Trial Outcomes & Findings for A Study to Evaluate the Efficacy and Safety of Birtamimab in Mayo Stage IV Patients With AL Amyloidosis (NCT NCT04973137)

NCT ID: NCT04973137

Last Updated: 2025-12-16

Results Overview

Comparison of time to all-cause mortality for birtamimab and placebo control.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

208 participants

Primary outcome timeframe

Time from the first dose of study drug until the pre-defined number of events (all-cause mortality) have been reached, assessed up to 39 months.

Results posted on

2025-12-16

Participant Flow

Participant milestones

Participant milestones
Measure	Birtamimab (24 mg/kg) + Standard of Care Double Blind Phase: Birtamimab, 24 mg/kg IV every 4 weeks with Standard of Care Open Label Extension Phase: Birtamimab, 24 mg/kg IV every 4 weeks with Standard of Care	Placebo + Standard of Care Double Blind Phase: Placebo 0.9% Saline IV every 4 weeks with Standard of Care Open Label Extension Phase: Birtamimab, 24 mg/kg IV every 4 weeks with Standard of Care
Double Blind Phase STARTED	139	68
Double Blind Phase COMPLETED	97	49
Double Blind Phase NOT COMPLETED	42	19
Open Label Extension Phase STARTED	92	44
Open Label Extension Phase COMPLETED	0	0
Open Label Extension Phase NOT COMPLETED	92	44

Reasons for withdrawal

Reasons for withdrawal
Measure	Birtamimab (24 mg/kg) + Standard of Care Double Blind Phase: Birtamimab, 24 mg/kg IV every 4 weeks with Standard of Care Open Label Extension Phase: Birtamimab, 24 mg/kg IV every 4 weeks with Standard of Care	Placebo + Standard of Care Double Blind Phase: Placebo 0.9% Saline IV every 4 weeks with Standard of Care Open Label Extension Phase: Birtamimab, 24 mg/kg IV every 4 weeks with Standard of Care
Double Blind Phase Adverse Event	4	0
Double Blind Phase Death	25	15
Double Blind Phase Physician Decision	5	1
Double Blind Phase Withdrawal by Subject	6	1
Double Blind Phase Other	2	2
Open Label Extension Phase Death	3	0
Open Label Extension Phase Physician Decision	0	1
Open Label Extension Phase Withdrawal by Subject	1	0
Open Label Extension Phase Study Terminated by Sponsor	83	43
Open Label Extension Phase Site Terminated by Sponsor	5	0

Baseline Characteristics

A Study to Evaluate the Efficacy and Safety of Birtamimab in Mayo Stage IV Patients With AL Amyloidosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Birtamimab (24 mg/kg) + Standard of Care n=139 Participants Birtamimab, 24 mg/kg IV every 4 weeks with Standard of Care	Placebo + Standard of Care n=68 Participants Placebo 0.9% Saline IV every 4 weeks with Standard of Care	Total n=207 Participants Total of all reporting groups
Age, Categorical Between 18 and 65 years	53 Participants n=6 Participants	31 Participants n=5 Participants	84 Participants n=5 Participants
Region of Enrollment Spain	13 participants n=6 Participants	6 participants n=5 Participants	19 participants n=5 Participants
Age, Categorical <=18 years	0 Participants n=6 Participants	0 Participants n=5 Participants	0 Participants n=5 Participants
Age, Categorical >=65 years	86 Participants n=6 Participants	37 Participants n=5 Participants	123 Participants n=5 Participants
Age, Continuous	65.7 Years STANDARD_DEVIATION 10.38 • n=6 Participants	64.1 Years STANDARD_DEVIATION 8.88 • n=5 Participants	65.2 Years STANDARD_DEVIATION 9.92 • n=5 Participants
Sex: Female, Male Female	53 Participants n=6 Participants	24 Participants n=5 Participants	77 Participants n=5 Participants
Sex: Female, Male Male	86 Participants n=6 Participants	44 Participants n=5 Participants	130 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=6 Participants	0 Participants n=5 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	27 Participants n=6 Participants	13 Participants n=5 Participants	40 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=6 Participants	0 Participants n=5 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	4 Participants n=6 Participants	6 Participants n=5 Participants	10 Participants n=5 Participants
Race (NIH/OMB) White	99 Participants n=6 Participants	44 Participants n=5 Participants	143 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=6 Participants	0 Participants n=5 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	9 Participants n=6 Participants	5 Participants n=5 Participants	14 Participants n=5 Participants
Region of Enrollment Hungary	0 participants n=6 Participants	1 participants n=5 Participants	1 participants n=5 Participants
Region of Enrollment United States	31 participants n=6 Participants	14 participants n=5 Participants	45 participants n=5 Participants
Region of Enrollment Czechia	0 participants n=6 Participants	2 participants n=5 Participants	2 participants n=5 Participants
Region of Enrollment Japan	7 participants n=6 Participants	2 participants n=5 Participants	9 participants n=5 Participants
Region of Enrollment United Kingdom	3 participants n=6 Participants	3 participants n=5 Participants	6 participants n=5 Participants
Region of Enrollment Portugal	1 participants n=6 Participants	0 participants n=5 Participants	1 participants n=5 Participants
Region of Enrollment Greece	10 participants n=6 Participants	4 participants n=5 Participants	14 participants n=5 Participants
Region of Enrollment Canada	7 participants n=6 Participants	1 participants n=5 Participants	8 participants n=5 Participants
Region of Enrollment Austria	3 participants n=6 Participants	3 participants n=5 Participants	6 participants n=5 Participants
Region of Enrollment Netherlands	7 participants n=6 Participants	4 participants n=5 Participants	11 participants n=5 Participants
Region of Enrollment South Korea	12 participants n=6 Participants	7 participants n=5 Participants	19 participants n=5 Participants
Region of Enrollment Turkey	1 participants n=6 Participants	3 participants n=5 Participants	4 participants n=5 Participants
Region of Enrollment Belgium	1 participants n=6 Participants	0 participants n=5 Participants	1 participants n=5 Participants
Region of Enrollment Taiwan	4 participants n=6 Participants	2 participants n=5 Participants	6 participants n=5 Participants
Region of Enrollment Italy	3 participants n=6 Participants	1 participants n=5 Participants	4 participants n=5 Participants
Region of Enrollment Israel	5 participants n=6 Participants	1 participants n=5 Participants	6 participants n=5 Participants
Region of Enrollment Australia	3 participants n=6 Participants	3 participants n=5 Participants	6 participants n=5 Participants
Region of Enrollment France	21 participants n=6 Participants	8 participants n=5 Participants	29 participants n=5 Participants
Region of Enrollment Germany	7 participants n=6 Participants	3 participants n=5 Participants	10 participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=6 Participants	2 Participants n=5 Participants	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	121 Participants n=6 Participants	62 Participants n=5 Participants	183 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	15 Participants n=6 Participants	4 Participants n=5 Participants	19 Participants n=5 Participants

PRIMARY outcome

Timeframe: Time from the first dose of study drug until the pre-defined number of events (all-cause mortality) have been reached, assessed up to 39 months.

Population: ITT Population

Comparison of time to all-cause mortality for birtamimab and placebo control.

Outcome measures

Outcome measures
Measure	Birtamimab (24 mg/kg) + Standard of Care n=139 Participants Birtamimab, 24 mg/kg IV every 4 weeks with Standard of Care	Placebo + Standard of Care n=68 Participants Placebo 0.9% Saline IV every 4 weeks with Standard of Care
Time to All-cause Mortality for the Double Blind Phase Number of Subjects Censored	107 Participants	51 Participants
Time to All-cause Mortality for the Double Blind Phase Event (Death) Occurred	32 Participants	17 Participants

SECONDARY outcome

Timeframe: Month 9

Population: ITT Population

Change from baseline to Month 9 in the 6-Minute Walk Test (6MWT) distance calculated as the value at 9 months minus the value at baseline.

Outcome measures

Outcome measures
Measure	Birtamimab (24 mg/kg) + Standard of Care n=139 Participants Birtamimab, 24 mg/kg IV every 4 weeks with Standard of Care	Placebo + Standard of Care n=68 Participants Placebo 0.9% Saline IV every 4 weeks with Standard of Care
6MWT Distance at Month 9	4.5 Meters Interval -52.0 to 50.5	7.75 Meters Interval -33.0 to 36.0

SECONDARY outcome

Timeframe: Month 9

Population: ITT Population

Change from baseline to Month 9 in the Short Form-36, version 2 (SF-36) calculated as the value at 9 months minus the value at baseline. SF-36 v2 is a 36-item self-administered quality-of-life questionnaire that measures health on functional status, well-being, and overall evaluation of health. The Physical Component Summary score ranges from 0 to 100 with higher scores indicating higher health-related quality of life. The Physical Component Summary is derived primarily from questions regarding physical functioning, physical problems, bodily pain, and general health questions.

Outcome measures

Outcome measures
Measure	Birtamimab (24 mg/kg) + Standard of Care n=139 Participants Birtamimab, 24 mg/kg IV every 4 weeks with Standard of Care	Placebo + Standard of Care n=68 Participants Placebo 0.9% Saline IV every 4 weeks with Standard of Care
Physical Component Summary Score of the Short Form-36, Version 2 at Month 9	1.710 Score Interval -2.695 to 6.92	4.205 Score Interval -0.43 to 10.32

Adverse Events

Birtamimab (24 mg/kg) + Standard of Care (Double-Blind Phase)

Serious events: 83 serious events

Other events: 136 other events

Deaths: 32 deaths

Placebo + Standard of Care (Double-Blind Phase)

Serious events: 39 serious events

Other events: 66 other events

Deaths: 17 deaths

Birtamimab (24 mg/kg) + Standard of Care (Open Label Extension Phase)

Serious events: 17 serious events

Other events: 53 other events

Deaths: 3 deaths

Serious adverse events

Other adverse events

Additional Information

Katelyn Diffin

Prothena Biosciences Limited

Phone: 650-837-8550

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Birtamimab (24 mg/kg) + Standard of Care (Double-Blind Phase) n=139 participants at risk Birtamimab, 24 mg/kg IV every 4 weeks with Standard of Care in Double-Blind Phase	Placebo + Standard of Care (Double-Blind Phase) n=68 participants at risk Placebo 0.9% Saline IV every 4 weeks with Standard of Care in Double-Blind Phase	Birtamimab (24 mg/kg) + Standard of Care (Open Label Extension Phase) n=136 participants at risk Birtamimab, 24 mg/kg IV every 4 weeks with Standard of Care in Open Label Extension Phase
Blood and lymphatic system disorders Anaemia	0.72% 1/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	1.5% 1/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
Cardiac disorders Cardiac failure	19.4% 27/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	20.6% 14/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	2.2% 3/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
Cardiac disorders Cardiac arrest	3.6% 5/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	7.4% 5/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
Cardiac disorders Cardiac failure congestive	2.9% 4/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	8.8% 6/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.74% 1/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
Cardiac disorders Atrial fibrillation	1.4% 2/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	2.9% 2/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.74% 1/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
Cardiac disorders Ventricular fibrillation	1.4% 2/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	1.5% 1/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
Cardiac disorders Bradycardia	1.4% 2/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
Cardiac disorders Ventricular tachycardia	1.4% 2/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
Cardiac disorders Cardiogenic shock	0.72% 1/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	2.9% 2/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
Cardiac disorders Ventricular arrhythmia	0.72% 1/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	1.5% 1/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
Cardiac disorders Atrial flutter	0.72% 1/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
Cardiac disorders Atrial thrombosis	0.72% 1/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
Cardiac disorders Cardio-respiratory arrest	0.72% 1/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
Cardiac disorders Conduction disorder	0.72% 1/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
Cardiac disorders Coronary artery disease	0.72% 1/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
Cardiac disorders Left ventricular dysfunction	0.72% 1/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
Cardiac disorders Supraventricular tachycardia	0.72% 1/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
Cardiac disorders Angina pectoris	0.00% 0/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	1.5% 1/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
Cardiac disorders Atrioventricular block first degree	0.00% 0/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	1.5% 1/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
Cardiac disorders Cardiac failure chronic	0.00% 0/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	1.5% 1/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
Cardiac disorders Tachyarrhythmia	0.00% 0/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	1.5% 1/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
Cardiac disorders Cardiac failure acute	0.00% 0/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.74% 1/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
Ear and labyrinth disorders Vertigo	0.72% 1/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
Gastrointestinal disorders Diarrhoea	1.4% 2/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	1.5% 1/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.74% 1/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal pain upper	1.4% 2/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
Gastrointestinal disorders Colitis	0.72% 1/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
Gastrointestinal disorders Enterocolitis	0.72% 1/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
Gastrointestinal disorders Ileus	0.72% 1/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
Gastrointestinal disorders Intestinal pseudo-obstruction	0.72% 1/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
Gastrointestinal disorders Ulcerative gastritis	0.72% 1/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.72% 1/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	1.5% 1/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
Gastrointestinal disorders Large intestinal stenosis	0.00% 0/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	1.5% 1/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
Gastrointestinal disorders Nausea	0.00% 0/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	1.5% 1/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
Gastrointestinal disorders Vomiting	0.00% 0/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	1.5% 1/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
Gastrointestinal disorders Inguinal hernia	0.00% 0/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.74% 1/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
General disorders Sudden death	1.4% 2/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	1.5% 1/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.74% 1/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
General disorders Pyrexia	1.4% 2/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	1.5% 1/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
General disorders Cardiac death	1.4% 2/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
General disorders Chills	1.4% 2/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.

Other adverse events
Measure	Birtamimab (24 mg/kg) + Standard of Care (Double-Blind Phase) n=139 participants at risk Birtamimab, 24 mg/kg IV every 4 weeks with Standard of Care in Double-Blind Phase	Placebo + Standard of Care (Double-Blind Phase) n=68 participants at risk Placebo 0.9% Saline IV every 4 weeks with Standard of Care in Double-Blind Phase	Birtamimab (24 mg/kg) + Standard of Care (Open Label Extension Phase) n=136 participants at risk Birtamimab, 24 mg/kg IV every 4 weeks with Standard of Care in Open Label Extension Phase
Blood and lymphatic system disorders Anaemia	24.5% 34/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	23.5% 16/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	2.2% 3/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
Blood and lymphatic system disorders Neutropenia	7.9% 11/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	8.8% 6/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
Blood and lymphatic system disorders Thrombocytopenia	7.9% 11/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	7.4% 5/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
Cardiac disorders Cardiac failure	13.7% 19/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	10.3% 7/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.74% 1/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
Cardiac disorders Atrial fibrillation	10.1% 14/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	7.4% 5/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
Cardiac disorders Angina pectoris	0.00% 0/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	7.4% 5/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
Eye disorders Dry eye	5.0% 7/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	5.9% 4/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
Gastrointestinal disorders Constipation	35.3% 49/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	35.3% 24/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
Gastrointestinal disorders Diarrhoea	28.8% 40/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	29.4% 20/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	2.9% 4/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
Gastrointestinal disorders Nausea	27.3% 38/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	36.8% 25/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
Gastrointestinal disorders Vomiting	14.4% 20/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	8.8% 6/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.74% 1/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal distension	14.4% 20/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	4.4% 3/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.74% 1/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal pain	7.2% 10/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	7.4% 5/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.74% 1/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
Gastrointestinal disorders Dyspepsia	6.5% 9/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	2.9% 2/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.74% 1/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
Gastrointestinal disorders Dry mouth	5.0% 7/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	4.4% 3/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.74% 1/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
Gastrointestinal disorders Dysphagia	5.0% 7/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	4.4% 3/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
Gastrointestinal disorders Acquired macroglossia	5.0% 7/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	2.9% 2/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.74% 1/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
Gastrointestinal disorders Ascites	5.0% 7/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal pain upper	3.6% 5/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	5.9% 4/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
General disorders Oedema peripheral	29.5% 41/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	35.3% 24/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	2.9% 4/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
General disorders Fatigue	17.3% 24/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	19.1% 13/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.74% 1/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
General disorders Pyrexia	13.7% 19/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	10.3% 7/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.74% 1/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
General disorders Asthenia	12.2% 17/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	5.9% 4/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.74% 1/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
General disorders Chills	7.9% 11/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	4.4% 3/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.74% 1/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
General disorders Influenza like illness	5.0% 7/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	5.9% 4/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.74% 1/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
General disorders Oedema	5.0% 7/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	5.9% 4/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.74% 1/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
General disorders Localised oedema	5.0% 7/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	1.5% 1/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
General disorders Non-cardiac chest pain	4.3% 6/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	5.9% 4/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.74% 1/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
Immune system disorders Hypogammaglobulinaemia	6.5% 9/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	4.4% 3/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
Infections and infestations COVID-19	13.7% 19/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	10.3% 7/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
Infections and infestations Urinary tract infection	10.8% 15/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	11.8% 8/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
Infections and infestations Upper respiratory tract infection	8.6% 12/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	13.2% 9/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	1.5% 2/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
Infections and infestations Nasopharyngitis	7.9% 11/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	8.8% 6/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	1.5% 2/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
Infections and infestations Respiratory tract infection	5.8% 8/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	5.9% 4/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.74% 1/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
Infections and infestations Pneumonia	5.0% 7/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	7.4% 5/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
Infections and infestations Bronchitis	5.0% 7/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	4.4% 3/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.74% 1/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
Infections and infestations Hordeolum	5.0% 7/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	4.4% 3/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.74% 1/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
Infections and infestations Herpes zoster	0.00% 0/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	5.9% 4/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.00% 0/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Fall	5.8% 8/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	1.5% 1/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	0.74% 1/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Contusion	5.0% 7/139 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	4.4% 3/68 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.	1.5% 2/136 • Initiation of study drug through the last study visit or up to 28 days after last dose, whichever is later, assessed up to 39 months. Safety Analysis Set included all participants who received at least one dose of study drug.