Trial Outcomes & Findings for HEALEY ALS Platform Trial - Regimen A Zilucoplan (NCT NCT04436497)

Last Updated: 2023-07-25

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. Patients with higher scores have more physical function.

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

162 participants

Primary outcome timeframe

Baseline through 24 Weeks

Results posted on

2023-07-25

Participant Flow

Participant milestones

Participant milestones
Measure	Zilucoplan Drug: Zilucoplan Administration: Subcutaneous injection Dosage: Minimum of .0.22 mg/kg daily to a maximum dose of 0.42 mg/kg daily, dependent on weight	Matching Placebo Administration: Subcutaneous injection Dosage: Daily subcutaneous injection
Overall Study STARTED	122	40
Overall Study COMPLETED	88	29
Overall Study NOT COMPLETED	34	11

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	Zilucoplan n=122 Participants Drug: Zilucoplan Administration: Subcutaneous injection Dosage: 0.3mg/kg administered daily	Matching Placebo n=40 Participants Administration: Subcutaneous injection Dosage: Daily subcutaneous injection	Total n=162 Participants Total of all reporting groups
Age, Continuous	59.5 years STANDARD_DEVIATION 10.77 • n=122 Participants	57.3 years STANDARD_DEVIATION 12.69 • n=40 Participants	58.9 years STANDARD_DEVIATION 11.27 • n=162 Participants
Sex: Female, Male Female	47 Participants n=122 Participants	16 Participants n=40 Participants	63 Participants n=162 Participants
Sex: Female, Male Male	75 Participants n=122 Participants	24 Participants n=40 Participants	99 Participants n=162 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	7 Participants n=122 Participants	2 Participants n=40 Participants	9 Participants n=162 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	113 Participants n=122 Participants	37 Participants n=40 Participants	150 Participants n=162 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=122 Participants	1 Participants n=40 Participants	3 Participants n=162 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=122 Participants	0 Participants n=40 Participants	0 Participants n=162 Participants
Race (NIH/OMB) Asian	1 Participants n=122 Participants	0 Participants n=40 Participants	1 Participants n=162 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=122 Participants	0 Participants n=40 Participants	0 Participants n=162 Participants
Race (NIH/OMB) Black or African American	2 Participants n=122 Participants	0 Participants n=40 Participants	2 Participants n=162 Participants
Race (NIH/OMB) White	115 Participants n=122 Participants	37 Participants n=40 Participants	152 Participants n=162 Participants
Race (NIH/OMB) More than one race	0 Participants n=122 Participants	0 Participants n=40 Participants	0 Participants n=162 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=122 Participants	3 Participants n=40 Participants	7 Participants n=162 Participants
El Escorial Diagnosis Clinically Definite ALS	44 Participants n=122 Participants	16 Participants n=40 Participants	60 Participants n=162 Participants
El Escorial Diagnosis Clinically Probable ALS	38 Participants n=122 Participants	7 Participants n=40 Participants	45 Participants n=162 Participants
El Escorial Diagnosis Clinically Probable ALS - Laboratory Supported	35 Participants n=122 Participants	13 Participants n=40 Participants	48 Participants n=162 Participants
El Escorial Diagnosis Clinically Possible ALS	5 Participants n=122 Participants	4 Participants n=40 Participants	9 Participants n=162 Participants
Time Since Symptom onset at Baseline	21.4 months STANDARD_DEVIATION 8.32 • n=122 Participants	22.4 months STANDARD_DEVIATION 8.95 • n=40 Participants	21.7 months STANDARD_DEVIATION 8.46 • n=162 Participants
Delay in ALS Symptom Onset and Diagnosis	10.5 months STANDARD_DEVIATION 6.39 • n=122 Participants	10.5 months STANDARD_DEVIATION 5.98 • n=40 Participants	10.5 months STANDARD_DEVIATION 6.28 • n=162 Participants
ALS Onset Location Bulbar	21 Participants n=122 Participants	6 Participants n=40 Participants	27 Participants n=162 Participants
ALS Onset Location Limb	99 Participants n=122 Participants	33 Participants n=40 Participants	132 Participants n=162 Participants
ALS Onset Location Multiple	0 Participants n=122 Participants	1 Participants n=40 Participants	1 Participants n=162 Participants
ALS Onset Location Respiratory	2 Participants n=122 Participants	0 Participants n=40 Participants	2 Participants n=162 Participants
Baseline Edaravone Use No	95 Participants n=122 Participants	30 Participants n=40 Participants	125 Participants n=162 Participants
Baseline Edaravone Use Yes	27 Participants n=122 Participants	10 Participants n=40 Participants	37 Participants n=162 Participants
Baseline Riluzole Use No	28 Participants n=122 Participants	10 Participants n=40 Participants	38 Participants n=162 Participants
Baseline Riluzole Use Yes	94 Participants n=122 Participants	30 Participants n=40 Participants	124 Participants n=162 Participants
ALSFRS-R Total Score	34.4 scores on a scale STANDARD_DEVIATION 6.42 • n=122 Participants	35.1 scores on a scale STANDARD_DEVIATION 7.12 • n=40 Participants	34.6 scores on a scale STANDARD_DEVIATION 6.58 • n=162 Participants
Change in ALSFRS-R prior to Baseline	0.75 points per month STANDARD_DEVIATION 0.539 • n=122 Participants	0.66 points per month STANDARD_DEVIATION 0.480 • n=40 Participants	0.72 points per month STANDARD_DEVIATION 0.525 • n=162 Participants
SVC	76.2 percent predicted STANDARD_DEVIATION 17.33 • n=119 Participants • Number analyzed in row differs from overall number due to missing data.	75.7 percent predicted STANDARD_DEVIATION 15.55 • n=39 Participants • Number analyzed in row differs from overall number due to missing data.	76.1 percent predicted STANDARD_DEVIATION 16.86 • n=158 Participants • Number analyzed in row differs from overall number due to missing data.
Kings Stage 1 Region with Neuromuscular Dysfunction	20 Participants n=122 Participants	9 Participants n=40 Participants	29 Participants n=162 Participants
Kings Stage 2 Regions with Neuromuscular Dysfunction	27 Participants n=122 Participants	11 Participants n=40 Participants	38 Participants n=162 Participants
Kings Stage 3 Regions with Neuromuscular Dysfunction	33 Participants n=122 Participants	6 Participants n=40 Participants	39 Participants n=162 Participants
Kings Stage 4a/b Nutritional/Respiratory Failure	42 Participants n=122 Participants	14 Participants n=40 Participants	56 Participants n=162 Participants
Weight	79.9 kg STANDARD_DEVIATION 18.30 • n=122 Participants	83.2 kg STANDARD_DEVIATION 16.71 • n=40 Participants	80.7 kg STANDARD_DEVIATION 17.92 • n=162 Participants
Body Mass Index	26.8 kg/m^2 STANDARD_DEVIATION 5.01 • n=122 Participants	28.0 kg/m^2 STANDARD_DEVIATION 5.41 • n=40 Participants	27.1 kg/m^2 STANDARD_DEVIATION 5.12 • n=162 Participants
Serum Creatinine Concentration	0.7 mg/dL STANDARD_DEVIATION 0.20 • n=122 Participants	0.7 mg/dL STANDARD_DEVIATION 0.18 • n=40 Participants	0.7 mg/dL STANDARD_DEVIATION 0.19 • n=162 Participants
Neurofilament Light (NfL) Protein in Serum	98.4 ng/L STANDARD_DEVIATION 79.00 • n=122 Participants • Number analyzed in row differs from overall number due to missing data.	86.0 ng/L STANDARD_DEVIATION 53.16 • n=38 Participants • Number analyzed in row differs from overall number due to missing data.	95.5 ng/L STANDARD_DEVIATION 73.72 • n=160 Participants • Number analyzed in row differs from overall number due to missing data.

PRIMARY outcome

Timeframe: Baseline through 24 Weeks

Population: Outcome measure data was analyzed using the Full Analysis Set, which included shared placebo from other regimens, as pre-specified in the Regimen Statistical Analysis Plan. Regimen B Verdiperstat (NCT04436510), Regimen C CNM-Au8 (NCT04414345), and Regimen D Pridopidine (NCT04615923) contributed placebo participants into the shared placebo cohort used for analysis.

Outcome measures

Outcome measures
Measure	Zilucoplan n=122 Participants Drug: Zilucoplan Administration: Subcutaneous injection Dosage: 0.3mg/kg administered daily	Matching Placebo n=164 Participants Administration: Subcutaneous injection Dosage: Daily subcutaneous injection
Disease Progression as Assessed by the ALSFRS-R Total Score	-1.11 ALSFRS-R total score points per month Standard Deviation 0.083	-1.03 ALSFRS-R total score points per month Standard Deviation 0.072

PRIMARY outcome

Timeframe: Baseline through 24 Weeks

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. The rate of mortality was estimated from a Bayesian shared-parametric model that assumed exponentially distributed survival times.

Outcome measures

Outcome measures
Measure	Zilucoplan n=122 Participants Drug: Zilucoplan Administration: Subcutaneous injection Dosage: 0.3mg/kg administered daily	Matching Placebo n=164 Participants Administration: Subcutaneous injection Dosage: Daily subcutaneous injection
Mortality Event Rate	0.009 events per month Standard Deviation 0.002	0.008 events per month Standard Deviation 0.002

SECONDARY outcome

Timeframe: Baseline and 24 Weeks

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

Outcome measures

Outcome measures
Measure	Zilucoplan n=122 Participants Drug: Zilucoplan Administration: Subcutaneous injection Dosage: 0.3mg/kg administered daily	Matching Placebo n=164 Participants Administration: Subcutaneous injection Dosage: Daily subcutaneous injection
Respiratory Function	-9.66 percent change Standard Error 1.423	-8.57 percent change Standard Error 1.159

SECONDARY outcome

Timeframe: Baseline and 24 Weeks

Change in muscle strength as measured isometrically using hand-held dynamometry (HHD).

Outcome measures

Outcome measures
Measure	Zilucoplan n=122 Participants Drug: Zilucoplan Administration: Subcutaneous injection Dosage: 0.3mg/kg administered daily	Matching Placebo n=164 Participants Administration: Subcutaneous injection Dosage: Daily subcutaneous injection
Muscle Strength	-26.20 percent change Standard Error 2.671	-25.16 percent change Standard Error 2.236

SECONDARY outcome

Timeframe: Baseline through 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	Zilucoplan n=122 Participants Drug: Zilucoplan Administration: Subcutaneous injection Dosage: 0.3mg/kg administered daily	Matching Placebo n=162 Participants Administration: Subcutaneous injection Dosage: Daily subcutaneous injection
Number of Participants That Experienced Death or Death Equivalent	6 Participants	6 Participants

Adverse Events

Zilucoplan

Serious events: 25 serious events

Other events: 115 other events

Deaths: 5 deaths

Matching Placebo

Serious events: 3 serious events

Other events: 37 other events

Deaths: 2 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

Measure	Zilucoplan n=122 participants at risk Drug: Zilucoplan Administration: Subcutaneous injection Dosage: Minimum of .0.22 mg/kg daily to a maximum dose of 0.42 mg/kg daily, dependent on weight Zilucoplan: Drug: Zilucoplan Administration: Subcutaneous injection Dosage: 0.3mg/kg administered daily	Matching Placebo n=40 participants at risk Administration: Subcutaneous injection Dosage: Daily subcutaneous injection Matching Placebo: Drug: Matching Placebo Administration: Subcutaneous injection Dosage: Daily subcutaneous injection
Respiratory, thoracic and mediastinal disorders Respiratory Failure	4.9% 6/122 • Number of events 6 • Up to 35 weeks after participant signed Master Protocol consent.	2.5% 1/40 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	2.5% 3/122 • Number of events 3 • Up to 35 weeks after participant signed Master Protocol consent.	0.00% 0/40 • Up to 35 weeks after participant signed Master Protocol consent.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	2.5% 3/122 • Number of events 3 • Up to 35 weeks after participant signed Master Protocol consent.	0.00% 0/40 • Up to 35 weeks after participant signed Master Protocol consent.
Respiratory, thoracic and mediastinal disorders Increased upper airway secretion	0.82% 1/122 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent.	0.00% 0/40 • Up to 35 weeks after participant signed Master Protocol consent.
Gastrointestinal disorders Constipation	0.82% 1/122 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent.	0.00% 0/40 • Up to 35 weeks after participant signed Master Protocol consent.
Gastrointestinal disorders Dysphagia	0.82% 1/122 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent.	0.00% 0/40 • Up to 35 weeks after participant signed Master Protocol consent.
Gastrointestinal disorders Faecaloma	0.82% 1/122 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent.	0.00% 0/40 • Up to 35 weeks after participant signed Master Protocol consent.
Gastrointestinal disorders Pancreatitis	0.82% 1/122 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent.	0.00% 0/40 • Up to 35 weeks after participant signed Master Protocol consent.
Gastrointestinal disorders Pneumoperitoneum	0.82% 1/122 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent.	0.00% 0/40 • Up to 35 weeks after participant signed Master Protocol consent.
Infections and infestations COVID-19	1.6% 2/122 • Number of events 2 • Up to 35 weeks after participant signed Master Protocol consent.	0.00% 0/40 • Up to 35 weeks after participant signed Master Protocol consent.
Infections and infestations COVID-19 pneumonia	0.82% 1/122 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent.	0.00% 0/40 • Up to 35 weeks after participant signed Master Protocol consent.
Infections and infestations Gastroenteritis	0.00% 0/122 • Up to 35 weeks after participant signed Master Protocol consent.	2.5% 1/40 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent.
Infections and infestations Pneumonia	0.82% 1/122 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent.	0.00% 0/40 • Up to 35 weeks after participant signed Master Protocol consent.
Cardiac disorders Cardiac arrest	0.82% 1/122 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent.	2.5% 1/40 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent.
Cardiac disorders Cardiac failure congestive	0.82% 1/122 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent.	0.00% 0/40 • Up to 35 weeks after participant signed Master Protocol consent.
Cardiac disorders Supraventricular tachycardia	0.82% 1/122 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent.	0.00% 0/40 • Up to 35 weeks after participant signed Master Protocol consent.
General disorders Generalised oedema	1.6% 2/122 • Number of events 2 • Up to 35 weeks after participant signed Master Protocol consent.	0.00% 0/40 • Up to 35 weeks after participant signed Master Protocol consent.
General disorders Chest pain	0.82% 1/122 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent.	0.00% 0/40 • Up to 35 weeks after participant signed Master Protocol consent.
General disorders Sudden death	0.00% 0/122 • Up to 35 weeks after participant signed Master Protocol consent.	2.5% 1/40 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oesophageal carcinoma	0.82% 1/122 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent.	0.00% 0/40 • Up to 35 weeks after participant signed Master Protocol consent.
Product Issues Device malfunction	0.82% 1/122 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent.	0.00% 0/40 • Up to 35 weeks after participant signed Master Protocol consent.
Vascular disorders Deep vein thrombosis	0.82% 1/122 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent.	0.00% 0/40 • Up to 35 weeks after participant signed Master Protocol consent.

Measure	Zilucoplan n=122 participants at risk Drug: Zilucoplan Administration: Subcutaneous injection Dosage: Minimum of .0.22 mg/kg daily to a maximum dose of 0.42 mg/kg daily, dependent on weight Zilucoplan: Drug: Zilucoplan Administration: Subcutaneous injection Dosage: 0.3mg/kg administered daily	Matching Placebo n=40 participants at risk Administration: Subcutaneous injection Dosage: Daily subcutaneous injection Matching Placebo: Drug: Matching Placebo Administration: Subcutaneous injection Dosage: Daily subcutaneous injection
Nervous system disorders Muscular weakness	23.8% 29/122 • Number of events 45 • Up to 35 weeks after participant signed Master Protocol consent.	20.0% 8/40 • Number of events 11 • Up to 35 weeks after participant signed Master Protocol consent.
Nervous system disorders Neuromyopathy	18.0% 22/122 • Number of events 27 • Up to 35 weeks after participant signed Master Protocol consent.	12.5% 5/40 • Number of events 14 • Up to 35 weeks after participant signed Master Protocol consent.
Nervous system disorders Headache	11.5% 14/122 • Number of events 21 • Up to 35 weeks after participant signed Master Protocol consent.	10.0% 4/40 • Number of events 4 • Up to 35 weeks after participant signed Master Protocol consent.
Nervous system disorders Dizziness	9.8% 12/122 • Number of events 14 • Up to 35 weeks after participant signed Master Protocol consent.	5.0% 2/40 • Number of events 3 • Up to 35 weeks after participant signed Master Protocol consent.
Nervous system disorders Dysarthria	7.4% 9/122 • Number of events 9 • Up to 35 weeks after participant signed Master Protocol consent.	5.0% 2/40 • Number of events 2 • Up to 35 weeks after participant signed Master Protocol consent.
Nervous system disorders Tension headache	4.9% 6/122 • Number of events 6 • Up to 35 weeks after participant signed Master Protocol consent.	5.0% 2/40 • Number of events 3 • Up to 35 weeks after participant signed Master Protocol consent.
Injury, poisoning and procedural complications Fall	32.0% 39/122 • Number of events 76 • Up to 35 weeks after participant signed Master Protocol consent.	22.5% 9/40 • Number of events 18 • Up to 35 weeks after participant signed Master Protocol consent.
Injury, poisoning and procedural complications Injection site bruising	18.0% 22/122 • Number of events 24 • Up to 35 weeks after participant signed Master Protocol consent.	15.0% 6/40 • Number of events 7 • Up to 35 weeks after participant signed Master Protocol consent.
Injury, poisoning and procedural complications Injection site pain	14.8% 18/122 • Number of events 23 • Up to 35 weeks after participant signed Master Protocol consent.	5.0% 2/40 • Number of events 2 • Up to 35 weeks after participant signed Master Protocol consent.
Injury, poisoning and procedural complications Contusion	5.7% 7/122 • Number of events 7 • Up to 35 weeks after participant signed Master Protocol consent.	5.0% 2/40 • Number of events 2 • Up to 35 weeks after participant signed Master Protocol consent.
Injury, poisoning and procedural complications Injection site reaction	3.3% 4/122 • Number of events 4 • Up to 35 weeks after participant signed Master Protocol consent.	5.0% 2/40 • Number of events 2 • Up to 35 weeks after participant signed Master Protocol consent.
Injury, poisoning and procedural complications Traumatic haematoma	0.82% 1/122 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent.	5.0% 2/40 • Number of events 2 • Up to 35 weeks after participant signed Master Protocol consent.
Gastrointestinal disorders Constipation	10.7% 13/122 • Number of events 15 • Up to 35 weeks after participant signed Master Protocol consent.	7.5% 3/40 • Number of events 5 • Up to 35 weeks after participant signed Master Protocol consent.
Gastrointestinal disorders Dysphagia	9.8% 12/122 • Number of events 13 • Up to 35 weeks after participant signed Master Protocol consent.	10.0% 4/40 • Number of events 4 • Up to 35 weeks after participant signed Master Protocol consent.
Gastrointestinal disorders Nausea	8.2% 10/122 • Number of events 12 • Up to 35 weeks after participant signed Master Protocol consent.	7.5% 3/40 • Number of events 3 • Up to 35 weeks after participant signed Master Protocol consent.
Gastrointestinal disorders Diarrhoea	6.6% 8/122 • Number of events 9 • Up to 35 weeks after participant signed Master Protocol consent.	7.5% 3/40 • Number of events 3 • Up to 35 weeks after participant signed Master Protocol consent.
Gastrointestinal disorders Salivary hypersecretion	3.3% 4/122 • Number of events 4 • Up to 35 weeks after participant signed Master Protocol consent.	7.5% 3/40 • Number of events 3 • Up to 35 weeks after participant signed Master Protocol consent.
General disorders Fatigue	13.9% 17/122 • Number of events 18 • Up to 35 weeks after participant signed Master Protocol consent.	12.5% 5/40 • Number of events 5 • Up to 35 weeks after participant signed Master Protocol consent.
General disorders Oedema peripheral	7.4% 9/122 • Number of events 10 • Up to 35 weeks after participant signed Master Protocol consent.	2.5% 1/40 • Number of events 3 • Up to 35 weeks after participant signed Master Protocol consent.
Infections and infestations Urinary tract infection	4.9% 6/122 • Number of events 7 • Up to 35 weeks after participant signed Master Protocol consent.	12.5% 5/40 • Number of events 5 • Up to 35 weeks after participant signed Master Protocol consent.
Infections and infestations COVID-19	2.5% 3/122 • Number of events 3 • Up to 35 weeks after participant signed Master Protocol consent.	10.0% 4/40 • Number of events 4 • Up to 35 weeks after participant signed Master Protocol consent.
Respiratory, thoracic and mediastinal disorders Cough	6.6% 8/122 • Number of events 9 • Up to 35 weeks after participant signed Master Protocol consent.	2.5% 1/40 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent.
Respiratory, thoracic and mediastinal disorders Dyspnoea	5.7% 7/122 • Number of events 8 • Up to 35 weeks after participant signed Master Protocol consent.	5.0% 2/40 • Number of events 2 • Up to 35 weeks after participant signed Master Protocol consent.
Skin and subcutaneous tissue disorders Pruritus	5.7% 7/122 • Number of events 7 • Up to 35 weeks after participant signed Master Protocol consent.	5.0% 2/40 • Number of events 3 • Up to 35 weeks after participant signed Master Protocol consent.
Skin and subcutaneous tissue disorders Rash	5.7% 7/122 • Number of events 7 • Up to 35 weeks after participant signed Master Protocol consent.	2.5% 1/40 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent.
Musculoskeletal and connective tissue disorders Pain in extremity	4.1% 5/122 • Number of events 9 • Up to 35 weeks after participant signed Master Protocol consent.	5.0% 2/40 • Number of events 2 • Up to 35 weeks after participant signed Master Protocol consent.
Musculoskeletal and connective tissue disorders Arthralgia	4.1% 5/122 • Number of events 5 • Up to 35 weeks after participant signed Master Protocol consent.	5.0% 2/40 • Number of events 2 • Up to 35 weeks after participant signed Master Protocol consent.
Psychiatric disorders Anxiety	5.7% 7/122 • Number of events 8 • Up to 35 weeks after participant signed Master Protocol consent.	2.5% 1/40 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent.
Metabolism and nutrition disorders Decreased appetite	4.9% 6/122 • Number of events 6 • Up to 35 weeks after participant signed Master Protocol consent.	12.5% 5/40 • Number of events 6 • Up to 35 weeks after participant signed Master Protocol consent.
Vascular disorders Hypertension	4.1% 5/122 • Number of events 5 • Up to 35 weeks after participant signed Master Protocol consent.	5.0% 2/40 • Number of events 2 • Up to 35 weeks after participant signed Master Protocol consent.
Ear and labyrinth disorders Tinnitus	0.82% 1/122 • Number of events 2 • Up to 35 weeks after participant signed Master Protocol consent.	5.0% 2/40 • Number of events 2 • Up to 35 weeks after participant signed Master Protocol consent.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/122 • Up to 35 weeks after participant signed Master Protocol consent.	5.0% 2/40 • Number of events 2 • Up to 35 weeks after participant signed Master Protocol consent.
Injury, poisoning and procedural complications Post-traumatic pain	2.5% 3/122 • Number of events 3 • Up to 35 weeks after participant signed Master Protocol consent.	5.0% 2/40 • Number of events 2 • Up to 35 weeks after participant signed Master Protocol consent.
Gastrointestinal disorders Vomiting	0.82% 1/122 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent.	5.0% 2/40 • Number of events 2 • Up to 35 weeks after participant signed Master Protocol consent.
Investigations Hepatic enzyme increased	0.82% 1/122 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent.	5.0% 2/40 • Number of events 2 • Up to 35 weeks after participant signed Master Protocol consent.