Trial Outcomes & Findings for A Study to Evaluate the Efficacy and Safety of Pegcetacoplan in Patients With Cold Agglutinin Disease (CAD) (NCT NCT05096403)

Last Updated: 2025-10-30

Results Overview

A participant was considered to have a response if the Hgb level increased greater than or equal to (\>=) 1.5 gram per deciliter (g/dL) from baseline and this increase was maintained from Week 16 through Week 24 in absence of blood transfusion from Week 5 through Week 24.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

24 participants

Primary outcome timeframe

Week 24

Results posted on

2025-10-30

Participant Flow

Participant milestones

Participant milestones
Measure	Pegcetacoplan Double Blind During Part A 1080 mg, subcutaneous injection, twice weekly Pegcetacoplan: Pegcetacoplan taken twice weekly as subcutaneous injection	Placebo Matching Pegcetacoplan-Double-blind During Part A Sodium acetate, subcutaneous injection, twice weekly Placebo matching pegcetacoplan taken twice weekly as subcutaneous injection
Double-blind (Part A) STARTED	16	8
Double-blind (Part A) COMPLETED	14	7
Double-blind (Part A) NOT COMPLETED	2	1
Open-label treatment (Part B) STARTED	14	7
Open-label treatment (Part B) COMPLETED	8	3
Open-label treatment (Part B) NOT COMPLETED	6	4
Open-label maintenance period (Part C) STARTED	8	3
Open-label maintenance period (Part C) COMPLETED	0	0
Open-label maintenance period (Part C) NOT COMPLETED	8	3

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study to Evaluate the Efficacy and Safety of Pegcetacoplan in Patients With Cold Agglutinin Disease (CAD)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pegcetacoplan Double Blind During Part A n=16 Participants 1080 mg, subcutaneous injection, twice weekly Pegcetacoplan: Pegcetacoplan taken twice weekly as subcutaneous injection	Placebo Matching Pegcetacoplan-Double-blind During Part A n=8 Participants Placebo matching pegcetacoplan taken twice weekly as subcutaneous injection	Total n=24 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Age, Categorical >=65 years	13 Participants n=5 Participants	7 Participants n=7 Participants	20 Participants n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	6 Participants n=7 Participants	12 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants	2 Participants n=7 Participants	12 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	4 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	12 Participants n=5 Participants	8 Participants n=7 Participants	20 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Disease History-Time since diagnosis	6.0 Years STANDARD_DEVIATION 5.09 • n=5 Participants	7.0 Years STANDARD_DEVIATION 8.60 • n=7 Participants	6.3 Years STANDARD_DEVIATION 6.30 • n=5 Participants

PRIMARY outcome

Timeframe: Week 24

Outcome measures

Outcome measures
Measure	Pegcetacoplan Double Blind During Part A n=16 Participants 1080 mg, subcutaneous injection, twice weekly	Placebo Matching Pegcetacoplan-Double-blind During Part A n=8 Participants Placebo matching pegcetacoplan taken twice weekly as subcutaneous injection
Number of Patients Achieving a Response (R) at Week 24	8 Participants	2 Participants

SECONDARY outcome

Timeframe: Week 24

Outcome measures

Outcome measures
Measure	Pegcetacoplan Double Blind During Part A n=16 Participants 1080 mg, subcutaneous injection, twice weekly	Placebo Matching Pegcetacoplan-Double-blind During Part A n=8 Participants Placebo matching pegcetacoplan taken twice weekly as subcutaneous injection
Change From Baseline to Week 24 in Hemoglobin (Hgb) Level-Part A in the Absence of Intercurrent Events (ICEs).	2.85 grams per deciliter (g/dL) Standard Error 0.306	1.36 grams per deciliter (g/dL) Standard Error 0.278

SECONDARY outcome

Timeframe: Week 24

Population: Number of Patients Achieving Transfusion Avoidance at Week 24

Percentage of patients who did not receive a blood transfusion between Week 5 and Week 24 was assessed

Outcome measures

Outcome measures
Measure	Pegcetacoplan Double Blind During Part A n=16 Participants 1080 mg, subcutaneous injection, twice weekly	Placebo Matching Pegcetacoplan-Double-blind During Part A n=8 Participants Placebo matching pegcetacoplan taken twice weekly as subcutaneous injection
Number of Patients Achieving Transfusion Avoidance From Week 5 to Week 24-Part A	12 Participants Interval -0.374 to 0.691	5 Participants Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: Week 24

Population: Part A

The ICEs of interest were : * Withdrawal from treatment or lost to follow-up before the end of the double-blind period * Use of prohibited medications (rituximab alone or in combination, any other complement inhibitor, any other investigational drug, and plasma exchange). FACT-An is used to measure quality of life (QoL) in patients with anemia. Each item is rated on a 5-point Likert scale:0=Not at all, 1=A little bit ,2=Somewhat, 3=Quite a bit, 4=Very much. Some items are reverse scored. Higher scores in this scale denote a better QoL with less impact of anemia.The total FACT-An scale score ranges from 0 to 160. The total score gives a comprehensive view of a patient's well-being. It combines the FACT-G with an Anemia subscale. FACT-G (27 items):Physical Well-Being (PWB) and Social/Family Well-Being (SWB) 14 items in total, Emotional Well-Being (EWB)-6 items,Functional Well-Being (FWB)-7 items, Anemia Subscale (AnS): 13 items. Total FACT-An score=FACT-G + Anemia Subscale=40 item

Outcome measures

Outcome measures
Measure	Pegcetacoplan Double Blind During Part A n=16 Participants 1080 mg, subcutaneous injection, twice weekly	Placebo Matching Pegcetacoplan-Double-blind During Part A n=8 Participants Placebo matching pegcetacoplan taken twice weekly as subcutaneous injection
Change From Baseline to Week 24 in FACT-An Scale Score (Quality of Life)-Part A in the Absence of Intercurrent Events (ICEs)	20.67 Units on a scale Standard Deviation 19.175	16.40 Units on a scale Standard Deviation 37.246

SECONDARY outcome

Timeframe: Week 24

Number of blood transfusions received between Week 5 and Week 24 were assessed.

Outcome measures

Outcome measures
Measure	Pegcetacoplan Double Blind During Part A n=16 Participants 1080 mg, subcutaneous injection, twice weekly	Placebo Matching Pegcetacoplan-Double-blind During Part A n=8 Participants Placebo matching pegcetacoplan taken twice weekly as subcutaneous injection
Number of Packed Red Blood Cell Transfusions Received by Patients From Week 5 to Week 24-Part A	1.5 Number of transfusions Standard Deviation 3.62	1.1 Number of transfusions Standard Deviation 2.80

SECONDARY outcome

Timeframe: Week 24

Outcome measures

Outcome measures
Measure	Pegcetacoplan Double Blind During Part A n=16 Participants 1080 mg, subcutaneous injection, twice weekly	Placebo Matching Pegcetacoplan-Double-blind During Part A n=8 Participants Placebo matching pegcetacoplan taken twice weekly as subcutaneous injection
Change From Baseline to Week 24 in LDH Levels-Part A in the Absence of Intercurrent Events (ICEs)	-251.73 U/L Standard Deviation 211.312	-82.00 U/L Standard Deviation 138.477

SECONDARY outcome

Timeframe: Week 24

Outcome measures

Outcome measures
Measure	Pegcetacoplan Double Blind During Part A n=16 Participants 1080 mg, subcutaneous injection, twice weekly	Placebo Matching Pegcetacoplan-Double-blind During Part A n=8 Participants Placebo matching pegcetacoplan taken twice weekly as subcutaneous injection
Change From Baseline to Week 24 in Haptoglobin Levels-Part A in the Absence of Intercurrent Events (ICEs)	0.31 g/L Standard Deviation 0.493	0.01 g/L Standard Deviation 0.020

SECONDARY outcome

Timeframe: Week 24

Outcome measures

Outcome measures
Measure	Pegcetacoplan Double Blind During Part A n=16 Participants 1080 mg, subcutaneous injection, twice weekly	Placebo Matching Pegcetacoplan-Double-blind During Part A n=8 Participants Placebo matching pegcetacoplan taken twice weekly as subcutaneous injection
Change From Baseline to Week 24 in Indirect Bilirubin-Part A in the Absence of Intercurrent Events (ICE)	-31.55 µmol/L Standard Deviation 23.340	8.20 µmol/L Standard Deviation 19.325

SECONDARY outcome

Timeframe: Week 24

Outcome measures

Outcome measures
Measure	Pegcetacoplan Double Blind During Part A n=16 Participants 1080 mg, subcutaneous injection, twice weekly	Placebo Matching Pegcetacoplan-Double-blind During Part A n=8 Participants Placebo matching pegcetacoplan taken twice weekly as subcutaneous injection
Change From Baseline to Week 24 in ARC-Part A in the Absence of Intercurrent Events (ICEs)	-41.17 10^9 cells/L Standard Deviation 62.438	-37.96 10^9 cells/L Standard Deviation 19.891

SECONDARY outcome

Timeframe: Week 24

* Withdrawal from treatment or lost to follow-up before the end of the double-blind period * Use of prohibited medications (rituximab alone or in combination, any other complement inhibitor, any other investigational drug, and plasma exchange) change from baseline to Week 24 in D-dimer levels.

Outcome measures

Outcome measures
Measure	Pegcetacoplan Double Blind During Part A n=16 Participants 1080 mg, subcutaneous injection, twice weekly	Placebo Matching Pegcetacoplan-Double-blind During Part A n=8 Participants Placebo matching pegcetacoplan taken twice weekly as subcutaneous injection
Change From Baseline to Week 24 in D-dimer Levels-Part A in the Absence of Intercurrent Events (ICEs	-698.70 µg/L FEU Standard Deviation 927.480	-1722.75 µg/L FEU Standard Deviation 3089.162

SECONDARY outcome

Timeframe: Week 24

Percentage of patients with LDH level within normal ranges and with an abnormal value at baseline.

Outcome measures

Outcome measures
Measure	Pegcetacoplan Double Blind During Part A n=13 Participants 1080 mg, subcutaneous injection, twice weekly	Placebo Matching Pegcetacoplan-Double-blind During Part A n=8 Participants Placebo matching pegcetacoplan taken twice weekly as subcutaneous injection
Normalization of Markers of Hemolysis (LDH) at Week 24-Part A	5 Participants	1 Participants

SECONDARY outcome

Timeframe: Week 24

Percentage of patients with Indirect Bilirubin level within normal ranges and with an abnormal value at baseline.

Outcome measures

Outcome measures
Measure	Pegcetacoplan Double Blind During Part A n=13 Participants 1080 mg, subcutaneous injection, twice weekly	Placebo Matching Pegcetacoplan-Double-blind During Part A n=6 Participants Placebo matching pegcetacoplan taken twice weekly as subcutaneous injection
Normalization of Markers of Hemolysis (Indirect Bilirubin) at Week 24-Part A	9 Participants	1 Participants

SECONDARY outcome

Timeframe: Week 24

Percentage of patients with ARC level within normal ranges and with an abnormal value at baseline.

Outcome measures

Outcome measures
Measure	Pegcetacoplan Double Blind During Part A n=10 Participants 1080 mg, subcutaneous injection, twice weekly	Placebo Matching Pegcetacoplan-Double-blind During Part A n=8 Participants Placebo matching pegcetacoplan taken twice weekly as subcutaneous injection
Normalization of Markers of Hemolysis (ARC) at Week 24-Part A	4 Participants	2 Participants

SECONDARY outcome

Timeframe: Week 24

Percentage of patients with haptoglobin level within normal ranges and with an abnormal value at baseline.

Outcome measures

Outcome measures
Measure	Pegcetacoplan Double Blind During Part A n=15 Participants 1080 mg, subcutaneous injection, twice weekly	Placebo Matching Pegcetacoplan-Double-blind During Part A n=6 Participants Placebo matching pegcetacoplan taken twice weekly as subcutaneous injection
Normalization of Markers of Hemolysis (Haptoglobin) at Week 24-Part A	4 Participants	0 Participants

SECONDARY outcome

Timeframe: Week 24

Percentage of patients with haptoglobin level normalization during the initial 24 weeks of the study

Outcome measures

Outcome measures
Measure	Pegcetacoplan Double Blind During Part A n=15 Participants 1080 mg, subcutaneous injection, twice weekly	Placebo Matching Pegcetacoplan-Double-blind During Part A n=6 Participants Placebo matching pegcetacoplan taken twice weekly as subcutaneous injection
Count and Percentage of Patients With a First Normalization From Baseline by Week 24 for Haptoglobin Levels-Part A	7 Participants	0 Participants

SECONDARY outcome

Timeframe: Week 24

Percentage of patients with Hemoglobin level normalization during the initial 24 weeks of the study

Outcome measures

Outcome measures
Measure	Pegcetacoplan Double Blind During Part A n=16 Participants 1080 mg, subcutaneous injection, twice weekly	Placebo Matching Pegcetacoplan-Double-blind During Part A n=8 Participants Placebo matching pegcetacoplan taken twice weekly as subcutaneous injection
Count and Percentage of Patients With a First Normalization From Baseline by Week 24 for Hemoglobin Levels-Part A	7 Participants	0 Participants

SECONDARY outcome

Timeframe: Week 24

Percentage of patients with LDH level normalization during the initial 24 weeks of the study

Outcome measures

Outcome measures
Measure	Pegcetacoplan Double Blind During Part A n=13 Participants 1080 mg, subcutaneous injection, twice weekly	Placebo Matching Pegcetacoplan-Double-blind During Part A n=8 Participants Placebo matching pegcetacoplan taken twice weekly as subcutaneous injection
Count and Percentage of Patients With a First Normalization From Baseline by Week 24 for LDH Levels-Part A	6 Participants	2 Participants

SECONDARY outcome

Timeframe: Week 24

Percentage of patients with Indirect Bilirubin level normalization during the initial 24 weeks of the study

Outcome measures

Outcome measures
Measure	Pegcetacoplan Double Blind During Part A n=13 Participants 1080 mg, subcutaneous injection, twice weekly	Placebo Matching Pegcetacoplan-Double-blind During Part A n=6 Participants Placebo matching pegcetacoplan taken twice weekly as subcutaneous injection
Count and Percentage of Patients With a First Normalization From Baseline by Week 24 for Indirect Bilirubin Levels-Part A	11 Participants	1 Participants

SECONDARY outcome

Timeframe: Week 24

Percentage of patients with ARC level normalization during the initial 24 weeks of the study

Outcome measures

Outcome measures
Measure	Pegcetacoplan Double Blind During Part A n=10 Participants 1080 mg, subcutaneous injection, twice weekly	Placebo Matching Pegcetacoplan-Double-blind During Part A n=8 Participants Placebo matching pegcetacoplan taken twice weekly as subcutaneous injection
Count and Percentage of Patients With a First Normalization From Baseline by Week 24 for ARC Levels-Part A	9 Participants	3 Participants

SECONDARY outcome

Timeframe: Week 5 to Week 24

Number of PRBC units transfused from Week 5 and Week 24 was assessed

Outcome measures

Outcome measures
Measure	Pegcetacoplan Double Blind During Part A n=16 Participants 1080 mg, subcutaneous injection, twice weekly	Placebo Matching Pegcetacoplan-Double-blind During Part A n=8 Participants Placebo matching pegcetacoplan taken twice weekly as subcutaneous injection
Number of Packed Red Blood Cell Units Transfused From Week 5 to Week 24-Part A	2.47 Number of PRBC units transfused Standard Deviation 5.944	1.88 Number of PRBC units transfused Standard Deviation 4.549

SECONDARY outcome

Timeframe: Week 24

Population: Part A

The ICEs of interest were : * Withdrawal from treatment or lost to follow-up before the end of the double-blind period * Use of prohibited medications (rituximab alone or in combination, any other complement inhibitor, any other investigational drug, and plasma exchange). The FACIT-F subscale is used to measure fatigue and its impact upon daily activities and function in patients with chronic illnesses and contains 20 items related to the impact of fatigue. Each item is scored on a 0-4 scale, with some items reverse-scored. Total scores range from 0 to 52, where higher scores indicate less fatigue and better outcomes, and lower scores reflect greater fatigue. It can be used alone or with other FACIT subscales as part of broader quality of life assessments.

Outcome measures

Outcome measures
Measure	Pegcetacoplan Double Blind During Part A n=16 Participants 1080 mg, subcutaneous injection, twice weekly	Placebo Matching Pegcetacoplan-Double-blind During Part A n=8 Participants Placebo matching pegcetacoplan taken twice weekly as subcutaneous injection
Change From Baseline to Week 24 in FACIT-F Subscale Score-Part A in the Absence of Intercurrent Events (ICEs)	9.73 Units on a scale Standard Deviation 11.028	8.80 Units on a scale Standard Deviation 18.130

SECONDARY outcome

Timeframe: Week 24

The ICEs of interest were : * Withdrawal from treatment or lost to follow-up before the end of the double-blind period * Use of prohibited medications (rituximab alone or in combination, any other complement inhibitor, any other investigational drug, and plasma exchange. SF-12 is a 12-item health survey assessing physical and mental health. Higher scores mean better health with scores above 50 indicating better than average health. It produces two summary scores: the Physical Component Summary (PCS) and Mental Component Summary (MCS), both norm-based (mean=50, SD=10), with ranges of \~5-80 (PCS) and \~-3.3-80 (MCS). Higher scores=better health. It also covers 8 subscales-Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH), each scored between 0-100, where higher=better functioning. Scores are computed using weighted formulas from item responses (not simple averages).

Outcome measures

Outcome measures
Measure	Pegcetacoplan Double Blind During Part A n=16 Participants 1080 mg, subcutaneous injection, twice weekly	Placebo Matching Pegcetacoplan-Double-blind During Part A n=8 Participants Placebo matching pegcetacoplan taken twice weekly as subcutaneous injection
Change From Baseline to Week 24 in SF-12-Part A in the Absence of Intercurrent Events (ICEs) Physical Component Score at Week 24	4.95 units on a scale Standard Deviation 7.965	4.46 units on a scale Standard Deviation 11.867
Change From Baseline to Week 24 in SF-12-Part A in the Absence of Intercurrent Events (ICEs) Mental Component Score at Week 24	5.53 units on a scale Standard Deviation 9.935	2.50 units on a scale Standard Deviation 9.777

SECONDARY outcome

Timeframe: Week 24

The EQ-5D-5L measures total health across 5 dimensions: Mobility, Self-care, Usual Activities, Pain/Discomfort, and Anxiety/Depression-each scored from 1 (no problems) to 5 (extreme problems). Scores form a 5-digit health profile (e.g., 12345). Each individual score plus a VAS for perceived health status today are separately reported. Higher scores reflect better total health. The EQ VAS is a patient-rated score from 0 (worst) to 100 (best health). The ICEs of interest were : * Withdrawal from treatment or lost to follow-up before the end of the of the double-blind period * Use of prohibited medications (rituximab alone or in combination, any other complement inhibitor, any other investigational drug, and plasma exchange).

Outcome measures

Outcome measures
Measure	Pegcetacoplan Double Blind During Part A n=16 Participants 1080 mg, subcutaneous injection, twice weekly	Placebo Matching Pegcetacoplan-Double-blind During Part A n=8 Participants Placebo matching pegcetacoplan taken twice weekly as subcutaneous injection
Change From Baseline to Week 24 in EQ-5D-5L Questionnaire -Part A in the Absence of Intercurrent Events (ICEs) Mobility-Part A	0.50 units on a scale Standard Deviation 1.087	0.00 units on a scale Standard Deviation 1.633
Change From Baseline to Week 24 in EQ-5D-5L Questionnaire -Part A in the Absence of Intercurrent Events (ICEs) Self-care-Part A	0.00 units on a scale Standard Deviation 0.447	1.00 units on a scale Standard Deviation 1.414
Change From Baseline to Week 24 in EQ-5D-5L Questionnaire -Part A in the Absence of Intercurrent Events (ICEs) Usual activities-Part A	0.58 units on a scale Standard Deviation 0.669	0.00 units on a scale Standard Deviation 0.816
Change From Baseline to Week 24 in EQ-5D-5L Questionnaire -Part A in the Absence of Intercurrent Events (ICEs) Pain/Discomfort-Part A	0.25 units on a scale Standard Deviation 0.866	-0.75 units on a scale Standard Deviation 1.258
Change From Baseline to Week 24 in EQ-5D-5L Questionnaire -Part A in the Absence of Intercurrent Events (ICEs) Anxiety/Depression-Part A	0.33 units on a scale Standard Deviation 0.492	0.00 units on a scale Standard Deviation 0.816

SECONDARY outcome

Timeframe: Week 48

Population: Part B

Outcome measures

Outcome measures
Measure	Pegcetacoplan Double Blind During Part A n=14 Participants 1080 mg, subcutaneous injection, twice weekly	Placebo Matching Pegcetacoplan-Double-blind During Part A n=7 Participants Placebo matching pegcetacoplan taken twice weekly as subcutaneous injection
Change From Baseline to Week 48 in Hemoglobin (Hgb) Level-Part B in the Absence of Intercurrent Events (ICEs).	3.00 grams per deciliter (g/dL) Standard Deviation 2.101	3.35 grams per deciliter (g/dL) Standard Deviation 0.995

SECONDARY outcome

Timeframe: Week 48

Population: Part B

Outcome measures

Outcome measures
Measure	Pegcetacoplan Double Blind During Part A n=14 Participants 1080 mg, subcutaneous injection, twice weekly	Placebo Matching Pegcetacoplan-Double-blind During Part A n=7 Participants Placebo matching pegcetacoplan taken twice weekly as subcutaneous injection
Change From Baseline to Week 48 in LDH Level-Part B in the Absence of Intercurrent Events (ICEs).	-220.25 U/L Standard Deviation 168.347	-259.25 U/L Standard Deviation 52.258

SECONDARY outcome

Timeframe: Week 48

Population: Part B

Outcome measures

Outcome measures
Measure	Pegcetacoplan Double Blind During Part A n=14 Participants 1080 mg, subcutaneous injection, twice weekly	Placebo Matching Pegcetacoplan-Double-blind During Part A n=7 Participants Placebo matching pegcetacoplan taken twice weekly as subcutaneous injection
Change From Baseline to Week 48 in Haptoglobin Level-Part B in the Absence of Intercurrent Events (ICEs).	0.18 grams per deciliter (g/dL) Standard Deviation 0.238	0.69 grams per deciliter (g/dL) Standard Deviation 0.262

SECONDARY outcome

Timeframe: Week 48

Population: Part B

Outcome measures

Outcome measures
Measure	Pegcetacoplan Double Blind During Part A n=14 Participants 1080 mg, subcutaneous injection, twice weekly	Placebo Matching Pegcetacoplan-Double-blind During Part A n=7 Participants Placebo matching pegcetacoplan taken twice weekly as subcutaneous injection
Change From Baseline to Week 48 in Indirect Bilirubin Level-Part B in the Absence of Intercurrent Events (ICEs).	-40.19 µmol/L Standard Deviation 28.546	-33.43 µmol/L Standard Deviation 25.237

SECONDARY outcome

Timeframe: Week 48

Outcome measures

Outcome measures
Measure	Pegcetacoplan Double Blind During Part A n=14 Participants 1080 mg, subcutaneous injection, twice weekly	Placebo Matching Pegcetacoplan-Double-blind During Part A n=7 Participants Placebo matching pegcetacoplan taken twice weekly as subcutaneous injection
Change From Baseline to Week 48 in ARC-Part B in the Absence of Intercurrent Events (ICEs)	-39.64 10^9 cells/L Standard Deviation 55.966	-118.20 10^9 cells/L Standard Deviation 73.076

SECONDARY outcome

Timeframe: Week 48

Outcome measures

Outcome measures
Measure	Pegcetacoplan Double Blind During Part A n=14 Participants 1080 mg, subcutaneous injection, twice weekly	Placebo Matching Pegcetacoplan-Double-blind During Part A n=7 Participants Placebo matching pegcetacoplan taken twice weekly as subcutaneous injection
Change From Baseline to Week 48 in D-dimer Levels-Part B in the Absence of Intercurrent Events (ICEs).	-596.63 µg/L FEU Standard Deviation 937.910	-3595.00 µg/L FEU Standard Deviation 4879.037

SECONDARY outcome

Timeframe: Week 48

Population: Part B

The ICEs of interest were : * Withdrawal from treatment or lost to follow-up before the end of the double-blind period * Use of prohibited medications (rituximab alone or in combination, any other complement inhibitor, any other investigational drug and plasma exchange. The FACT-An is used to measure quality of life (QoL) in patients with anemia. Each item is rated on a 5-point Likert scale:0=Not at all, 1=A little bit ,2=Somewhat, 3=Quite a bit, 4=Very much.Some items are reverse scored. Higher scores in this scale denote a better QoL with less impact of anemia. The total FACT-An scale score ranges from 0 to 160. The total score gives a comprehensive view of a patient's well-being. It combines the FACT-G with an Anemia subscale.FACT-G (27 items):Physical Well-Being (PWB) and Social/Family Well-Being (SWB) 14 items in total, Emotional Well-Being (EWB)-6 items, Functional Well-Being (FWB)-7 items, Anemia Subscale (AnS): 13 items. Total FACT-An score=FACT-G + Anemia Subscale=40 items

Outcome measures

Outcome measures
Measure	Pegcetacoplan Double Blind During Part A n=14 Participants 1080 mg, subcutaneous injection, twice weekly	Placebo Matching Pegcetacoplan-Double-blind During Part A n=7 Participants Placebo matching pegcetacoplan taken twice weekly as subcutaneous injection
Change From Baseline to Week 48 in FACT-An Scale Score (Quality of Life)-Part B in the Absence of Intercurrent Events (ICEs)	29.20 Units on a scale Standard Deviation 19.113	39.50 Units on a scale Standard Deviation 29.771

SECONDARY outcome

Timeframe: Week 48

Population: Part B

The ICEs of interest were : * Withdrawal from treatment or lost to follow-up before the end of the double-blind period * Use of prohibited medications (rituximab alone or in combination, any other complement inhibitor, any other investigational drug, and plasma exchange). The FACIT-F subscale is used to measure fatigue and its impact upon daily activities and function in patients with chronic illnesses and contains 20 items related to the impact of fatigue. Each item is scored on a 0-4 scale, with some items reverse-scored. Total scores range from 0 to 52, where higher scores indicate less fatigue and better outcomes, and lower scores reflect greater fatigue. It can be used alone or with other FACIT subscales as part of broader quality of life assessments.

Outcome measures

Outcome measures
Measure	Pegcetacoplan Double Blind During Part A n=14 Participants 1080 mg, subcutaneous injection, twice weekly	Placebo Matching Pegcetacoplan-Double-blind During Part A n=7 Participants Placebo matching pegcetacoplan taken twice weekly as subcutaneous injection
Change From Baseline to Week 48 in FACIT-F Subscale Score-Part B in the Absence of Intercurrent Events (ICEs).	11.82 Units on a scale Standard Deviation 11.252	21.75 Units on a scale Standard Deviation 14.315

SECONDARY outcome

Timeframe: Week 48

Outcome measures

Outcome measures
Measure	Pegcetacoplan Double Blind During Part A n=10 Participants 1080 mg, subcutaneous injection, twice weekly	Placebo Matching Pegcetacoplan-Double-blind During Part A n=4 Participants Placebo matching pegcetacoplan taken twice weekly as subcutaneous injection
Change From Baseline to Week 48 in EQ-5D-5L-Part B in the Absence of Intercurrent Events (ICEs). Mobility-Part B	0.60 Units on a scale Standard Deviation 1.174	1.25 Units on a scale Standard Deviation 1.708
Change From Baseline to Week 48 in EQ-5D-5L-Part B in the Absence of Intercurrent Events (ICEs). Self-care-Part B	0.10 Units on a scale Standard Deviation 0.316	1.25 Units on a scale Standard Deviation 0.957
Change From Baseline to Week 48 in EQ-5D-5L-Part B in the Absence of Intercurrent Events (ICEs). Usual activities-Part B	0.70 Units on a scale Standard Deviation 0.949	0.75 Units on a scale Standard Deviation 1.258
Change From Baseline to Week 48 in EQ-5D-5L-Part B in the Absence of Intercurrent Events (ICEs). Pain/Discomfort-Part B	0.40 Units on a scale Standard Deviation 0.966	1.00 Units on a scale Standard Deviation 1.414
Change From Baseline to Week 48 in EQ-5D-5L-Part B in the Absence of Intercurrent Events (ICEs). Anxiety/Depression-Part B	0.30 Units on a scale Standard Deviation 0.483	0.00 Units on a scale Standard Deviation 1.414

SECONDARY outcome

Timeframe: Week 48

The ICEs of interest were : * Withdrawal from treatment or lost to follow-up before the end of the double-blind period * Use of prohibited medications (rituximab alone or in combination, any other complement inhibitor, any other investigational drug, and plasma exchange SF-12 is a 12-item health survey assessing physical and mental health. Higher scores mean better health with scores above 50 indicating better than average health. It produces two summary scores: the Physical Component Summary (PCS) and Mental Component Summary (MCS), both norm-based (mean = 50, SD =10), with ranges of \~5-80 (PCS) and \~-3.3-80 (MCS). Higher scores = better health. It also covers 8 subscales-Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role-Emotional (RE), and Mental Health (MH), each scored between 0-100, where higher=better functioning. Scores are computed using weighted formulas from item responses (not simple averages).

Outcome measures

Outcome measures
Measure	Pegcetacoplan Double Blind During Part A n=10 Participants 1080 mg, subcutaneous injection, twice weekly	Placebo Matching Pegcetacoplan-Double-blind During Part A n=4 Participants Placebo matching pegcetacoplan taken twice weekly as subcutaneous injection
Change From Baseline to Week 48 in SF-12-Part B in the Absence of Intercurrent Events (ICEs). Physical Component Score at Week 48	7.70 units on a scale Standard Deviation 8.318	14.49 units on a scale Standard Deviation 9.197
Change From Baseline to Week 48 in SF-12-Part B in the Absence of Intercurrent Events (ICEs). Mental Component Score at Week 48	3.93 units on a scale Standard Deviation 12.465	4.10 units on a scale Standard Deviation 8.606

Adverse Events

Pegcetacoplan Double Blind During Part A

Serious events: 5 serious events

Other events: 16 other events

Deaths: 1 deaths

Placebo Matching Pegcetacoplan-Double-blind During Part A

Serious events: 1 serious events

Other events: 8 other events

Deaths: 0 deaths

Open-label Pegcetacoplan During Parts B and C

Serious events: 6 serious events

Other events: 12 other events

Deaths: 0 deaths

Open-label Pegcetacoplan (Placebo Matching Pegcetacoplan during Part A) During Parts B&C

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Luis López Lazaro

Swedish Orphan Biovitrum AB

Phone: 46733319155

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Pegcetacoplan Double Blind During Part A n=16 participants at risk Initially assigned in Part A.	Placebo Matching Pegcetacoplan-Double-blind During Part A n=8 participants at risk Initially assigned in Part A.	Open-label Pegcetacoplan During Parts B and C n=14 participants at risk Initially assigned in Part A	Open-label Pegcetacoplan (Placebo Matching Pegcetacoplan during Part A) During Parts B&C n=7 participants at risk Initially assigned in Part A
Infections and infestations Covid-19 pneumonia	6.2% 1/16 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/8 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/14 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/7 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.
Gastrointestinal disorders Cholecystitis	6.2% 1/16 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/8 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/14 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/7 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.
Infections and infestations Enterococcal sepsis	6.2% 1/16 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/8 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/14 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/7 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.
Blood and lymphatic system disorders Haemolytic anaemia	6.2% 1/16 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/8 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/14 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/7 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.
Respiratory, thoracic and mediastinal disorders Pneumonia	6.2% 1/16 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/8 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/14 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/7 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.
General disorders Syncope	6.2% 1/16 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/8 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/14 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/7 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.
Renal and urinary disorders Acute kidney injury	0.00% 0/16 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/8 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	7.1% 1/14 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/7 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.
Cardiac disorders Atrial fibrillation	0.00% 0/16 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/8 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	7.1% 1/14 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/7 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.
Blood and lymphatic system disorders Autoimmune haemolytic anaemia	0.00% 0/16 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/8 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	7.1% 1/14 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	14.3% 1/7 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.
Blood and lymphatic system disorders Breakthrough haemolysis	0.00% 0/16 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/8 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	7.1% 1/14 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/7 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.
Infections and infestations Covid-19	0.00% 0/16 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	12.5% 1/8 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/14 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/7 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.
Cardiac disorders Cardiac failure	0.00% 0/16 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/8 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	7.1% 1/14 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/7 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.
Blood and lymphatic system disorders Cold type haemolytic anaemia	0.00% 0/16 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/8 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	14.3% 2/14 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/7 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.
Blood and lymphatic system disorders Haemolysis	0.00% 0/16 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/8 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	7.1% 1/14 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/7 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.
Musculoskeletal and connective tissue disorders Osteonecrosis of jaw	0.00% 0/16 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/8 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	7.1% 1/14 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/7 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.

Other adverse events
Measure	Pegcetacoplan Double Blind During Part A n=16 participants at risk Initially assigned in Part A.	Placebo Matching Pegcetacoplan-Double-blind During Part A n=8 participants at risk Initially assigned in Part A.	Open-label Pegcetacoplan During Parts B and C n=14 participants at risk Initially assigned in Part A	Open-label Pegcetacoplan (Placebo Matching Pegcetacoplan during Part A) During Parts B&C n=7 participants at risk Initially assigned in Part A
General disorders Fatigue	18.8% 3/16 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/8 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/14 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/7 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.
General disorders Oedema peripheral	18.8% 3/16 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	37.5% 3/8 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/14 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/7 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.
General disorders Gait disturbance	0.00% 0/16 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/8 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/14 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	14.3% 1/7 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.
Infections and infestations Covid-19	18.8% 3/16 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	12.5% 1/8 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	21.4% 3/14 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/7 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.
Infections and infestations Upper respiratory tract infection	18.8% 3/16 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/8 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	7.1% 1/14 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/7 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.
Infections and infestations Nasopharyngitis	6.2% 1/16 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/8 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	7.1% 1/14 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/7 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.
Infections and infestations Pneumonia	6.2% 1/16 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/8 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	14.3% 2/14 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/7 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.
Infections and infestations Cystitis	0.00% 0/16 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/8 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/14 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	14.3% 1/7 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.
Infections and infestations Influenza	0.00% 0/16 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	12.5% 1/8 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/14 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	14.3% 1/7 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.
Infections and infestations Sinusitis	0.00% 0/16 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/8 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/14 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	14.3% 1/7 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.
Infections and infestations Urinary Tract infection	0.00% 0/16 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	12.5% 1/8 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	7.1% 1/14 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	14.3% 1/7 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.
Gastrointestinal disorders Abdominal pain	6.2% 1/16 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/8 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	7.1% 1/14 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/7 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.
Skin and subcutaneous tissue disorders Pruritus	12.5% 2/16 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/8 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	7.1% 1/14 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/7 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.
Respiratory, thoracic and mediastinal disorders Pleural effusion	12.5% 2/16 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/8 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/14 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/7 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/16 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	25.0% 2/8 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/14 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/7 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.
Blood and lymphatic system disorders Cold type haemolytic anaemia	12.5% 2/16 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/8 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	21.4% 3/14 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/7 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.
Blood and lymphatic system disorders Anaemia	0.00% 0/16 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/8 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/14 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	14.3% 1/7 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.
Blood and lymphatic system disorders Haemolysis	0.00% 0/16 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/8 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/14 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	14.3% 1/7 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.
Blood and lymphatic system disorders Hypoprothrombinaemia	0.00% 0/16 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/8 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/14 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	14.3% 1/7 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.
Musculoskeletal and connective tissue disorders Arthralgia	6.2% 1/16 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/8 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	7.1% 1/14 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/7 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.
Ear and labyrinth disorders Vertigo	6.2% 1/16 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/8 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	7.1% 1/14 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/7 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.
Investigations Gamma-glutamyltransferase increased	0.00% 0/16 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	12.5% 1/8 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/14 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/7 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.
Nervous system disorders Paraesthesia	0.00% 0/16 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	12.5% 1/8 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/14 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/7 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.
Renal and urinary disorders Ureterolithiasis	0.00% 0/16 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/8 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/14 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	14.3% 1/7 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.
General disorders Asthenia	0.00% 0/16 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	12.5% 1/8 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/14 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/7 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.
Infections and infestations Fungal skin infection	0.00% 0/16 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	12.5% 1/8 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/14 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/7 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.
Skin and subcutaneous tissue disorders Skin lesion	0.00% 0/16 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	12.5% 1/8 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/14 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/7 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.
Blood and lymphatic system disorders Haemolytic anaemia	0.00% 0/16 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	12.5% 1/8 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/14 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/7 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.
Blood and lymphatic system disorders Thrombocytosis	0.00% 0/16 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	12.5% 1/8 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/14 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/7 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.
Injury, poisoning and procedural complications Chillblains	0.00% 0/16 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	12.5% 1/8 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/14 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/7 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.
Injury, poisoning and procedural complications Cold exposure injury	0.00% 0/16 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	12.5% 1/8 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/14 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/7 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.
Metabolism and nutrition disorders Gout	0.00% 0/16 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	12.5% 1/8 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/14 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/7 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/16 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	12.5% 1/8 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/14 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/7 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.
Musculoskeletal and connective tissue disorders Bursitis	0.00% 0/16 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	12.5% 1/8 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/14 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/7 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/16 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	12.5% 1/8 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/14 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/7 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.
Musculoskeletal and connective tissue disorders Rheumatoid arthritis	0.00% 0/16 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	12.5% 1/8 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/14 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/7 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.
General disorders Chills	6.2% 1/16 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/8 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/14 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/7 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.
General disorders Induration	6.2% 1/16 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/8 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/14 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/7 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.
General disorders Injection site paraesthesia	6.2% 1/16 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/8 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/14 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/7 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.
General disorders Injection site pruritus	6.2% 1/16 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/8 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/14 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.	0.00% 0/7 • Through study completion and follow-up for up to 104 weeks (24 months approximately). All safety analyses were carried out descriptively on the safety set and presented by randomization sequence. For each output summary, all data was presented as it became available. For example, data for Part A was presented when Part A was reported. When Part B data are available, all cumulative data from Parts A and B will be reported together. The data was presented by Part A and Part B.