Trial Outcomes & Findings for A Study to Evaluate the Efficacy and Safety of Recombinant Human Pentraxin-2 (rhPTX-2; PRM-151) in Participants With Idiopathic Pulmonary Fibrosis (NCT NCT04552899)

NCT ID: NCT04552899

Last Updated: 2024-04-18

Results Overview

• Recruitment status: TERMINATED
• Study phase: PHASE3
• Target enrollment: 665 participants
• Primary outcome timeframe: From Baseline up to Week 52
• Results posted on: 2024-04-18

Participant Flow

A total of 665 participants were enrolled across 275 investigative sites in 29 countries.

One participant who failed screening was enrolled in error and did not subsequently enter the study.

Participant milestones

Measure	Zinpentraxin Alfa Participants received intravenous (IV) infusions of Zinpentraxin Alfa over 50-70 minutes on Days 1, 3 and 5, then followed by infusions every 4 weeks (Q4W) to Week 48.	Placebo Participants received IV infusions of placebo over 50-70 minutes on Days 1, 3 and 5, followed by infusions Q4W to Week 48.
Overall Study STARTED	331	333
Overall Study No Treatment	1	3
Overall Study COMPLETED	56	49
Overall Study NOT COMPLETED	275	284

Reasons for withdrawal

Measure	Zinpentraxin Alfa Participants received intravenous (IV) infusions of Zinpentraxin Alfa over 50-70 minutes on Days 1, 3 and 5, then followed by infusions every 4 weeks (Q4W) to Week 48.	Placebo Participants received IV infusions of placebo over 50-70 minutes on Days 1, 3 and 5, followed by infusions Q4W to Week 48.
Overall Study Adverse Event	4	3
Overall Study Death	4	4
Overall Study Lost to Follow-up	8	13
Overall Study Lung Transplant	4	3
Overall Study Participant and physician wanted to withdraw participant from study	0	1
Overall Study Physician Decision	3	4
Overall Study Study Terminated By Sponsor	237	239
Overall Study Withdrawal by Subject	15	17

Baseline Characteristics

A Study to Evaluate the Efficacy and Safety of Recombinant Human Pentraxin-2 (rhPTX-2; PRM-151) in Participants With Idiopathic Pulmonary Fibrosis

Baseline characteristics by cohort

Measure	Zinpentraxin Alfa n=331 Participants Participants received intravenous (IV) infusions of Zinpentraxin Alfa over 50-70 minutes on Days 1, 3 and 5, then followed by infusions every 4 weeks (Q4W) to Week 48.	Placebo n=333 Participants Participants received IV infusions of placebo over 50-70 minutes on Days 1, 3 and 5, followed by infusions Q4W to Week 48.	Total n=664 Participants Total of all reporting groups
Age, Continuous	70.8 Years STANDARD_DEVIATION 7.3 • n=5 Participants	70.6 Years STANDARD_DEVIATION 7.6 • n=7 Participants	70.7 Years STANDARD_DEVIATION 7.4 • n=5 Participants
Sex: Female, Male Female	61 Participants n=5 Participants	70 Participants n=7 Participants	131 Participants n=5 Participants
Sex: Female, Male Male	270 Participants n=5 Participants	263 Participants n=7 Participants	533 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	20 Participants n=5 Participants	27 Participants n=7 Participants	47 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	302 Participants n=5 Participants	299 Participants n=7 Participants	601 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	9 Participants n=5 Participants	7 Participants n=7 Participants	16 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	52 Participants n=5 Participants	56 Participants n=7 Participants	108 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	1 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) White	274 Participants n=5 Participants	270 Participants n=7 Participants	544 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants

PRIMARY outcome

Timeframe: From Baseline up to Week 52

Population: The full analysis set included all randomized participants who received at least one administration (full or partial dose) of study drug and used the grouping according to the treatment assignment at randomization.

Outcome measures

Measure	Zinpentraxin Alfa n=330 Participants Participants received intravenous (IV) infusions of Zinpentraxin Alfa over 50-70 minutes on Days 1, 3 and 5, then followed by infusions every 4 weeks (Q4W) to Week 48.	Placebo n=330 Participants Participants received IV infusions of placebo over 50-70 minutes on Days 1, 3 and 5, followed by infusions Q4W to Week 48.
Absolute Change in Forced Vital Capacity (FVC [mL])	-235.72 Milliliters (mL) Interval -283.07 to -188.4	-214.89 Milliliters (mL) Interval -262.44 to -167.3

SECONDARY outcome

Timeframe: From Baseline up to Week 52

Population: The full analysis set included all randomized participants who received at least one administration (full or partial dose) of study drug and used the grouping according to the treatment assignment at randomization.

Outcome measures

Measure	Zinpentraxin Alfa n=330 Participants Participants received intravenous (IV) infusions of Zinpentraxin Alfa over 50-70 minutes on Days 1, 3 and 5, then followed by infusions every 4 weeks (Q4W) to Week 48.	Placebo n=330 Participants Participants received IV infusions of placebo over 50-70 minutes on Days 1, 3 and 5, followed by infusions Q4W to Week 48.
Absolute Change in 6-minute Walk Distance (6MWD)	-33.64 Meters (m) Interval -48.71 to -18.57	-24.19 Meters (m) Interval -39.29 to -9.1

SECONDARY outcome

Timeframe: From Baseline up to Week 52

Population: The full analysis set included all randomized participants who received at least one administration (full or partial dose) of study drug and used the grouping according to the treatment assignment at randomization.

Outcome measures

Measure	Zinpentraxin Alfa n=330 Participants Participants received intravenous (IV) infusions of Zinpentraxin Alfa over 50-70 minutes on Days 1, 3 and 5, then followed by infusions every 4 weeks (Q4W) to Week 48.	Placebo n=330 Participants Participants received IV infusions of placebo over 50-70 minutes on Days 1, 3 and 5, followed by infusions Q4W to Week 48.
Absolute Change in FVC% Predicted	-6.22 Percent predicted Interval -7.46 to -4.98	-5.72 Percent predicted Interval -6.96 to -4.47

SECONDARY outcome

Timeframe: From Baseline up to 1 year

Population: The full analysis set included all randomized participants who received at least one administration (full or partial dose) of study drug and used the grouping according to the treatment assignment at randomization.

Outcome measures

Measure	Zinpentraxin Alfa n=330 Participants Participants received intravenous (IV) infusions of Zinpentraxin Alfa over 50-70 minutes on Days 1, 3 and 5, then followed by infusions every 4 weeks (Q4W) to Week 48.	Placebo n=330 Participants Participants received IV infusions of placebo over 50-70 minutes on Days 1, 3 and 5, followed by infusions Q4W to Week 48.
Time to Disease Progression	6.6 Months Interval 5.6 to 9.1	8.2 Months Interval 6.5 to 10.9

SECONDARY outcome

Timeframe: From Baseline up to 1 year

Population: The full analysis set included all randomized participants who received at least one administration (full or partial dose) of study drug and used the grouping according to the treatment assignment at randomization.

Outcome measures

Measure	Zinpentraxin Alfa n=330 Participants Participants received intravenous (IV) infusions of Zinpentraxin Alfa over 50-70 minutes on Days 1, 3 and 5, then followed by infusions every 4 weeks (Q4W) to Week 48.	Placebo n=330 Participants Participants received IV infusions of placebo over 50-70 minutes on Days 1, 3 and 5, followed by infusions Q4W to Week 48.
Time to First Respiratory-related Hospitalizations	NA Months NA = Not enough events available for estimation.	NA Months NA = Not enough events available for estimation.

SECONDARY outcome

Timeframe: At Baseline, Week 12, Week 24, Week 36 and Week 52

Population: The full analysis set included all randomized participants who received at least one administration (full or partial dose) of study drug and used the grouping according to the treatment assignment at randomization.

The UCSD-SOBQ is a 24-item questionnaire used to assess dyspnea severity during specific activities (21 items) and limitations caused by dyspnea in daily life (4 items). Items are assessed using a 6-point scale. Total scores, once summed, can range from 0-120 with a higher score reflecting greater dyspnea severity.

Outcome measures

Measure	Zinpentraxin Alfa n=276 Participants Participants received intravenous (IV) infusions of Zinpentraxin Alfa over 50-70 minutes on Days 1, 3 and 5, then followed by infusions every 4 weeks (Q4W) to Week 48.	Placebo n=271 Participants Participants received IV infusions of placebo over 50-70 minutes on Days 1, 3 and 5, followed by infusions Q4W to Week 48.
Change in University of California, San Diego-Shortness of Breath Questionnaire (UCSD-SOBQ) Baseline	28.9 Score on a scale Standard Deviation 22.2	29.9 Score on a scale Standard Deviation 22.6
Change in University of California, San Diego-Shortness of Breath Questionnaire (UCSD-SOBQ) Week 52	11.1 Score on a scale Standard Deviation 21.2	4.8 Score on a scale Standard Deviation 14.8
Change in University of California, San Diego-Shortness of Breath Questionnaire (UCSD-SOBQ) Week 12	0.8 Score on a scale Standard Deviation 13.0	4.0 Score on a scale Standard Deviation 17.4
Change in University of California, San Diego-Shortness of Breath Questionnaire (UCSD-SOBQ) Week 24	3.2 Score on a scale Standard Deviation 16.0	4.7 Score on a scale Standard Deviation 16.8
Change in University of California, San Diego-Shortness of Breath Questionnaire (UCSD-SOBQ) Week 36	5.4 Score on a scale Standard Deviation 17.5	6.9 Score on a scale Standard Deviation 17.7

SECONDARY outcome

Timeframe: At Baseline, Week 12, Week 24, Week 36 and Week 52

Population: The full analysis set included all randomized participants who received at least one administration (full or partial dose) of study drug and used the grouping according to the treatment assignment at randomization.

The SGRQ is a 50-item respiratory-specific quality-of-life questionnaire. The questions assess the impact of disease on activity, functionality and symptoms. Each scale is scored from 0-100. A total score represents the weighted average of these three subscores. A lower score indicates best health while a higher score indicates worst health.

Outcome measures

Measure	Zinpentraxin Alfa n=299 Participants Participants received intravenous (IV) infusions of Zinpentraxin Alfa over 50-70 minutes on Days 1, 3 and 5, then followed by infusions every 4 weeks (Q4W) to Week 48.	Placebo n=299 Participants Participants received IV infusions of placebo over 50-70 minutes on Days 1, 3 and 5, followed by infusions Q4W to Week 48.
Change in St. George Respiratory Questionnaire (SGRQ) Total Score Baseline	36.73 Score on a scale Standard Deviation 18.63	37.66 Score on a scale Standard Deviation 18.45
Change in St. George Respiratory Questionnaire (SGRQ) Total Score Week 12	1.03 Score on a scale Standard Deviation 9.98	0.81 Score on a scale Standard Deviation 10.55
Change in St. George Respiratory Questionnaire (SGRQ) Total Score Week 24	3.50 Score on a scale Standard Deviation 11.05	1.39 Score on a scale Standard Deviation 13.94
Change in St. George Respiratory Questionnaire (SGRQ) Total Score Week 36	3.21 Score on a scale Standard Deviation 11.38	2.15 Score on a scale Standard Deviation 13.42
Change in St. George Respiratory Questionnaire (SGRQ) Total Score Week 52	6.15 Score on a scale Standard Deviation 13.87	3.09 Score on a scale Standard Deviation 11.51

SECONDARY outcome

Timeframe: From Baseline up to 1 year

Population: The full analysis set included all randomized participants who received at least one administration (full or partial dose) of study drug and used the grouping according to the treatment assignment at randomization.

Outcome measures

Measure	Zinpentraxin Alfa n=330 Participants Participants received intravenous (IV) infusions of Zinpentraxin Alfa over 50-70 minutes on Days 1, 3 and 5, then followed by infusions every 4 weeks (Q4W) to Week 48.	Placebo n=330 Participants Participants received IV infusions of placebo over 50-70 minutes on Days 1, 3 and 5, followed by infusions Q4W to Week 48.
Time to First Acute Exacerbation of Idiopathic Pulmonary Fibrosis (IPF)	NA Months NA = Not enough events available for estimation.	NA Months NA = Not enough events available for estimation.

SECONDARY outcome

Timeframe: At Baseline, Week 12, Week 24, Week 36 and Week 52

Population: The full analysis set included all randomized participants who received at least one administration (full or partial dose) of study drug and used the grouping according to the treatment assignment at randomization.

Outcome measures

Measure	Zinpentraxin Alfa n=318 Participants Participants received intravenous (IV) infusions of Zinpentraxin Alfa over 50-70 minutes on Days 1, 3 and 5, then followed by infusions every 4 weeks (Q4W) to Week 48.	Placebo n=313 Participants Participants received IV infusions of placebo over 50-70 minutes on Days 1, 3 and 5, followed by infusions Q4W to Week 48.
Change in Carbon Monoxide Diffusing Capacity (DLCO) Baseline	51.73 DLCO% Predicted Standard Deviation 17.73	51.66 DLCO% Predicted Standard Deviation 14.78
Change in Carbon Monoxide Diffusing Capacity (DLCO) Week 12	-1.19 DLCO% Predicted Standard Deviation 11.89	-2.78 DLCO% Predicted Standard Deviation 9.86
Change in Carbon Monoxide Diffusing Capacity (DLCO) Week 24	-4.68 DLCO% Predicted Standard Deviation 7.93	-4.01 DLCO% Predicted Standard Deviation 9.75
Change in Carbon Monoxide Diffusing Capacity (DLCO) Week 36	-5.83 DLCO% Predicted Standard Deviation 8.49	-4.66 DLCO% Predicted Standard Deviation 7.10
Change in Carbon Monoxide Diffusing Capacity (DLCO) Week 52	-6.30 DLCO% Predicted Standard Deviation 9.56	-6.68 DLCO% Predicted Standard Deviation 9.28

SECONDARY outcome

Timeframe: From Baseline up to 1 year

Population: The full analysis set included all randomized participants who received at least one administration (full or partial dose) of study drug and used the grouping according to the treatment assignment at randomization.

Survival is measured by all-cause mortality

Outcome measures

Measure	Zinpentraxin Alfa n=330 Participants Participants received intravenous (IV) infusions of Zinpentraxin Alfa over 50-70 minutes on Days 1, 3 and 5, then followed by infusions every 4 weeks (Q4W) to Week 48.	Placebo n=330 Participants Participants received IV infusions of placebo over 50-70 minutes on Days 1, 3 and 5, followed by infusions Q4W to Week 48.
Survival	NA Months NA = Not enough events available for estimation.	NA Months NA = Not enough events available for estimation.

SECONDARY outcome

Timeframe: From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year)

Population: The safety population included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.

Outcome measures

Measure	Zinpentraxin Alfa n=331 Participants Participants received intravenous (IV) infusions of Zinpentraxin Alfa over 50-70 minutes on Days 1, 3 and 5, then followed by infusions every 4 weeks (Q4W) to Week 48.	Placebo n=329 Participants Participants received IV infusions of placebo over 50-70 minutes on Days 1, 3 and 5, followed by infusions Q4W to Week 48.
Percentage of Participants With Adverse Events (AEs)	247 Participants	238 Participants

SECONDARY outcome

Timeframe: From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year)

Population: The safety population included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.

Outcome measures

Measure	Zinpentraxin Alfa n=331 Participants Participants received intravenous (IV) infusions of Zinpentraxin Alfa over 50-70 minutes on Days 1, 3 and 5, then followed by infusions every 4 weeks (Q4W) to Week 48.	Placebo n=329 Participants Participants received IV infusions of placebo over 50-70 minutes on Days 1, 3 and 5, followed by infusions Q4W to Week 48.
Percentage of Participants With Infusion-related Reactions (IRRs) and Other Adverse Events of Special Interest	12 Participants	5 Participants

SECONDARY outcome

Timeframe: From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year)

Population: The safety population included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.

Outcome measures

Measure	Zinpentraxin Alfa n=331 Participants Participants received intravenous (IV) infusions of Zinpentraxin Alfa over 50-70 minutes on Days 1, 3 and 5, then followed by infusions every 4 weeks (Q4W) to Week 48.	Placebo n=329 Participants Participants received IV infusions of placebo over 50-70 minutes on Days 1, 3 and 5, followed by infusions Q4W to Week 48.
Percentage of Participants Permanently Discontinuing Study Treatment Due to AEs	9 Participants	6 Participants

SECONDARY outcome

Timeframe: Days 1, 5 and Weeks 4, 12, and 24

Population: The pharmacokinetic (PK) population included all randomized participants who received at least one administration (full or partial dose) of zinpentraxin alfa and at least one evaluable postdose PK sample that was above the lower limit of quantification (LLOQ).

Outcome measures

Measure	Zinpentraxin Alfa n=310 Participants Participants received intravenous (IV) infusions of Zinpentraxin Alfa over 50-70 minutes on Days 1, 3 and 5, then followed by infusions every 4 weeks (Q4W) to Week 48.	Placebo Participants received IV infusions of placebo over 50-70 minutes on Days 1, 3 and 5, followed by infusions Q4W to Week 48.
Plasma Concentrations of PRM-151 Day 1 - 1h Post Infusion	198 micrograms per millilitre (ug/mL) Standard Deviation 56.8	—
Plasma Concentrations of PRM-151 Day 1 - 2h Post Infusion	203 micrograms per millilitre (ug/mL) Standard Deviation 68.4	—
Plasma Concentrations of PRM-151 Day 1 - 4h Post Infusion	168 micrograms per millilitre (ug/mL) Standard Deviation 48.0	—
Plasma Concentrations of PRM-151 Day 1 - 8h Post Infusion	118 micrograms per millilitre (ug/mL) Standard Deviation 37.8	—
Plasma Concentrations of PRM-151 Day 1 - 10h Post Infusion	158 micrograms per millilitre (ug/mL) Standard Deviation 35.8	—
Plasma Concentrations of PRM-151 Day 1 - 12h Post Infusion	95.9 micrograms per millilitre (ug/mL) Standard Deviation 31.5	—
Plasma Concentrations of PRM-151 Day 1 - 24h Post Infusion	81.8 micrograms per millilitre (ug/mL) Standard Deviation 26.2	—
Plasma Concentrations of PRM-151 Day 5 - Pre Infusion	39.6 micrograms per millilitre (ug/mL) Standard Deviation 21.5	—
Plasma Concentrations of PRM-151 Day 5 - 2h Post Infusion	244 micrograms per millilitre (ug/mL) Standard Deviation 75.6	—
Plasma Concentrations of PRM-151 Week 4 - Pre Infusion	NA micrograms per millilitre (ug/mL) Standard Deviation NA NA = the drug level was below the limit of quantification of the assay.	—
Plasma Concentrations of PRM-151 Week 4 - 2h Post Infusion	212 micrograms per millilitre (ug/mL) Standard Deviation 105	—
Plasma Concentrations of PRM-151 Week 12 - Pre Infusion	NA micrograms per millilitre (ug/mL) Standard Deviation NA NA = the drug level was below the limit of quantification of the assay.	—
Plasma Concentrations of PRM-151 Week 12 - 2h Post Infusion	177 micrograms per millilitre (ug/mL) Standard Deviation 72.7	—
Plasma Concentrations of PRM-151 Week 24 - Pre Infusion	NA micrograms per millilitre (ug/mL) Standard Deviation NA NA = the drug level was below the limit of quantification of the assay.	—

SECONDARY outcome

Timeframe: At Baseline

Population: The immunogenicity population included all randomized participants with at least one postdose ADA assessment and were grouped according to treatment received or, if no treatment is received prior to study discontinuation, according to treatment assigned. There is no data reported for the Placebo Arm as that group never received any study drug. As such, we cannot measure anti-drug antibodies for that group of participants.

Outcome measures

Measure	Zinpentraxin Alfa n=255 Participants Participants received intravenous (IV) infusions of Zinpentraxin Alfa over 50-70 minutes on Days 1, 3 and 5, then followed by infusions every 4 weeks (Q4W) to Week 48.	Placebo Participants received IV infusions of placebo over 50-70 minutes on Days 1, 3 and 5, followed by infusions Q4W to Week 48.
Prevalence of Anti-drug Antibodies (ADAs) at Baseline	0 Participants	—

SECONDARY outcome

Timeframe: Days 1, 5 and Weeks 4, 12, 24, 36, 48, 52 and 56

Population: The immunogenicity population included all randomized participants with at least one postdose ADA assessment and were grouped according to treatment received or, if no treatment is received prior to study discontinuation, according to treatment assigned. There is no data reported for the Placebo Arm as that group never received any study drug. As such, we cannot measure anti-drug antibodies for that group of participants.

Outcome measures

Measure	Zinpentraxin Alfa n=280 Participants Participants received intravenous (IV) infusions of Zinpentraxin Alfa over 50-70 minutes on Days 1, 3 and 5, then followed by infusions every 4 weeks (Q4W) to Week 48.	Placebo Participants received IV infusions of placebo over 50-70 minutes on Days 1, 3 and 5, followed by infusions Q4W to Week 48.
Percentage of Participants With ADAs During the Study	3 Participants	—

Adverse Events

Zinpentraxin Alfa

Serious events: 46 serious events

Other events: 140 other events

Deaths: 4 deaths

Placebo

Serious events: 40 serious events

Other events: 128 other events

Deaths: 4 deaths

Serious adverse events

Measure	Zinpentraxin Alfa n=331 participants at risk Participants received intravenous (IV) infusions of Zinpentraxin Alfa over 50-70 minutes on Days 1, 3 and 5, then followed by infusions every 4 weeks (Q4W) to Week 48.	Placebo n=329 participants at risk Participants received IV infusions of placebo over 50-70 minutes on Days 1, 3 and 5, followed by infusions Q4W to Week 48.
Nervous system disorders Cerebrovascular accident	0.00% 0/331 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	0.30% 1/329 • Number of events 1 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.
Cardiac disorders Acute coronary syndrome	0.30% 1/331 • Number of events 1 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	0.00% 0/329 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.
Cardiac disorders Acute myocardial infarction	0.30% 1/331 • Number of events 1 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	0.30% 1/329 • Number of events 1 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.
Cardiac disorders Atrial fibrillation	0.30% 1/331 • Number of events 1 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	0.00% 0/329 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.
Cardiac disorders Cardiac arrest	0.30% 1/331 • Number of events 1 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	0.00% 0/329 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.
Cardiac disorders Cardiac failure	0.30% 1/331 • Number of events 2 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	0.30% 1/329 • Number of events 1 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.
Cardiac disorders Coronary artery disease	0.30% 1/331 • Number of events 1 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	0.00% 0/329 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.
Cardiac disorders Coronary artery occlusion	0.30% 1/331 • Number of events 1 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	0.00% 0/329 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.
Cardiac disorders Palpitations	0.30% 1/331 • Number of events 1 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	0.00% 0/329 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.
Eye disorders Retinal vein occlusion	0.00% 0/331 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	0.30% 1/329 • Number of events 1 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.
Gastrointestinal disorders Abdominal pain	0.30% 1/331 • Number of events 1 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	0.00% 0/329 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.
Gastrointestinal disorders Inguinal hernia	0.30% 1/331 • Number of events 1 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	0.00% 0/329 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.
Gastrointestinal disorders Intestinal obstruction	0.30% 1/331 • Number of events 1 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	0.00% 0/329 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.
Gastrointestinal disorders Mesenteric artery embolism	0.00% 0/331 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	0.30% 1/329 • Number of events 1 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.
Gastrointestinal disorders Vomiting	0.00% 0/331 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	0.30% 1/329 • Number of events 1 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.
General disorders Chest pain	0.30% 1/331 • Number of events 1 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	0.91% 3/329 • Number of events 3 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.
General disorders General physical health deterioration	0.30% 1/331 • Number of events 1 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	0.30% 1/329 • Number of events 1 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.
General disorders Hernia	0.00% 0/331 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	0.30% 1/329 • Number of events 1 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.
Hepatobiliary disorders Cholangitis	0.30% 1/331 • Number of events 1 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	0.00% 0/329 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.
Hepatobiliary disorders Cholecystitis	0.00% 0/331 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	0.30% 1/329 • Number of events 1 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.
Infections and infestations Bronchitis	0.00% 0/331 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	0.30% 1/329 • Number of events 1 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.
Infections and infestations COVID-19	0.91% 3/331 • Number of events 3 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	0.30% 1/329 • Number of events 1 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.
Infections and infestations COVID-19 pneumonia	0.00% 0/331 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	0.30% 1/329 • Number of events 1 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.
Infections and infestations Cellulitis	0.30% 1/331 • Number of events 1 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	0.00% 0/329 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.
Infections and infestations Necrotising fasciitis	0.00% 0/331 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	0.30% 1/329 • Number of events 1 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.
Infections and infestations Pneumonia	1.5% 5/331 • Number of events 5 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	0.30% 1/329 • Number of events 1 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.
Infections and infestations Pneumonia aspiration	0.00% 0/331 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	0.30% 1/329 • Number of events 1 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.
Infections and infestations Respiratory syncytial virus infection	0.00% 0/331 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	0.30% 1/329 • Number of events 1 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.
Infections and infestations Respiratory tract infection	0.30% 1/331 • Number of events 1 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	0.00% 0/329 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.
Infections and infestations Urinary tract infection	0.30% 1/331 • Number of events 1 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	0.00% 0/329 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.
Injury, poisoning and procedural complications Anastomotic ulcer	0.00% 0/331 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	0.30% 1/329 • Number of events 1 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.
Injury, poisoning and procedural complications Femur fracture	0.30% 1/331 • Number of events 1 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	0.00% 0/329 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.
Injury, poisoning and procedural complications Infusion related reaction	0.30% 1/331 • Number of events 1 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	0.00% 0/329 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.
Injury, poisoning and procedural complications Muscle injury	0.30% 1/331 • Number of events 1 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	0.00% 0/329 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.
Injury, poisoning and procedural complications Subdural haemorrhage	0.00% 0/331 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	0.30% 1/329 • Number of events 1 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.
Injury, poisoning and procedural complications Thermal burn	0.30% 1/331 • Number of events 1 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	0.00% 0/329 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.
Injury, poisoning and procedural complications Urinary retention postoperative	0.30% 1/331 • Number of events 1 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	0.00% 0/329 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/331 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	0.30% 1/329 • Number of events 1 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/331 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	0.30% 1/329 • Number of events 1 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/331 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	0.30% 1/329 • Number of events 1 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-small cell lung cancer	0.30% 1/331 • Number of events 1 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	0.00% 0/329 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic carcinoma	0.00% 0/331 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	0.30% 1/329 • Number of events 1 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.
Nervous system disorders Presyncope	0.30% 1/331 • Number of events 1 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	0.00% 0/329 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.
Nervous system disorders Syncope	0.30% 1/331 • Number of events 1 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	0.30% 1/329 • Number of events 1 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.
Nervous system disorders Transient ischaemic attack	0.00% 0/331 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	0.61% 2/329 • Number of events 2 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.
Product Issues Device dislocation	0.30% 1/331 • Number of events 1 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	0.00% 0/329 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.
Psychiatric disorders Suicide attempt	0.00% 0/331 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	0.30% 1/329 • Number of events 1 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.
Renal and urinary disorders Hydronephrosis	0.30% 1/331 • Number of events 1 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	0.00% 0/329 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.
Renal and urinary disorders Nephrolithiasis	0.00% 0/331 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	0.30% 1/329 • Number of events 1 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.
Renal and urinary disorders Renal embolism	0.00% 0/331 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	0.30% 1/329 • Number of events 1 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.
Renal and urinary disorders Renal infarct	0.00% 0/331 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	0.30% 1/329 • Number of events 1 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.
Renal and urinary disorders Ureterolithiasis	0.00% 0/331 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	0.30% 1/329 • Number of events 1 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.60% 2/331 • Number of events 2 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	0.00% 0/329 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.
Respiratory, thoracic and mediastinal disorders Cough	0.30% 1/331 • Number of events 1 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	0.00% 0/329 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.30% 1/331 • Number of events 1 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	0.61% 2/329 • Number of events 2 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.
Respiratory, thoracic and mediastinal disorders Idiopathic pulmonary fibrosis	3.6% 12/331 • Number of events 12 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	2.4% 8/329 • Number of events 8 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.30% 1/331 • Number of events 1 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	0.30% 1/329 • Number of events 1 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/331 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	0.30% 1/329 • Number of events 1 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/331 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	0.30% 1/329 • Number of events 1 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.
Respiratory, thoracic and mediastinal disorders Wheezing	0.00% 0/331 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	0.30% 1/329 • Number of events 1 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.
Vascular disorders Hypertension	0.60% 2/331 • Number of events 2 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	0.00% 0/329 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.
Vascular disorders Hypotension	0.00% 0/331 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	0.30% 1/329 • Number of events 1 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.
Vascular disorders Microscopic polyangiitis	0.00% 0/331 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	0.30% 1/329 • Number of events 1 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.

Other adverse events

Measure	Zinpentraxin Alfa n=331 participants at risk Participants received intravenous (IV) infusions of Zinpentraxin Alfa over 50-70 minutes on Days 1, 3 and 5, then followed by infusions every 4 weeks (Q4W) to Week 48.	Placebo n=329 participants at risk Participants received IV infusions of placebo over 50-70 minutes on Days 1, 3 and 5, followed by infusions Q4W to Week 48.
Gastrointestinal disorders Diarrhoea	10.6% 35/331 • Number of events 48 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	10.3% 34/329 • Number of events 39 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.
General disorders Fatigue	5.1% 17/331 • Number of events 22 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	4.3% 14/329 • Number of events 14 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.
Infections and infestations COVID-19	17.2% 57/331 • Number of events 59 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	17.3% 57/329 • Number of events 60 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.
Injury, poisoning and procedural complications Infusion related reaction	9.4% 31/331 • Number of events 42 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	8.8% 29/329 • Number of events 55 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.
Respiratory, thoracic and mediastinal disorders Cough	12.7% 42/331 • Number of events 46 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	11.6% 38/329 • Number of events 42 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.
Respiratory, thoracic and mediastinal disorders Dyspnoea	8.2% 27/331 • Number of events 29 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.	6.1% 20/329 • Number of events 22 • From Baseline up to 8 weeks after the last dose of study drug (up to an average of 1 year) All-cause mortality was reported based on randomized population =all randomized participants. SAEs \& other AEs reported based on safety-evaluable population which included all randomized participants who received at least one administration (full or partial dose) of study drug and were grouped according to the actual treatment received.

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800 821-8590

Email: genentech@druginfo.com

Results disclosure agreements

• Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
• Publication restrictions are in place

Restriction type: OTHER