -0.51
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Knee Extension-Right - Week 110	-2.21 Kilograms Interval -3.84 to -0.58	-2.05 Kilograms Interval -3.48 to -0.63	-1.42 Kilograms Interval -2.72 to -0.12	-1.89 Kilograms Interval -2.67 to -1.11
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Knee Extension-Right - Week 122	-2.77 Kilograms Interval -5.29 to -0.26	-2.78 Kilograms Interval -4.36 to -1.19	-0.44 Kilograms Interval -1.19 to 0.31	-1.89 Kilograms Interval -2.82 to -0.97
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Knee Extension-Right - Week 170	-7.35 Kilograms Insufficient number of participants to calculate a 95% Confidence Interval.	-2.00 Kilograms Insufficient number of participants to calculate a 95% Confidence Interval.	-0.75 Kilograms Insufficient number of participants to calculate a 95% Confidence Interval.	-3.37 Kilograms Interval -6.71 to -0.02
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Shoulder Abduction-Left - Baseline	3.55 Kilograms Interval 2.66 to 4.45	4.24 Kilograms Interval 3.26 to 5.22	3.44 Kilograms Interval 2.71 to 4.17	3.75 Kilograms Interval 3.26 to 4.23
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Shoulder Abduction-Right - Week 170	-4.35 Kilograms Insufficient number of participants to calculate a 95% Confidence Interval.	-0.90 Kilograms Insufficient number of participants to calculate a 95% Confidence Interval.	-0.20 Kilograms Insufficient number of participants to calculate a 95% Confidence Interval.	-1.82 Kilograms Interval -3.95 to 0.31
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Elbow Flexion-Right - Week 41	-0.60 Kilograms Interval -1.9 to 0.7	-0.29 Kilograms Interval -0.95 to 0.38	-0.26 Kilograms Interval -0.7 to 0.18	-0.38 Kilograms Interval -0.85 to 0.09
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Elbow Flexion-Right - Week 49	-0.73 Kilograms Interval -1.74 to 0.28	-0.66 Kilograms Interval -1.24 to -0.07	-0.01 Kilograms Interval -0.48 to 0.47	-0.47 Kilograms Interval -0.87 to -0.07
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Elbow Flexion-Right - Week 57	-1.11 Kilograms Interval -2.15 to -0.07	-0.42 Kilograms Interval -0.97 to 0.13	-0.23 Kilograms Interval -0.65 to 0.19	-0.58 Kilograms Interval -0.98 to -0.18
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Elbow Flexion-Right - Week 65	-0.77 Kilograms Interval -1.72 to 0.18	-0.33 Kilograms Interval -1.09 to 0.43	-0.06 Kilograms Interval -0.5 to 0.37	-0.39 Kilograms Interval -0.8 to 0.02
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Elbow Flexion-Right - Week 73	-0.93 Kilograms Interval -1.8 to -0.06	-0.31 Kilograms Interval -1.03 to 0.41	-0.11 Kilograms Interval -0.68 to 0.46	-0.44 Kilograms Interval -0.85 to -0.04
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Elbow Flexion-Right - Week 81	-0.99 Kilograms Interval -1.87 to -0.12	-0.30 Kilograms Interval -0.96 to 0.36	0.03 Kilograms Interval -0.48 to 0.53	-0.42 Kilograms Interval -0.81 to -0.02
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Elbow Flexion-Right - Week 89	-0.87 Kilograms Interval -1.77 to 0.04	-0.58 Kilograms Interval -1.18 to 0.02	-0.17 Kilograms Interval -0.59 to 0.25	-0.53 Kilograms Interval -0.9 to -0.17
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Elbow Flexion-Right - Week 97	-0.86 Kilograms Interval -1.93 to 0.2	-0.35 Kilograms Interval -1.13 to 0.44	-0.57 Kilograms Interval -1.19 to 0.06	-0.59 Kilograms Interval -1.04 to -0.13
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Elbow Flexion-Right - Week 110	-1.30 Kilograms Interval -2.44 to -0.16	-1.22 Kilograms Interval -2.29 to -0.16	-0.85 Kilograms Interval -1.46 to -0.25	-1.12 Kilograms Interval -1.64 to -0.61
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Elbow Flexion-Right - Week 122	-2.34 Kilograms Interval -4.28 to -0.4	-0.91 Kilograms Interval -2.08 to 0.27	-0.06 Kilograms Interval -0.65 to 0.52	-0.98 Kilograms Interval -1.67 to -0.28
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Elbow Flexion-Right - Week 146	-2.00 Kilograms Interval -4.72 to 0.72	-0.90 Kilograms Interval -2.0 to 0.2	-0.63 Kilograms Interval -1.26 to 0.0	-1.19 Kilograms Interval -2.07 to -0.31
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Elbow Flexion-Right - Week 170	-5.35 Kilograms Insufficient number of participants to calculate a 95% Confidence Interval.	-1.20 Kilograms Insufficient number of participants to calculate a 95% Confidence Interval.	-1.15 Kilograms Insufficient number of participants to calculate a 95% Confidence Interval.	-2.57 Kilograms Interval -4.87 to -0.26
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Hip Abduction-Left - Baseline	4.31 Kilograms Interval 3.23 to 5.38	5.10 Kilograms Interval 3.84 to 6.36	4.35 Kilograms Interval 3.56 to 5.13	4.59 Kilograms Interval 4.01 to 5.17
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Hip Abduction-Left - Week 9	0.23 Kilograms Interval -0.86 to 1.32	1.19 Kilograms Interval 0.17 to 2.21	0.38 Kilograms Interval -0.25 to 1.01	0.60 Kilograms Interval 0.08 to 1.11
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Hip Abduction-Left - Week 17	0.36 Kilograms Interval -0.94 to 1.65	-0.03 Kilograms Interval -1.1 to 1.04	0.74 Kilograms Interval 0.1 to 1.37	0.36 Kilograms Interval -0.2 to 0.92
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Hip Abduction-Left - Week 25	-0.49 Kilograms Interval -1.85 to 0.87	0.41 Kilograms Interval -0.76 to 1.58	0.52 Kilograms Interval -0.13 to 1.16	0.15 Kilograms Interval -0.46 to 0.76
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Hip Abduction-Left - Week 33	0.18 Kilograms Interval -1.16 to 1.51	0.13 Kilograms Interval -0.85 to 1.11	0.26 Kilograms Interval -0.47 to 0.99	0.19 Kilograms Interval -0.38 to 0.75
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Hip Abduction-Left - Week 41	-0.64 Kilograms Interval -1.66 to 0.37	-0.19 Kilograms Interval -1.14 to 0.77	0.59 Kilograms Interval -0.08 to 1.27	-0.06 Kilograms Interval -0.56 to 0.44
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Hip Abduction-Left - Week 49	0.56 Kilograms Interval -1.16 to 2.27	-0.47 Kilograms Interval -1.27 to 0.34	0.55 Kilograms Interval -0.29 to 1.38	0.20 Kilograms Interval -0.45 to 0.85
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Hip Abduction-Left - Week 57	-0.16 Kilograms Interval -1.11 to 0.79	-0.06 Kilograms Interval -0.89 to 0.77	0.62 Kilograms Interval -0.06 to 1.29	0.12 Kilograms Interval -0.34 to 0.58
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Hip Abduction-Left - Week 65	-0.24 Kilograms Interval -1.19 to 0.71	-0.06 Kilograms Interval -1.1 to 0.98	0.86 Kilograms Interval 0.03 to 1.68	0.18 Kilograms Interval -0.35 to 0.71
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Hip Abduction-Left - Week 73	0.00 Kilograms Interval -1.04 to 1.04	0.31 Kilograms Interval -0.81 to 1.43	1.06 Kilograms Interval 0.07 to 2.04	0.47 Kilograms Interval -0.11 to 1.05
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Hip Abduction-Left - Week 81	-0.43 Kilograms Interval -1.32 to 0.46	0.17 Kilograms Interval -0.91 to 1.26	1.35 Kilograms Interval 0.63 to 2.06	0.38 Kilograms Interval -0.15 to 0.91
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Hip Abduction-Left - Week 89	0.37 Kilograms Interval -0.64 to 1.38	0.14 Kilograms Interval -0.86 to 1.13	0.78 Kilograms Interval -0.01 to 1.57	0.42 Kilograms Interval -0.09 to 0.94
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Hip Abduction-Left - Week 97	-0.11 Kilograms Interval -1.02 to 0.81	-0.07 Kilograms Interval -1.28 to 1.14	0.40 Kilograms Interval -0.25 to 1.05	0.08 Kilograms Interval -0.44 to 0.6
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Hip Abduction-Left - Week 110	-0.18 Kilograms Interval -1.41 to 1.04	-0.68 Kilograms Interval -2.16 to 0.79	0.22 Kilograms Interval -0.92 to 1.36	-0.22 Kilograms Interval -0.93 to 0.48
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Hip Abduction-Left - Week 122	-0.09 Kilograms Interval -2.41 to 2.23	-0.13 Kilograms Interval -1.61 to 1.36	0.58 Kilograms Interval -0.29 to 1.46	0.15 Kilograms Interval -0.65 to 0.95
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Hip Abduction-Left - Week 146	-1.24 Kilograms Interval -4.04 to 1.55	-0.26 Kilograms Interval -2.36 to 1.84	0.84 Kilograms Interval -0.84 to 2.53	-0.22 Kilograms Interval -1.36 to 0.93
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Hip Abduction-Left - Week 170	-4.75 Kilograms Insufficient number of participants to calculate a 95% Confidence Interval.	-2.00 Kilograms Insufficient number of participants to calculate a 95% Confidence Interval.	-0.50 Kilograms Insufficient number of participants to calculate a 95% Confidence Interval.	-2.80 Kilograms Interval -5.16 to -0.44
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Hip Abduction-Right - Baseline	4.14 Kilograms Interval 3.05 to 5.22	5.39 Kilograms Interval 3.95 to 6.83	4.53 Kilograms Interval 3.3 to 5.75	4.69 Kilograms Interval 3.99 to 5.39
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Hip Abduction-Right - Week 9	0.56 Kilograms Interval -0.84 to 1.97	1.05 Kilograms Interval -0.03 to 2.13	0.03 Kilograms Interval -0.61 to 0.67	0.54 Kilograms Interval -0.05 to 1.13
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Hip Abduction-Right - Week 17	0.56 Kilograms Interval -0.62 to 1.75	-0.51 Kilograms Interval -1.67 to 0.66	0.46 Kilograms Interval -0.22 to 1.13	0.18 Kilograms Interval -0.39 to 0.74
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Hip Abduction-Right - Week 25	-0.31 Kilograms Interval -1.44 to 0.83	-0.23 Kilograms Interval -1.57 to 1.11	0.47 Kilograms Interval -0.11 to 1.05	-0.02 Kilograms Interval -0.6 to 0.57
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Hip Abduction-Right - Week 33	0.42 Kilograms Interval -1.09 to 1.93	-0.80 Kilograms Interval -1.89 to 0.29	0.12 Kilograms Interval -0.8 to 1.04	-0.10 Kilograms Interval -0.76 to 0.56
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Hip Abduction-Right - Week 41	-0.18 Kilograms Interval -1.46 to 1.1	-0.60 Kilograms Interval -1.48 to 0.28	0.22 Kilograms Interval -0.6 to 1.03	-0.19 Kilograms Interval -0.74 to 0.35
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Hip Abduction-Right - Week 49	0.92 Kilograms Interval -0.74 to 2.58	-0.67 Kilograms Interval -1.71 to 0.38	0.33 Kilograms Interval -0.38 to 1.03	0.18 Kilograms Interval -0.49 to 0.85
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Hip Abduction-Right - Week 57	0.13 Kilograms Interval -0.91 to 1.16	-0.63 Kilograms Interval -1.66 to 0.41	0.08 Kilograms Interval -0.65 to 0.8	-0.15 Kilograms Interval -0.68 to 0.37
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Hip Abduction-Right - Week 65	0.19 Kilograms Interval -0.82 to 1.2	-0.17 Kilograms Interval -1.52 to 1.18	0.75 Kilograms Interval 0.1 to 1.4	0.25 Kilograms Interval -0.33 to 0.83
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Hip Abduction-Right - Week 73	0.12 Kilograms Interval -0.87 to 1.1	0.04 Kilograms Interval -1.34 to 1.41	0.73 Kilograms Interval 0.03 to 1.42	0.29 Kilograms Interval -0.28 to 0.87
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Hip Abduction-Right - Week 81	0.03 Kilograms Interval -0.97 to 1.02	-0.62 Kilograms Interval -1.62 to 0.38	0.69 Kilograms Interval -0.01 to 1.38	0.04 Kilograms Interval -0.47 to 0.55
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Hip Abduction-Right - Week 89	0.08 Kilograms Interval -0.72 to 0.87	-0.44 Kilograms Interval -1.41 to 0.54	0.68 Kilograms Interval 0.08 to 1.28	0.10 Kilograms Interval -0.36 to 0.56
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Hip Abduction-Right - Week 97	0.05 Kilograms Interval -0.96 to 1.06	-0.20 Kilograms Interval -1.43 to 1.03	0.18 Kilograms Interval -0.93 to 1.29	0.01 Kilograms Interval -0.6 to 0.62
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Hip Abduction-Right - Week 110	0.04 Kilograms Interval -0.96 to 1.05	-1.06 Kilograms Interval -2.77 to 0.66	-0.23 Kilograms Interval -1.79 to 1.33	-0.43 Kilograms Interval -1.23 to 0.37
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Hip Abduction-Right - Week 122	-0.07 Kilograms Interval -2.54 to 2.4	-0.77 Kilograms Interval -2.37 to 0.84	0.52 Kilograms Interval -0.52 to 1.56	-0.09 Kilograms Interval -0.97 to 0.79
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Hip Abduction-Right - Week 146	-1.10 Kilograms Interval -3.32 to 1.12	-1.44 Kilograms Interval -2.89 to 0.01	1.13 Kilograms Interval 0.25 to 2.01	-0.37 Kilograms Interval -1.32 to 0.59
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Shoulder Abduction-Left - Week 9	-0.01 Kilograms Interval -0.78 to 0.76	0.58 Kilograms Interval -0.21 to 1.38	0.08 Kilograms Interval -0.44 to 0.59	0.21 Kilograms Interval -0.17 to 0.6
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Shoulder Abduction-Left - Week 17	0.38 Kilograms Interval -0.41 to 1.16	-0.08 Kilograms Interval -0.84 to 0.68	0.11 Kilograms Interval -0.32 to 0.54	0.13 Kilograms Interval -0.23 to 0.5
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Shoulder Abduction-Left - Week 25	-0.25 Kilograms Interval -0.97 to 0.47	0.08 Kilograms Interval -0.78 to 0.94	0.25 Kilograms Interval -0.15 to 0.64	0.03 Kilograms Interval -0.35 to 0.41
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Shoulder Abduction-Left - Week 33	0.09 Kilograms Interval -1.01 to 1.19	-0.20 Kilograms Interval -0.95 to 0.56	0.12 Kilograms Interval -0.11 to 0.35	0.00 Kilograms Interval -0.42 to 0.42
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Shoulder Abduction-Left - Week 41	0.14 Kilograms Interval -0.94 to 1.23	-0.22 Kilograms Interval -0.9 to 0.46	0.07 Kilograms Interval -0.25 to 0.39	-0.01 Kilograms Interval -0.42 to 0.4
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Shoulder Abduction-Left - Week 49	0.36 Kilograms Interval -0.97 to 1.69	-0.29 Kilograms Interval -0.9 to 0.31	0.19 Kilograms Interval -0.19 to 0.58	0.09 Kilograms Interval -0.39 to 0.56
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Shoulder Abduction-Left - Week 57	-0.05 Kilograms Interval -0.88 to 0.77	-0.49 Kilograms Interval -1.11 to 0.13	0.34 Kilograms Interval -0.06 to 0.73	-0.08 Kilograms Interval -0.44 to 0.28
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Shoulder Abduction-Left - Week 65	-0.20 Kilograms Interval -0.97 to 0.57	0.03 Kilograms Interval -0.96 to 1.02	0.63 Kilograms Interval 0.26 to 0.99	0.15 Kilograms Interval -0.27 to 0.57
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Shoulder Abduction-Left - Week 73	-0.14 Kilograms Interval -0.89 to 0.6	0.13 Kilograms Interval -0.72 to 0.97	0.55 Kilograms Interval 0.19 to 0.9	0.19 Kilograms Interval -0.19 to 0.56
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Shoulder Abduction-Left - Week 81	-0.10 Kilograms Interval -0.77 to 0.57	-0.29 Kilograms Interval -0.98 to 0.4	0.58 Kilograms Interval 0.27 to 0.89	0.07 Kilograms Interval -0.25 to 0.4
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Shoulder Abduction-Left - Week 89	0.02 Kilograms Interval -0.61 to 0.65	-0.32 Kilograms Interval -0.94 to 0.3	0.23 Kilograms Interval -0.12 to 0.57	-0.03 Kilograms Interval -0.33 to 0.27
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Shoulder Abduction-Left - Week 97	0.07 Kilograms Interval -0.64 to 0.78	-0.32 Kilograms Interval -1.08 to 0.44	0.33 Kilograms Interval -0.3 to 0.96	0.03 Kilograms Interval -0.36 to 0.41
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Shoulder Abduction-Left - Week 110	-0.06 Kilograms Interval -0.99 to 0.87	-0.86 Kilograms Interval -2.02 to 0.3	-0.01 Kilograms Interval -0.55 to 0.53	-0.32 Kilograms Interval -0.82 to 0.19
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Shoulder Abduction-Left - Week 122	-0.53 Kilograms Interval -2.12 to 1.07	-0.48 Kilograms Interval -1.38 to 0.42	0.24 Kilograms Interval -0.22 to 0.69	-0.22 Kilograms Interval -0.76 to 0.31
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Shoulder Abduction-Left - Week 146	-0.89 Kilograms Interval -3.08 to 1.31	-0.48 Kilograms Interval -2.23 to 1.27	-0.16 Kilograms Interval -0.64 to 0.33	-0.51 Kilograms Interval -1.28 to 0.26
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Shoulder Abduction-Left - Week 170	-3.75 Kilograms Insufficient number of participants to calculate a 95% Confidence Interval.	-0.90 Kilograms Insufficient number of participants to calculate a 95% Confidence Interval.	0.85 Kilograms Insufficient number of participants to calculate a 95% Confidence Interval.	-1.27 Kilograms Interval -3.62 to 1.09
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Shoulder Abduction-Right - Baseline	3.80 Kilograms Interval 2.81 to 4.79	4.33 Kilograms Interval 3.34 to 5.31	3.46 Kilograms Interval 2.76 to 4.16	3.86 Kilograms Interval 3.37 to 4.36
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Shoulder Abduction-Right - Week 9	-0.19 Kilograms Interval -0.95 to 0.56	0.22 Kilograms Interval -0.5 to 0.95	0.12 Kilograms Interval -0.28 to 0.51	0.05 Kilograms Interval -0.3 to 0.4
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Shoulder Abduction-Right - Week 17	0.06 Kilograms Interval -0.66 to 0.78	-0.16 Kilograms Interval -1.09 to 0.77	0.19 Kilograms Interval -0.15 to 0.54	0.03 Kilograms Interval -0.35 to 0.42
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Shoulder Abduction-Right - Week 25	-0.12 Kilograms Interval -0.94 to 0.71	0.08 Kilograms Interval -1.01 to 1.17	0.49 Kilograms Interval -0.02 to 1.0	0.16 Kilograms Interval -0.31 to 0.62
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Shoulder Abduction-Right - Week 33	-0.16 Kilograms Interval -1.26 to 0.94	-0.54 Kilograms Interval -1.32 to 0.24	0.42 Kilograms Interval 0.11 to 0.73	-0.09 Kilograms Interval -0.53 to 0.35
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Shoulder Abduction-Right - Week 41	-0.20 Kilograms Interval -1.29 to 0.89	-0.47 Kilograms Interval -1.17 to 0.23	0.19 Kilograms Interval -0.09 to 0.47	-0.17 Kilograms Interval -0.58 to 0.25
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Shoulder Abduction-Right - Week 49	0.35 Kilograms Interval -1.48 to 2.18	-0.43 Kilograms Interval -1.02 to 0.16	0.66 Kilograms Interval 0.23 to 1.1	0.18 Kilograms Interval -0.43 to 0.8
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Shoulder Abduction-Right - Week 57	-0.18 Kilograms Interval -1.2 to 0.85	-0.66 Kilograms Interval -1.31 to -0.01	0.33 Kilograms Interval -0.09 to 0.75	-0.19 Kilograms Interval -0.6 to 0.23
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Shoulder Abduction-Right - Week 65	-0.10 Kilograms Interval -1.1 to 0.9	-0.16 Kilograms Interval -0.98 to 0.67	0.25 Kilograms Interval -0.08 to 0.57	-0.01 Kilograms Interval -0.43 to 0.42
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Shoulder Abduction-Right - Week 73	-0.04 Kilograms Interval -1.0 to 0.92	-0.23 Kilograms Interval -0.93 to 0.47	0.58 Kilograms Interval -0.01 to 1.17	0.11 Kilograms Interval -0.32 to 0.53
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Shoulder Abduction-Right - Week 81	0.06 Kilograms Interval -0.93 to 1.06	-0.30 Kilograms Interval -1.01 to 0.41	0.86 Kilograms Interval 0.26 to 1.46	0.22 Kilograms Interval -0.22 to 0.66
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Shoulder Abduction-Right - Week 89	0.10 Kilograms Interval -0.91 to 1.11	-0.52 Kilograms Interval -1.11 to 0.07	0.55 Kilograms Interval 0.1 to 0.99	0.03 Kilograms Interval -0.37 to 0.43
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Shoulder Abduction-Right - Week 97	-0.02 Kilograms Interval -0.96 to 0.92	-0.28 Kilograms Interval -1.08 to 0.53	0.46 Kilograms Interval -0.27 to 1.19	0.06 Kilograms Interval -0.4 to 0.51
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Elbow Extension-Right - Baseline	3.85 Kilograms Interval 2.63 to 5.06	3.49 Kilograms Interval 2.31 to 4.67	2.96 Kilograms Interval 2.25 to 3.66	3.42 Kilograms Interval 2.85 to 4.0
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Elbow Extension-Right - Week 9	-0.43 Kilograms Interval -1.11 to 0.25	0.77 Kilograms Interval -0.28 to 1.82	0.26 Kilograms Interval -0.02 to 0.53	0.20 Kilograms Interval -0.22 to 0.62
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Elbow Extension-Left - Baseline	3.76 Kilograms Interval 2.48 to 5.05	3.51 Kilograms Interval 2.46 to 4.55	2.90 Kilograms Interval 2.25 to 3.55	3.38 Kilograms Interval 2.82 to 3.94
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Elbow Extension-Left - Week 9	-0.10 Kilograms Interval -0.67 to 0.47	0.76 Kilograms Interval -0.09 to 1.61	0.20 Kilograms Interval -0.09 to 0.48	0.29 Kilograms Interval -0.05 to 0.63
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Elbow Extension-Left - Week 17	0.08 Kilograms Interval -0.6 to 0.77	-0.15 Kilograms Interval -1.04 to 0.74	0.17 Kilograms Interval -0.17 to 0.5	0.04 Kilograms Interval -0.33 to 0.4
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Elbow Extension-Left - Week 25	-0.74 Kilograms Interval -1.75 to 0.26	-0.03 Kilograms Interval -1.07 to 1.01	-0.02 Kilograms Interval -0.3 to 0.26	-0.25 Kilograms Interval -0.71 to 0.21
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Elbow Extension-Left - Week 33	-0.65 Kilograms Interval -1.56 to 0.26	-0.37 Kilograms Interval -1.08 to 0.34	0.19 Kilograms Interval -0.23 to 0.62	-0.28 Kilograms Interval -0.67 to 0.12
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Elbow Extension-Left - Week 41	-0.43 Kilograms Interval -1.82 to 0.96	-0.20 Kilograms Interval -1.04 to 0.64	-0.02 Kilograms Interval -0.36 to 0.33	-0.22 Kilograms Interval -0.73 to 0.3
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Elbow Extension-Left - Week 49	-0.65 Kilograms Interval -1.76 to 0.45	-0.46 Kilograms Interval -1.3 to 0.37	0.25 Kilograms Interval -0.14 to 0.65	-0.29 Kilograms Interval -0.75 to 0.17
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Elbow Extension-Left - Week 57	-0.75 Kilograms Interval -1.77 to 0.26	-0.60 Kilograms Interval -1.41 to 0.21	-0.01 Kilograms Interval -0.31 to 0.3	-0.46 Kilograms Interval -0.9 to -0.03
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Elbow Extension-Left - Week 65	-0.70 Kilograms Interval -1.62 to 0.22	-0.30 Kilograms Interval -1.36 to 0.76	0.12 Kilograms Interval -0.25 to 0.48	-0.29 Kilograms Interval -0.76 to 0.17
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Elbow Extension-Left - Week 73	-0.87 Kilograms Interval -1.85 to 0.1	-0.19 Kilograms Interval -1.11 to 0.73	0.27 Kilograms Interval -0.16 to 0.7	-0.24 Kilograms Interval -0.69 to 0.21
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Elbow Extension-Left - Week 81	-0.75 Kilograms Interval -1.65 to 0.15	-0.44 Kilograms Interval -1.21 to 0.33	0.22 Kilograms Interval -0.17 to 0.61	-0.31 Kilograms Interval -0.7 to 0.09
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Elbow Extension-Left - Week 89	-0.63 Kilograms Interval -1.54 to 0.29	-0.69 Kilograms Interval -1.39 to 0.02	0.09 Kilograms Interval -0.36 to 0.54	-0.40 Kilograms Interval -0.79 to -0.01
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Elbow Extension-Left - Week 97	-0.69 Kilograms Interval -1.66 to 0.28	-0.49 Kilograms Interval -1.22 to 0.24	-0.05 Kilograms Interval -0.47 to 0.38	-0.40 Kilograms Interval -0.81 to 0.0
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Elbow Extension-Left - Week 110	-0.99 Kilograms Interval -2.0 to 0.01	-1.08 Kilograms Interval -2.21 to 0.05	-0.36 Kilograms Interval -0.84 to 0.12	-0.81 Kilograms Interval -1.31 to -0.31
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Elbow Extension-Left - Week 122	-1.81 Kilograms Interval -3.3 to -0.32	-0.58 Kilograms Interval -1.56 to 0.4	0.06 Kilograms Interval -0.26 to 0.38	-0.71 Kilograms Interval -1.26 to -0.15
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Elbow Extension-Left - Week 146	-1.90 Kilograms Interval -4.56 to 0.76	-0.72 Kilograms Interval -2.15 to 0.72	0.06 Kilograms Interval -0.43 to 0.54	-0.86 Kilograms Interval -1.79 to 0.07
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Elbow Extension-Left - Week 170	-4.55 Kilograms Insufficient number of participants to calculate a 95% Confidence Interval.	-0.20 Kilograms Insufficient number of participants to calculate a 95% Confidence Interval.	-0.20 Kilograms Insufficient number of participants to calculate a 95% Confidence Interval.	-1.65 Kilograms Interval -4.05 to 0.75
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Elbow Extension-Right - Week 17	0.03 Kilograms Interval -0.88 to 0.93	0.08 Kilograms Interval -1.02 to 1.19	0.30 Kilograms Interval 0.0 to 0.59	0.14 Kilograms Interval -0.31 to 0.59
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Elbow Extension-Right - Week 25	-0.64 Kilograms Interval -1.54 to 0.27	0.13 Kilograms Interval -0.91 to 1.16	0.27 Kilograms Interval 0.03 to 0.51	-0.07 Kilograms Interval -0.52 to 0.38
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Elbow Extension-Right - Week 33	-0.74 Kilograms Interval -1.77 to 0.29	-0.39 Kilograms Interval -1.22 to 0.45	0.20 Kilograms Interval -0.18 to 0.58	-0.30 Kilograms Interval -0.74 to 0.14
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Elbow Extension-Right - Week 41	-0.61 Kilograms Interval -1.74 to 0.52	-0.44 Kilograms Interval -1.22 to 0.35	-0.12 Kilograms Interval -0.47 to 0.24	-0.39 Kilograms Interval -0.84 to 0.06
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Elbow Extension-Right - Week 49	-0.56 Kilograms Interval -1.68 to 0.56	-0.45 Kilograms Interval -1.27 to 0.38	0.04 Kilograms Interval -0.25 to 0.33	-0.32 Kilograms Interval -0.77 to 0.13
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Elbow Extension-Right - Week 57	-1.01 Kilograms Interval -1.98 to -0.04	-0.65 Kilograms Interval -1.5 to 0.21	0.09 Kilograms Interval -0.18 to 0.36	-0.53 Kilograms Interval -0.96 to -0.09
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Elbow Extension-Right - Week 65	-0.88 Kilograms Interval -1.85 to 0.09	-0.20 Kilograms Interval -1.34 to 0.94	0.28 Kilograms Interval -0.14 to 0.71	-0.26 Kilograms Interval -0.77 to 0.24
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Elbow Extension-Right - Week 73	-1.07 Kilograms Interval -2.08 to -0.07	-0.26 Kilograms Interval -1.36 to 0.85	0.17 Kilograms Interval -0.23 to 0.57	-0.37 Kilograms Interval -0.88 to 0.13
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Elbow Flexion-Left - Baseline	4.58 Kilograms Interval 2.96 to 6.19	4.21 Kilograms Interval 3.14 to 5.27	3.83 Kilograms Interval 3.01 to 4.64	4.20 Kilograms Interval 3.54 to 4.85
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Elbow Extension-Right - Week 81	-0.71 Kilograms Interval -1.68 to 0.27	-0.67 Kilograms Interval -1.61 to 0.26	0.59 Kilograms Interval 0.18 to 0.99	-0.25 Kilograms Interval -0.71 to 0.21
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Elbow Extension-Right - Week 89	-1.00 Kilograms Interval -2.08 to 0.08	-0.58 Kilograms Interval -1.4 to 0.24	0.17 Kilograms Interval -0.23 to 0.57	-0.45 Kilograms Interval -0.9 to -0.01
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Elbow Extension-Right - Week 97	-0.76 Kilograms Interval -1.76 to 0.24	-0.48 Kilograms Interval -1.5 to 0.54	-0.04 Kilograms Interval -0.38 to 0.31	-0.42 Kilograms Interval -0.88 to 0.04
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Elbow Extension-Right - Week 110	-1.12 Kilograms Interval -2.21 to -0.03	-0.94 Kilograms Interval -2.1 to 0.23	-0.38 Kilograms Interval -0.92 to 0.17	-0.80 Kilograms Interval -1.33 to -0.28
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Elbow Extension-Right - Week 122	-1.77 Kilograms Interval -3.53 to -0.01	-0.63 Kilograms Interval -1.25 to -0.02	0.14 Kilograms Interval -0.34 to 0.61	-0.65 Kilograms Interval -1.21 to -0.09
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Elbow Extension-Right - Week 146	-1.70 Kilograms Interval -4.42 to 1.02	-0.75 Kilograms Interval -1.06 to -0.44	-0.03 Kilograms Interval -0.74 to 0.68	-0.83 Kilograms Interval -1.7 to 0.04
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Elbow Extension-Right - Week 170	-4.35 Kilograms Insufficient number of participants to calculate a 95% Confidence Interval.	-1.45 Kilograms Insufficient number of participants to calculate a 95% Confidence Interval.	-0.15 Kilograms Insufficient number of participants to calculate a 95% Confidence Interval.	-1.98 Kilograms Interval -4.01 to 0.04
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Elbow Flexion-Left -Week 17	-0.37 Kilograms Interval -1.69 to 0.95	-0.05 Kilograms Interval -0.82 to 0.72	-0.05 Kilograms Interval -0.56 to 0.47	-0.15 Kilograms Interval -0.65 to 0.35
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Elbow Flexion-Left - Week 25	-0.72 Kilograms Interval -2.29 to 0.85	0.02 Kilograms Interval -1.05 to 1.09	-0.06 Kilograms Interval -0.48 to 0.37	-0.24 Kilograms Interval -0.83 to 0.36
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Elbow Flexion-Left - Week 33	-0.59 Kilograms Interval -1.97 to 0.79	-0.45 Kilograms Interval -1.1 to 0.2	-0.04 Kilograms Interval -0.41 to 0.34	-0.36 Kilograms Interval -0.85 to 0.13
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Elbow Flexion-Left - Week 41	-0.77 Kilograms Interval -2.4 to 0.87	-0.41 Kilograms Interval -1.11 to 0.29	-0.34 Kilograms Interval -0.75 to 0.06	-0.50 Kilograms Interval -1.06 to 0.06
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Elbow Flexion-Left - Week 49	-1.12 Kilograms Interval -2.41 to 0.18	-0.66 Kilograms Interval -1.36 to 0.04	-0.18 Kilograms Interval -0.76 to 0.4	-0.65 Kilograms Interval -1.16 to -0.15
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Elbow Flexion-Left - Week 57	-1.02 Kilograms Interval -2.43 to 0.39	-0.57 Kilograms Interval -1.27 to 0.14	-0.29 Kilograms Interval -0.75 to 0.16	-0.63 Kilograms Interval -1.15 to -0.11
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Elbow Flexion-Left - Week 65	-1.01 Kilograms Interval -2.39 to 0.38	-0.67 Kilograms Interval -1.52 to 0.18	-0.20 Kilograms Interval -0.6 to 0.2	-0.63 Kilograms Interval -1.15 to -0.1
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Elbow Flexion-Left - Week 73	-1.10 Kilograms Interval -2.44 to 0.24	-0.36 Kilograms Interval -1.22 to 0.51	-0.24 Kilograms Interval -0.95 to 0.47	-0.55 Kilograms Interval -1.08 to -0.01
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Elbow Flexion-Left - Week 81	-0.91 Kilograms Interval -2.28 to 0.46	-0.62 Kilograms Interval -1.37 to 0.13	-0.19 Kilograms Interval -0.65 to 0.28	-0.56 Kilograms Interval -1.06 to -0.06
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Elbow Flexion-Left - Week 89	-0.84 Kilograms Interval -2.19 to 0.51	-0.84 Kilograms Interval -1.58 to -0.11	-0.35 Kilograms Interval -0.85 to 0.15	-0.67 Kilograms Interval -1.14 to -0.19
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Elbow Flexion-Left - Week 97	-0.71 Kilograms Interval -2.24 to 0.82	-0.68 Kilograms Interval -1.56 to 0.2	-0.55 Kilograms Interval -1.2 to 0.11	-0.64 Kilograms Interval -1.22 to -0.06
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Elbow Flexion-Left - Week 110	-1.28 Kilograms Interval -2.94 to 0.38	-1.01 Kilograms Interval -2.13 to 0.11	-1.05 Kilograms Interval -1.77 to -0.34	-1.11 Kilograms Interval -1.76 to -0.47
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Elbow Flexion-Left - Week 122	-2.32 Kilograms Interval -4.57 to -0.06	-0.95 Kilograms Interval -2.06 to 0.16	-0.61 Kilograms Interval -1.13 to -0.08	-1.23 Kilograms Interval -1.97 to -0.49
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Elbow Flexion-Left - Week 146	-1.94 Kilograms Interval -4.63 to 0.75	-0.42 Kilograms Interval -2.43 to 1.6	-0.53 Kilograms Interval -1.46 to 0.41	-0.99 Kilograms Interval -1.98 to 0.0
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Elbow Flexion-Left - Week 170	-4.70 Kilograms Insufficient number of participants to calculate a 95% Confidence Interval.	-1.25 Kilograms Insufficient number of participants to calculate a 95% Confidence Interval.	-1.25 Kilograms Insufficient number of participants to calculate a 95% Confidence Interval.	-2.40 Kilograms Interval -4.3 to -0.5
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Elbow Flexion-Right - Baseline	4.66 Kilograms Interval 3.43 to 5.89	4.24 Kilograms Interval 3.18 to 5.3	3.73 Kilograms Interval 2.93 to 4.53	4.20 Kilograms Interval 3.63 to 4.77
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Elbow Flexion-Right - Week 9	-0.47 Kilograms Interval -1.39 to 0.45	0.65 Kilograms Interval -0.19 to 1.48	0.49 Kilograms Interval -0.02 to 1.0	0.23 Kilograms Interval -0.21 to 0.66
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Elbow Flexion-Right - Week 17	0.09 Kilograms Interval -0.83 to 1.02	-0.08 Kilograms Interval -0.97 to 0.8	0.11 Kilograms Interval -0.23 to 0.45	0.04 Kilograms Interval -0.37 to 0.45
Change From Baseline on the Myometry Based Muscle Strength - Overall Baseline Elbow Flexion-Right - Week 25	-0.67 Kilograms Interval -1.58 to 0.24	-0.14 Kilograms Interval -1.2 to 0.92	0.00 Kilograms Interval -0.44 to 0.44	-0.26 Kilograms Interval -0.73 to 0.2

SECONDARY outcome

Timeframe: Weeks 1, 25, 49 and 73

Population: The analysis population included all participants who had received at least 1 dose of study medication and had at least 1 PF-06252616 concentration measured in study B5161004. Participants without contributing to the summary statistics are excluded below. Number analyzed refers to number of participants evaluable for specified rows of time points.

Outcome measures

Outcome measures
Measure	Sequence 1 n=14 Participants In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 2 n=17 Participants In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 3 n=14 Participants In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Total Sum of all participants in the study B5161004
Serum PF-06252616 (Domagrozumab) Concentration Versus Time Summary Week 1	145774.93 Nanogram Per Milliliter (ng/mL) Standard Deviation 56594.3925	33.3529 Nanogram Per Milliliter (ng/mL) Standard Deviation 137.5176	238433.36 Nanogram Per Milliliter (ng/mL) Standard Deviation 119862.330	—
Serum PF-06252616 (Domagrozumab) Concentration Versus Time Summary Week 25	355111.67 Nanogram Per Milliliter (ng/mL) Standard Deviation 90842.1052	345943.67 Nanogram Per Milliliter (ng/mL) Standard Deviation 73922.3955	488082.31 Nanogram Per Milliliter (ng/mL) Standard Deviation 199634.909	—
Serum PF-06252616 (Domagrozumab) Concentration Versus Time Summary Week 49	405812.43 Nanogram Per Milliliter (ng/mL) Standard Deviation 110320.246	379259.33 Nanogram Per Milliliter (ng/mL) Standard Deviation 71128.3552	459825.13 Nanogram Per Milliliter (ng/mL) Standard Deviation 49395.4262	—
Serum PF-06252616 (Domagrozumab) Concentration Versus Time Summary Week 73	401899.50 Nanogram Per Milliliter (ng/mL) Standard Deviation 3068.1363	400176.00 Nanogram Per Milliliter (ng/mL) Standard Deviation 84223.4887	401847.50 Nanogram Per Milliliter (ng/mL) Standard Deviation 164854.168	—

SECONDARY outcome

Timeframe: Weeks 1, 25, 49, 73 and Early Termination

Population: The analysis population included all participants who had received at least 1 dose of study medication in current study B5161004. 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. The criterion for negative result of ADA samples was ADA titer \<1.88.

Outcome measures

Outcome measures
Measure	Sequence 1 n=19 Participants In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 2 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 3 n=20 Participants In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Total n=59 Participants Sum of all participants in the study B5161004
Number of Participants With Anti-drug Antibodies (ADA) Development Week 1- Positive >=1.88	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Anti-drug Antibodies (ADA) Development Week 1 - Negative <1.88	14 Participants	17 Participants	14 Participants	45 Participants
Number of Participants With Anti-drug Antibodies (ADA) Development Week 25 - Positive >=1.88	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Anti-drug Antibodies (ADA) Development Week 25 -Negative <1.88	12 Participants	12 Participants	13 Participants	37 Participants
Number of Participants With Anti-drug Antibodies (ADA) Development Week 49 - Positive >= 1.88	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Anti-drug Antibodies (ADA) Development Week 49 -Negative <1.88	7 Participants	6 Participants	8 Participants	21 Participants
Number of Participants With Anti-drug Antibodies (ADA) Development Week 73 - Positive >=1.88	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Anti-drug Antibodies (ADA) Development Week 73 -Negative <1.88	2 Participants	2 Participants	2 Participants	6 Participants
Number of Participants With Anti-drug Antibodies (ADA) Development Early Termination-Positive>=1.88	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Anti-drug Antibodies (ADA) Development Early Termination-Negative<1.88	16 Participants	14 Participants	13 Participants	43 Participants

Adverse Events

Sequence 1

Serious events: 2 serious events

Other events: 15 other events

Deaths: 0 deaths

Sequence 2

Serious events: 2 serious events

Other events: 17 other events

Deaths: 0 deaths

Sequence 3

Serious events: 1 serious events

Other events: 17 other events

Deaths: 0 deaths

Total

Serious events: 5 serious events

Other events: 49 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Sequence 1 n=19 participants at risk In study B5161002 (parent study) participants randomized to Sequence group 1 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by intravenous (IV) infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received domagrozumab every 4 weeks for a total of 48 weeks at 40 mg/kg, the maximum tolerated dose identified in Period 1. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 2 n=20 participants at risk In study B5161002 (parent study) participants randomized to Sequence group 2 received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg) in Period 1. At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. In Period 2, participants received placebo. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Sequence 3 n=20 participants at risk In study B5161002 (parent study) participants randomized to Sequence group 3 received placebo in Period 1 (48 weeks). In Period 2, participants received domagrozumab (PF-06252616) in a dose escalating fashion (5, 20 and 40 mg/kg). At each dose level, domagrozumab was administered over 2 hours by IV infusion every 4 weeks for a total of 16 weeks. There was no pause between Period 1 and Period 2 (48 weeks each). In study B5161004 (OLE) participants received domagrozumab 40 mg/kg (the maximum tolerated dose from B5161002) every 4 weeks until early termination of this study. The OLE study reports participants within the treatment assignment they received in the parent study.	Total n=59 participants at risk Sum of all participants in the study B5161004
Cardiac disorders Fat embolism syndrome	0.00% 0/19 • 2 Years The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a 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% 0/20 • 2 Years The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a 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% 1/20 • Number of events 1 • 2 Years The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	1.7% 1/59 • Number of events 1 • 2 Years The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a 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 Ileus paralytic	0.00% 0/19 • 2 Years The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a 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% 1/20 • Number of events 3 • 2 Years The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a 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% 0/20 • 2 Years The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	1.7% 1/59 • Number of events 3 • 2 Years The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Cardiac disorders Angina pectoris	5.3% 1/19 • Number of events 1 • 2 Years The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a 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% 0/20 • 2 Years The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a 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% 0/20 • 2 Years The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	1.7% 1/59 • Number of events 1 • 2 Years The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a 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 Volvulus	0.00% 0/19 • 2 Years The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a 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% 1/20 • Number of events 1 • 2 Years The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a 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% 0/20 • 2 Years The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	1.7% 1/59 • Number of events 1 • 2 Years The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a 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 Appendicitis	5.3% 1/19 • Number of events 1 • 2 Years The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a 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% 0/20 • 2 Years The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a 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% 0/20 • 2 Years The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	1.7% 1/59 • Number of events 1 • 2 Years The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a 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	5.3% 1/19 • Number of events 1 • 2 Years The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a 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% 0/20 • 2 Years The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a 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% 0/20 • 2 Years The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	1.7% 1/59 • Number of events 1 • 2 Years The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a 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 Seizure	0.00% 0/19 • 2 Years The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a 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% 1/20 • Number of events 1 • 2 Years The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a 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% 0/20 • 2 Years The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.	1.7% 1/59 • Number of events 1 • 2 Years The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a 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

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