Trial Outcomes & Findings for HEALEY ALS Platform Trial - Regimen G DNL343 (NCT NCT05842941)

Last Updated: 2026-01-28

Results Overview

Change in disease severity as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R) total score using a Bayesian repeated measures model that accounts for loss to follow-up due to mortality. Each of 12 questions assessing distinct functional ability is scored from 4(normal) to 0 (no ability), with a maximum total score of 48 and a minimum total score of 0. Participants with higher scores have more physical function. Note that only participants who survived to their Week 24 visit contribute to the estimate.

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

249 participants

Primary outcome timeframe

Baseline to 24 Weeks

Results posted on

2026-01-28

Participant Flow

Participant milestones

Participant milestones
Measure	DNL343 DNL343 is administered orally once a day for 24 weeks.	Matching Placebo Matching Placebo is administered orally once a day for 24 weeks.
Overall Study STARTED	186	63
Overall Study COMPLETED	156	55
Overall Study NOT COMPLETED	30	8

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Number analyzed in row differs from overall number due to missing data.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	DNL343 n=186 Participants DNL343 is administered orally once a day for 24 weeks.	Matching Placebo n=63 Participants Matching Placebo is administered orally once a day for 24 weeks.	Total n=249 Participants Total of all reporting groups
Age, Continuous	59.5 Years STANDARD_DEVIATION 11.55 • n=186 Participants	57.3 Years STANDARD_DEVIATION 11.92 • n=63 Participants	58.94 Years STANDARD_DEVIATION 11.66 • n=249 Participants
Sex: Female, Male Female	82 Participants n=186 Participants	13 Participants n=63 Participants	95 Participants n=249 Participants
Sex: Female, Male Male	104 Participants n=186 Participants	50 Participants n=63 Participants	154 Participants n=249 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=186 Participants	0 Participants n=63 Participants	0 Participants n=249 Participants
Race (NIH/OMB) Asian	5 Participants n=186 Participants	1 Participants n=63 Participants	6 Participants n=249 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=186 Participants	0 Participants n=63 Participants	0 Participants n=249 Participants
Race (NIH/OMB) Black or African American	3 Participants n=186 Participants	1 Participants n=63 Participants	4 Participants n=249 Participants
Race (NIH/OMB) White	175 Participants n=186 Participants	61 Participants n=63 Participants	236 Participants n=249 Participants
Race (NIH/OMB) More than one race	1 Participants n=186 Participants	0 Participants n=63 Participants	1 Participants n=249 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=186 Participants	0 Participants n=63 Participants	2 Participants n=249 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	15 Participants n=186 Participants	5 Participants n=63 Participants	20 Participants n=249 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	169 Participants n=186 Participants	57 Participants n=63 Participants	226 Participants n=249 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=186 Participants	1 Participants n=63 Participants	3 Participants n=249 Participants
ALS Diagnosis from R El Escorial Criteria Clinically Possible ALS	20 Participants n=186 Participants	5 Participants n=63 Participants	25 Participants n=249 Participants
ALS Diagnosis from R El Escorial Criteria Clinically Probable ALS - Laboratory Supported	36 Participants n=186 Participants	10 Participants n=63 Participants	46 Participants n=249 Participants
ALS Diagnosis from R El Escorial Criteria Clinically Probable ALS	62 Participants n=186 Participants	26 Participants n=63 Participants	88 Participants n=249 Participants
ALS Diagnosis from R El Escorial Criteria Clinically Definite ALS	68 Participants n=186 Participants	22 Participants n=63 Participants	90 Participants n=249 Participants
ALS Onset Location Axial	1 Participants n=186 Participants	0 Participants n=63 Participants	1 Participants n=249 Participants
ALS Onset Location Bulbar	29 Participants n=186 Participants	6 Participants n=63 Participants	35 Participants n=249 Participants
ALS Onset Location Generalized	0 Participants n=186 Participants	0 Participants n=63 Participants	0 Participants n=249 Participants
ALS Onset Location Limb	155 Participants n=186 Participants	56 Participants n=63 Participants	211 Participants n=249 Participants
ALS Onset Location Multiple	1 Participants n=186 Participants	1 Participants n=63 Participants	2 Participants n=249 Participants
ALS Onset Location Respiratory	0 Participants n=186 Participants	0 Participants n=63 Participants	0 Participants n=249 Participants
Time Since Symptom Onset at Baseline	19.7 Months STANDARD_DEVIATION 8.05 • n=186 Participants	21.0 Months STANDARD_DEVIATION 7.91 • n=63 Participants	20.1 Months STANDARD_DEVIATION 8.02 • n=249 Participants
Delay in ALS Symptom Onset and Diagnosis	10.3 Months STANDARD_DEVIATION 6.24 • n=186 Participants	10.8 Months STANDARD_DEVIATION 5.68 • n=63 Participants	10.4 Months STANDARD_DEVIATION 6.10 • n=249 Participants
Baseline Edaravone Use Yes	115 Participants n=186 Participants	40 Participants n=63 Participants	155 Participants n=249 Participants
Baseline Edaravone Use No	71 Participants n=186 Participants	23 Participants n=63 Participants	94 Participants n=249 Participants
Baseline Riluzole Use Yes	161 Participants n=186 Participants	54 Participants n=63 Participants	215 Participants n=249 Participants
Baseline Riluzole Use No	25 Participants n=186 Participants	9 Participants n=63 Participants	34 Participants n=249 Participants
Baseline Relyvrio Use Yes	102 Participants n=186 Participants	35 Participants n=63 Participants	137 Participants n=249 Participants
Baseline Relyvrio Use No	84 Participants n=186 Participants	28 Participants n=63 Participants	112 Participants n=249 Participants
ALSFRS-R Total Score	36.0 Points STANDARD_DEVIATION 6.31 • n=186 Participants	36.0 Points STANDARD_DEVIATION 5.91 • n=63 Participants	36.0 Points STANDARD_DEVIATION 6.20 • n=249 Participants
Pre-Baseline Decline in ALSFRS-R	0.69 Points per Month STANDARD_DEVIATION 0.441 • n=186 Participants	0.70 Points per Month STANDARD_DEVIATION 0.609 • n=63 Participants	0.69 Points per Month STANDARD_DEVIATION 0.49 • n=249 Participants
SVC	85.0 Percent Predicted STANDARD_DEVIATION 18.91 • n=185 Participants • Number analyzed in row differs from overall number due to missing data.	83.6 Percent Predicted STANDARD_DEVIATION 15.05 • n=63 Participants • Number analyzed in row differs from overall number due to missing data.	84.7 Percent Predicted STANDARD_DEVIATION 17.99 • n=248 Participants • Number analyzed in row differs from overall number due to missing data.
King Stage 1 Region with Neuromuscular Dysfunction	35 Participants n=186 Participants	14 Participants n=63 Participants	49 Participants n=249 Participants
King Stage 2 Region with Neuromuscular Dysfunction	47 Participants n=186 Participants	9 Participants n=63 Participants	56 Participants n=249 Participants
King Stage 3 Region with Neuromuscular Dysfunction	52 Participants n=186 Participants	18 Participants n=63 Participants	70 Participants n=249 Participants
King Stage 4a/b Nutritional/Respiratory Failure	52 Participants n=186 Participants	22 Participants n=63 Participants	74 Participants n=249 Participants
Weight	78.5 Kg STANDARD_DEVIATION 16.49 • n=186 Participants	82.4 Kg STANDARD_DEVIATION 14.44 • n=63 Participants	79.5 Kg STANDARD_DEVIATION 16.06 • n=249 Participants
Body Mass Index	26.3 kg/m^2 STANDARD_DEVIATION 4.54 • n=186 Participants	26.3 kg/m^2 STANDARD_DEVIATION 4.05 • n=63 Participants	26.3 kg/m^2 STANDARD_DEVIATION 4.42 • n=249 Participants
Serum Creatinine Concentration	0.7 mg/dL STANDARD_DEVIATION 0.20 • n=185 Participants • Number analyzed in row differs from overall number due to missing data.	0.7 mg/dL STANDARD_DEVIATION 0.16 • n=62 Participants • Number analyzed in row differs from overall number due to missing data.	0.7 mg/dL STANDARD_DEVIATION 0.19 • n=247 Participants • Number analyzed in row differs from overall number due to missing data.
Serum NfL Concentration	61.8 ng/L n=184 Participants • Number analyzed in row differs from overall number due to missing data.	50.7 ng/L n=62 Participants • Number analyzed in row differs from overall number due to missing data.	59.0 ng/L n=246 Participants • Number analyzed in row differs from overall number due to missing data.

PRIMARY outcome

Timeframe: Baseline to 24 Weeks

Population: Outcome measure data was analyzed using the Efficacy Concurrent-controls Set (ECC), which included concurrent shared placebos from other regimens if randomized within 180 days of the first and last randomization for the applicable regimen, excluding any shared placebos also include in the focal regimen, as pre-specified in the Regimen Statistical Analysis Plan. Regimen F (NCT#05740813) and Regimen G (NCT#05842941) contributed placebo participants into the shared placebo cohort used for analysis.

Outcome measures

Outcome measures
Measure	DNL343 n=186 Participants DNL343 is administered orally once a day for 24 weeks.	Matching Placebo n=139 Participants Matching Placebo is administered orally once a day for 24 weeks.
Disease Progression as Assessed by the ALSFRS-R-Slope	-0.88 Percent change Standard Deviation 0.062	-0.84 Percent change Standard Deviation 0.081

PRIMARY outcome

Timeframe: Baseline to 24 weeks

The Mortality Rate, presented as mean deaths per month, was estimated from a Bayesian shared-parametric model that assumed exponentially distributed survival times. Mortality is defined as death or death equivalent. A participant is determined to meet the criteria of death equivalent if permanent assisted ventilation (PAV) is used for more than 22 hours per day for more than seven days in a row.

Outcome measures

Outcome measures
Measure	DNL343 n=186 Participants DNL343 is administered orally once a day for 24 weeks.	Matching Placebo n=139 Participants Matching Placebo is administered orally once a day for 24 weeks.
Mortality Event Rate	0.007 Events per month Standard Deviation 0.0021	0.007 Events per month Standard Deviation 0.0020

SECONDARY outcome

Timeframe: Baseline to 24 Weeks

Change in ALSFRS-R total score over time. Each type of function is scored from 4 (normal) to 0 (no ability), with a maximum total score of 48 and a minimum total score of 0. Participants with higher scores have more physical function.

Outcome measures

Outcome measures
Measure	DNL343 n=186 Participants DNL343 is administered orally once a day for 24 weeks.	Matching Placebo n=139 Participants Matching Placebo is administered orally once a day for 24 weeks.
ALSFRS-R Total Score	-5.759 Points Standard Deviation 0.3810	-5.726 Points Standard Deviation 0.4325

SECONDARY outcome

Timeframe: Baseline to 24 Weeks

Combined assessment of function and survival (CAFS) ranks participants' clinical outcomes based on survival time and change in the functional score. Each participant's outcome is compared to every other participant's outcome, assigned a score, and the summed scores are ranked. The mean rank score for each treatment group can then be calculated. A higher mean CAFS rank score indicates a better group outcome. The survival outcome is death or death-equivalent, where a participant is determined to meet the criteria of death equivalent if permanent assisted ventilation (PAV) is used for more than 22 hours per day for more than seven days in a row. The functional outcome is the ALS Functional Rating Scale-Revised (ALSFRS-R) score with a maximum total score of 48 and a minimum total score of 0. Participants with higher scores have more physical function.

Outcome measures

Outcome measures
Measure	DNL343 n=186 Participants DNL343 is administered orally once a day for 24 weeks.	Matching Placebo n=139 Participants Matching Placebo is administered orally once a day for 24 weeks.
Combined Assessment of Function and Survival (CAFS)	152.10 Rank Standard Error 9.622	162.39 Rank Standard Error 7.328

SECONDARY outcome

Timeframe: Baseline to 24 Weeks

Change in respiratory function over time as assessed by slow vital capacity (SVC)

Outcome measures

Outcome measures
Measure	DNL343 n=186 Participants DNL343 is administered orally once a day for 24 weeks.	Matching Placebo n=139 Participants Matching Placebo is administered orally once a day for 24 weeks.
Respiratory Function	-12.259 24-week diff. of percents of normal VC Standard Error 1.4904	-9.692 24-week diff. of percents of normal VC Standard Error 1.6572

SECONDARY outcome

Timeframe: 24 weeks

Change in upper limb muscle strength over time as measured isometrically using hand-held dynamometry and grip strength, calculated as the average percent change from baseline of the following muscles/maneuvers: shoulder flexion, elbow flexion, elbow extension, wrist extension, abductor pollicis brevis contraction, abductor digiti minimi contraction, first dorsal interosseous contraction, and grip strength. Note that only those with measurable strength at baseline were included.

Outcome measures

Outcome measures
Measure	DNL343 n=186 Participants DNL343 is administered orally once a day for 24 weeks.	Matching Placebo n=139 Participants Matching Placebo is administered orally once a day for 24 weeks.
Upper Limb Muscle Strength	-33.787 Percent change Standard Error 2.4649	-38.573 Percent change Standard Error 2.7828

SECONDARY outcome

Timeframe: Baseline to 24 weeks

The number of participants who died or met the criterion for a death equivalent from the date of their baseline visit to the end of the Week 24 visit window (generally 175 days after baseline). The death equivalent criterion is use of permanent assisted ventilation (PAV) for more than 22 hours per day for more than 7 days in a row.

Outcome measures

Outcome measures
Measure	DNL343 n=186 Participants DNL343 is administered orally once a day for 24 weeks.	Matching Placebo n=139 Participants Matching Placebo is administered orally once a day for 24 weeks.
Number of Participants With Death or Permanent Assisted Ventilation (PAV)	8 Participants	5 Participants

SECONDARY outcome

Timeframe: Baseline to 24 weeks

The number of participants who died from the date of their baseline visit to the end of the Week 24 visit window (generally 175 days after baseline).

Outcome measures

Outcome measures
Measure	DNL343 n=186 Participants DNL343 is administered orally once a day for 24 weeks.	Matching Placebo n=139 Participants Matching Placebo is administered orally once a day for 24 weeks.
Number of Participants Who Experience Death	6 Participants	4 Participants

SECONDARY outcome

Timeframe: Baseline to 24 weeks

Change in log-transformed serum neurofilament light protein (NfL) concentration from baseline to Week 24

Outcome measures

Outcome measures
Measure	DNL343 n=186 Participants DNL343 is administered orally once a day for 24 weeks.	Matching Placebo n=139 Participants Matching Placebo is administered orally once a day for 24 weeks.
Disease Progression Biomarker	0.074 ng/L Standard Error 0.0224 • Interval 1.031 to 1.125	-0.006 ng/L Standard Error 0.0256 • Interval 0.945 to 1.045

Adverse Events

DNL343

Serious events: 28 serious events

Other events: 149 other events

Deaths: 6 deaths

Matching Placebo

Serious events: 10 serious events

Other events: 43 other events

Deaths: 3 deaths

Serious adverse events

Other adverse events

Additional Information

Healey Center for ALS Project Management

Healey Center for ALS at Massachusetts General Hospital

Phone: 833-425-8257 (HALT ALS)

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	DNL343 n=186 participants at risk DNL343 is administered orally once a day for 24 weeks.	Matching Placebo n=63 participants at risk Matching Placebo is administered orally once a day for 24 weeks.
Cardiac disorders Acute myocardial infarction	0.54% 1/186 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.	0.00% 0/63 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.
Cardiac disorders Arteriospasm coronary	0.54% 1/186 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.	0.00% 0/63 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.
Cardiac disorders Bradycardia	0.54% 1/186 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.	0.00% 0/63 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.
Gastrointestinal disorders Constipation	0.54% 1/186 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.	1.6% 1/63 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.
Gastrointestinal disorders Diarrhoea	0.54% 1/186 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.	0.00% 0/63 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.
Gastrointestinal disorders Dysphagia	0.54% 1/186 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.	0.00% 0/63 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/186 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.	1.6% 1/63 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.
Gastrointestinal disorders Ileus	0.54% 1/186 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.	0.00% 0/63 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.
Gastrointestinal disorders Small intestinal obstruction	0.54% 1/186 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.	0.00% 0/63 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.
General disorders Complication associated with device	0.54% 1/186 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.	0.00% 0/63 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.
Hepatobiliary disorders Bile duct stone	0.54% 1/186 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.	0.00% 0/63 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.
Immune system disorders Drug eruption	0.54% 1/186 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.	0.00% 0/63 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.
Infections and infestations Appendicitis	0.00% 0/186 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.	1.6% 1/63 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.
Infections and infestations Bronchitis	0.00% 0/186 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.	1.6% 1/63 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.
Infections and infestations COVID-19	0.54% 1/186 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.	0.00% 0/63 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.
Infections and infestations Campylobacter infection	0.54% 1/186 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.	0.00% 0/63 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.
Infections and infestations Pneumonia	2.2% 4/186 • Number of events 4 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.	0.00% 0/63 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.
Infections and infestations Urinary tract infection	1.1% 2/186 • Number of events 2 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.	0.00% 0/63 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.
Injury, poisoning and procedural complications Facial bones fracture	0.54% 1/186 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.	0.00% 0/63 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.
Injury, poisoning and procedural complications Fall	0.54% 1/186 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.	0.00% 0/63 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.
Injury, poisoning and procedural complications Femur fracture	0.00% 0/186 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.	1.6% 1/63 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.
Injury, poisoning and procedural complications Limb traumatic amputation	0.00% 0/186 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.	1.6% 1/63 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.
Injury, poisoning and procedural complications Subdural haematoma	0.54% 1/186 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.	0.00% 0/63 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.
Injury, poisoning and procedural complications Traumatic intracranial haemorrhage	0.54% 1/186 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.	1.6% 1/63 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.
Investigations Electrocardiogram ST segment abnormal	0.54% 1/186 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.	0.00% 0/63 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.
Investigations Transaminases increased	0.54% 1/186 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.	0.00% 0/63 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.
Metabolism and nutrition disorders Dehydration	0.54% 1/186 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.	0.00% 0/63 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.
Metabolism and nutrition disorders Malnutrition	0.54% 1/186 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.	0.00% 0/63 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.
Nervous system disorders Amyotrophic lateral sclerosis	0.54% 1/186 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.	0.00% 0/63 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.
Nervous system disorders Transverse sinus thrombosis	0.00% 0/186 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.	1.6% 1/63 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.
Psychiatric disorders Suicide attempt	0.54% 1/186 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.	0.00% 0/63 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.
Renal and urinary disorders Hydronephrosis	0.00% 0/186 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.	1.6% 1/63 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.54% 1/186 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.	1.6% 1/63 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/186 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.	1.6% 1/63 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.54% 1/186 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.	0.00% 0/63 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.54% 1/186 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.	0.00% 0/63 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.54% 1/186 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.	0.00% 0/63 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.
Respiratory, thoracic and mediastinal disorders Respiratory distress	0.00% 0/186 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.	1.6% 1/63 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.
Respiratory, thoracic and mediastinal disorders Respiratory failure	1.6% 3/186 • Number of events 4 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.	1.6% 1/63 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.
Vascular disorders Shock haemorrhagic	0.54% 1/186 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.	0.00% 0/63 • Up to 35 weeks after participant signed Master Protocol consent. For safety analyses, the analysis populations include all anticipated and unanticipated safety events (i.e. Deaths, Serious Adverse Events, and Other Adverse Events) due to any cause, that occurred or worsened on or after treatment initiation to either the final safety visit, the date of death, the date of last study contact, or the date of first dose of study drug during participation in the ATE period. The all-cause mortality data was analyzed using the Efficacy Regimen Only (ERO) set, which excludes placebo participants from other regimens, and includes all anticipated and unanticipated safety events that occurred within the safety analyses time frame.