Trial Outcomes & Findings for HEALEY ALS Platform Trial - Regimen B Verdiperstat (NCT NCT04436510)

Last Updated: 2023-06-12

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

167 participants

Primary outcome timeframe

Baseline to 24 Weeks

Results posted on

2023-06-12

Participant Flow

Participant milestones

Participant milestones
Measure	Verdiperstat Verdiperstat is administered twice daily p.o. for 24 weeks. Verdiperstat: Drug: Verdiperstat Administration: Oral Dose: 600mg twice daily	Matching Placebo Matching placebo is administered twice daily p.o. for 24 weeks. Matching Placebo: Drug: Matching Placebo Administration: Oral Dose: two tablets twice daily
Overall Study STARTED	126	41
Overall Study COMPLETED	95	35
Overall Study NOT COMPLETED	31	6

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	Verdiperstat n=126 Participants Verdiperstat is administered twice daily p.o. for 24 weeks. Verdiperstat: Drug: Verdiperstat Administration: Oral Dose: 600mg twice daily	Matching Placebo n=41 Participants Matching placebo is administered twice daily p.o. for 24 weeks. Matching Placebo: Drug: Matching Placebo Administration: Oral Dose: two tablets twice daily	Total n=167 Participants Total of all reporting groups
Age, Continuous	58.1 years STANDARD_DEVIATION 11.54 • n=126 Participants	57.3 years STANDARD_DEVIATION 11.07 • n=41 Participants	57.9 years STANDARD_DEVIATION 11.40 • n=167 Participants
Sex: Female, Male Female	47 Participants n=126 Participants	12 Participants n=41 Participants	59 Participants n=167 Participants
Sex: Female, Male Male	79 Participants n=126 Participants	29 Participants n=41 Participants	108 Participants n=167 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	8 Participants n=126 Participants	0 Participants n=41 Participants	8 Participants n=167 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	116 Participants n=126 Participants	41 Participants n=41 Participants	157 Participants n=167 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=126 Participants	0 Participants n=41 Participants	2 Participants n=167 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=126 Participants	0 Participants n=41 Participants	0 Participants n=167 Participants
Race (NIH/OMB) Asian	5 Participants n=126 Participants	1 Participants n=41 Participants	6 Participants n=167 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=126 Participants	0 Participants n=41 Participants	0 Participants n=167 Participants
Race (NIH/OMB) Black or African American	4 Participants n=126 Participants	2 Participants n=41 Participants	6 Participants n=167 Participants
Race (NIH/OMB) White	116 Participants n=126 Participants	37 Participants n=41 Participants	153 Participants n=167 Participants
Race (NIH/OMB) More than one race	1 Participants n=126 Participants	0 Participants n=41 Participants	1 Participants n=167 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=126 Participants	1 Participants n=41 Participants	1 Participants n=167 Participants
El Escorial Diagnosis Clinically Definite ALS	45 Participants n=126 Participants	18 Participants n=41 Participants	63 Participants n=167 Participants
El Escorial Diagnosis Clinically Probable ALS	53 Participants n=126 Participants	11 Participants n=41 Participants	64 Participants n=167 Participants
El Escorial Diagnosis Clinically Probable ALS - Laboratory Supported	20 Participants n=126 Participants	8 Participants n=41 Participants	28 Participants n=167 Participants
El Escorial Diagnosis Clinically Possible ALS	8 Participants n=126 Participants	4 Participants n=41 Participants	12 Participants n=167 Participants
Time Since Symptom onset at Baseline	21.2 months STANDARD_DEVIATION 8.93 • n=126 Participants	22.5 months STANDARD_DEVIATION 7.91 • n=41 Participants	21.5 months STANDARD_DEVIATION 8.69 • n=167 Participants
Delay in ALS Symptom Onset and Diagnosis	10.5 months STANDARD_DEVIATION 5.96 • n=126 Participants	10.5 months STANDARD_DEVIATION 6.15 • n=41 Participants	10.5 months STANDARD_DEVIATION 5.99 • n=167 Participants
ALS Onset Location Axial	1 Participants n=126 Participants	2 Participants n=41 Participants	3 Participants n=167 Participants
ALS Onset Location Bulbar	20 Participants n=126 Participants	7 Participants n=41 Participants	27 Participants n=167 Participants
ALS Onset Location Generalized	1 Participants n=126 Participants	0 Participants n=41 Participants	1 Participants n=167 Participants
ALS Onset Location Limb	103 Participants n=126 Participants	32 Participants n=41 Participants	135 Participants n=167 Participants
ALS Onset Location Respiratory	1 Participants n=126 Participants	0 Participants n=41 Participants	1 Participants n=167 Participants
Baseline Edaravone Use Yes	28 Participants n=126 Participants	11 Participants n=41 Participants	39 Participants n=167 Participants
Baseline Edaravone Use No	98 Participants n=126 Participants	30 Participants n=41 Participants	128 Participants n=167 Participants
Baseline Riluzole Use Yes	95 Participants n=126 Participants	31 Participants n=41 Participants	126 Participants n=167 Participants
Baseline Riluzole Use No	31 Participants n=126 Participants	10 Participants n=41 Participants	41 Participants n=167 Participants
ALSFRS-R Total Score	34.3 scores on a scale STANDARD_DEVIATION 6.45 • n=126 Participants	34.3 scores on a scale STANDARD_DEVIATION 6.88 • n=41 Participants	34.3 scores on a scale STANDARD_DEVIATION 6.54 • n=167 Participants
Change in ALSFRS-R prior to Baseline	0.75 points per month STANDARD_DEVIATION 0.499 • n=126 Participants	0.64 points per month STANDARD_DEVIATION 0.303 • n=41 Participants	0.72 points per month STANDARD_DEVIATION 0.461 • n=167 Participants
SVC	77.2 Percent Predicted STANDARD_DEVIATION 20.37 • n=121 Participants • Number analyzed in row differs from overall number due to missing data.	74.5 Percent Predicted STANDARD_DEVIATION 17.50 • n=39 Participants • Number analyzed in row differs from overall number due to missing data.	76.6 Percent Predicted STANDARD_DEVIATION 19.69 • n=160 Participants • Number analyzed in row differs from overall number due to missing data.
Kings Stage 1 Region with Neuromuscular Dysfunction	13 Participants n=126 Participants	9 Participants n=41 Participants	22 Participants n=167 Participants
Kings Stage 2 Regions with Neuromuscular Dysfunction	39 Participants n=126 Participants	10 Participants n=41 Participants	49 Participants n=167 Participants
Kings Stage 3 Regions with Neuromuscular Dysfunction	36 Participants n=126 Participants	14 Participants n=41 Participants	50 Participants n=167 Participants
Kings Stage 4a/b Nutritional/Respiratory Failure	2 Participants n=126 Participants	0 Participants n=41 Participants	2 Participants n=167 Participants
Kings Stage 4b Respiratory Failure	36 Participants n=126 Participants	8 Participants n=41 Participants	44 Participants n=167 Participants
Weight	78.7 kg STANDARD_DEVIATION 17.44 • n=126 Participants	82.4 kg STANDARD_DEVIATION 18.66 • n=41 Participants	79.6 kg STANDARD_DEVIATION 17.76 • n=167 Participants
Body Mass Index	26.4 kg/m^2 STANDARD_DEVIATION 5.13 • n=126 Participants	27.1 kg/m^2 STANDARD_DEVIATION 4.89 • n=41 Participants	26.6 kg/m^2 STANDARD_DEVIATION 5.07 • n=167 Participants
Serum Creatinine Concentration	0.7 mg/dL STANDARD_DEVIATION 0.17 • n=126 Participants	0.7 mg/dL STANDARD_DEVIATION 0.17 • n=41 Participants	0.7 mg/dL STANDARD_DEVIATION 0.17 • n=167 Participants
Neurofilament Light (NfL) Protein in Serum	92.3 ng/L STANDARD_DEVIATION 75.27 • n=124 Participants • Number analyzed in row differs from overall number due to missing data.	65.8 ng/L STANDARD_DEVIATION 25.60 • n=40 Participants • Number analyzed in row differs from overall number due to missing data.	85.9 ng/L STANDARD_DEVIATION 67.55 • n=164 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 Full Analysis Set, which included shared placebo from other regimens, as pre-specified in the Regimen Statistical Analysis Plan. Regimen A Zilucoplan (NCT04436497) and Regimen C CNM-Au8 (NCT04414345) contributed placebo participants into the shared placebo cohort used for analysis.

Outcome measures

Outcome measures
Measure	Verdiperstat n=126 Participants Verdiperstat is administered twice daily p.o. for 24 weeks. Verdiperstat: Drug: Verdiperstat Administration: Oral Dose: 600mg twice daily	Matching Placebo n=122 Participants Matching placebo is administered twice daily p.o. for 24 weeks. Matching Placebo: Drug: Matching Placebo Administration: Oral Dose: two tablets twice daily
Disease Progression as Assessed by the ALSFRS-R-Slope	-1.02 ALSFRS-R total score points per month Standard Deviation 0.091	-1.05 ALSFRS-R total score points per month Standard Deviation 0.086

PRIMARY outcome

Timeframe: Baseline to 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	Verdiperstat n=126 Participants Verdiperstat is administered twice daily p.o. for 24 weeks. Verdiperstat: Drug: Verdiperstat Administration: Oral Dose: 600mg twice daily	Matching Placebo n=122 Participants Matching placebo is administered twice daily p.o. for 24 weeks. Matching Placebo: Drug: Matching Placebo Administration: Oral Dose: two tablets twice daily
Mortality Even Rate	0.011 events per month Standard Deviation 0.003	0.012 events per month Standard Deviation 0.003

SECONDARY outcome

Timeframe: Baseline to 24 Weeks

Change in respiratory function over time as measured by Slow Vital Capacity (SVC).

Outcome measures

Outcome measures
Measure	Verdiperstat n=126 Participants Verdiperstat is administered twice daily p.o. for 24 weeks. Verdiperstat: Drug: Verdiperstat Administration: Oral Dose: 600mg twice daily	Matching Placebo n=122 Participants Matching placebo is administered twice daily p.o. for 24 weeks. Matching Placebo: Drug: Matching Placebo Administration: Oral Dose: two tablets twice daily
Respiratory Function	-7.76 percent change Standard Error 1.519	-8.05 percent change Standard Error 1.418

SECONDARY outcome

Timeframe: Baseline to 24 Weeks

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

Outcome measures

Outcome measures
Measure	Verdiperstat n=126 Participants Verdiperstat is administered twice daily p.o. for 24 weeks. Verdiperstat: Drug: Verdiperstat Administration: Oral Dose: 600mg twice daily	Matching Placebo n=122 Participants Matching placebo is administered twice daily p.o. for 24 weeks. Matching Placebo: Drug: Matching Placebo Administration: Oral Dose: two tablets twice daily
Muscle Strength	-23.24 percent change Standard Error 2.863	-26.81 percent change Standard Error 2.682

SECONDARY outcome

Timeframe: 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	Verdiperstat n=126 Participants Verdiperstat is administered twice daily p.o. for 24 weeks. Verdiperstat: Drug: Verdiperstat Administration: Oral Dose: 600mg twice daily	Matching Placebo n=122 Participants Matching placebo is administered twice daily p.o. for 24 weeks. Matching Placebo: Drug: Matching Placebo Administration: Oral Dose: two tablets twice daily
Number of Participants That Experienced Death or Death Equivalent	7 Participants	5 Participants

Adverse Events

Verdiperstat

Serious events: 20 serious events

Other events: 114 other events

Deaths: 6 deaths

Matching Placebo

Serious events: 2 serious events

Other events: 37 other events

Deaths: 0 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	Verdiperstat n=126 participants at risk Verdiperstat is administered twice daily p.o. for 24 weeks. Verdiperstat: Drug: Verdiperstat Administration: Oral Dose: 600mg twice daily	Matching Placebo n=41 participants at risk Matching placebo is administered twice daily p.o. for 24 weeks. Matching Placebo: Drug: Matching Placebo Administration: Oral Dose: two tablets twice daily
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	2.4% 3/126 • Number of events 3 • Up to 35 weeks after participant signed Master Protocol consent.	0.00% 0/41 • Up to 35 weeks after participant signed Master Protocol consent.
Respiratory, thoracic and mediastinal disorders Respiratory failure	1.6% 2/126 • Number of events 3 • Up to 35 weeks after participant signed Master Protocol consent.	0.00% 0/41 • Up to 35 weeks after participant signed Master Protocol consent.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.79% 1/126 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent.	0.00% 0/41 • Up to 35 weeks after participant signed Master Protocol consent.
Nervous system disorders Amyotrophic lateral sclerosis	1.6% 2/126 • Number of events 2 • Up to 35 weeks after participant signed Master Protocol consent.	0.00% 0/41 • Up to 35 weeks after participant signed Master Protocol consent.
Nervous system disorders Aphasia	0.79% 1/126 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent.	0.00% 0/41 • Up to 35 weeks after participant signed Master Protocol consent.
Nervous system disorders Cerebral infarction	0.79% 1/126 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent.	0.00% 0/41 • Up to 35 weeks after participant signed Master Protocol consent.
Nervous system disorders Syncope	0.00% 0/126 • Up to 35 weeks after participant signed Master Protocol consent.	2.4% 1/41 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent.
Infections and infestations Bacteraemia	0.79% 1/126 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent.	0.00% 0/41 • Up to 35 weeks after participant signed Master Protocol consent.
Infections and infestations Bacterial sepsis	0.79% 1/126 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent.	0.00% 0/41 • Up to 35 weeks after participant signed Master Protocol consent.
Infections and infestations COVID-19	0.79% 1/126 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent.	0.00% 0/41 • Up to 35 weeks after participant signed Master Protocol consent.
Infections and infestations COVID-19 pneumonia	0.79% 1/126 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent.	0.00% 0/41 • Up to 35 weeks after participant signed Master Protocol consent.
Blood and lymphatic system disorders Febrile neutropenia	1.6% 2/126 • Number of events 2 • Up to 35 weeks after participant signed Master Protocol consent.	0.00% 0/41 • Up to 35 weeks after participant signed Master Protocol consent.
Gastrointestinal disorders Abdominal pain	0.79% 1/126 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent.	0.00% 0/41 • Up to 35 weeks after participant signed Master Protocol consent.
Gastrointestinal disorders Ileus	0.79% 1/126 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent.	0.00% 0/41 • Up to 35 weeks after participant signed Master Protocol consent.
Metabolism and nutrition disorders Dehydration	0.79% 1/126 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent.	0.00% 0/41 • Up to 35 weeks after participant signed Master Protocol consent.
Metabolism and nutrition disorders Failure to thrive	0.79% 1/126 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent.	0.00% 0/41 • Up to 35 weeks after participant signed Master Protocol consent.
Vascular disorders Deep vein thrombosis	0.79% 1/126 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent.	2.4% 1/41 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent.
General disorders Sudden death	0.79% 1/126 • Up to 35 weeks after participant signed Master Protocol consent.	0.00% 0/41 • Up to 35 weeks after participant signed Master Protocol consent.
Injury, poisoning and procedural complications Hip fracture	0.79% 1/126 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent.	0.00% 0/41 • Up to 35 weeks after participant signed Master Protocol consent.
Investigations Hepatic enzyme abnormal	0.79% 1/126 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent.	0.00% 0/41 • Up to 35 weeks after participant signed Master Protocol consent.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) B-cell lymphoma	0.79% 1/126 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent.	0.00% 0/41 • Up to 35 weeks after participant signed Master Protocol consent.

Measure	Verdiperstat n=126 participants at risk Verdiperstat is administered twice daily p.o. for 24 weeks. Verdiperstat: Drug: Verdiperstat Administration: Oral Dose: 600mg twice daily	Matching Placebo n=41 participants at risk Matching placebo is administered twice daily p.o. for 24 weeks. Matching Placebo: Drug: Matching Placebo Administration: Oral Dose: two tablets twice daily
Nervous system disorders Headache	21.4% 27/126 • Number of events 31 • Up to 35 weeks after participant signed Master Protocol consent.	22.0% 9/41 • Number of events 11 • Up to 35 weeks after participant signed Master Protocol consent.
Nervous system disorders Muscular weakness	17.5% 22/126 • Number of events 35 • Up to 35 weeks after participant signed Master Protocol consent.	29.3% 12/41 • Number of events 18 • Up to 35 weeks after participant signed Master Protocol consent.
Nervous system disorders Neuromyopathy	12.7% 16/126 • Number of events 22 • Up to 35 weeks after participant signed Master Protocol consent.	19.5% 8/41 • Number of events 9 • Up to 35 weeks after participant signed Master Protocol consent.
Nervous system disorders Tension headache	10.3% 13/126 • Number of events 17 • Up to 35 weeks after participant signed Master Protocol consent.	7.3% 3/41 • Number of events 7 • Up to 35 weeks after participant signed Master Protocol consent.
Nervous system disorders Dizziness	10.3% 13/126 • Number of events 15 • Up to 35 weeks after participant signed Master Protocol consent.	7.3% 3/41 • Number of events 3 • Up to 35 weeks after participant signed Master Protocol consent.
Nervous system disorders Dysarthria	3.2% 4/126 • Number of events 4 • Up to 35 weeks after participant signed Master Protocol consent.	7.3% 3/41 • Number of events 4 • Up to 35 weeks after participant signed Master Protocol consent.
Gastrointestinal disorders Nausea	27.8% 35/126 • Number of events 40 • Up to 35 weeks after participant signed Master Protocol consent.	7.3% 3/41 • Number of events 3 • Up to 35 weeks after participant signed Master Protocol consent.
Gastrointestinal disorders Constipation	19.0% 24/126 • Number of events 26 • Up to 35 weeks after participant signed Master Protocol consent.	19.5% 8/41 • Number of events 8 • Up to 35 weeks after participant signed Master Protocol consent.
Gastrointestinal disorders Dysphagia	9.5% 12/126 • Number of events 13 • Up to 35 weeks after participant signed Master Protocol consent.	9.8% 4/41 • Number of events 6 • Up to 35 weeks after participant signed Master Protocol consent.
Gastrointestinal disorders Salivary hypersecretion	7.9% 10/126 • Number of events 10 • Up to 35 weeks after participant signed Master Protocol consent.	4.9% 2/41 • Number of events 2 • Up to 35 weeks after participant signed Master Protocol consent.
Gastrointestinal disorders Diarrhoea	7.9% 10/126 • Number of events 12 • Up to 35 weeks after participant signed Master Protocol consent.	2.4% 1/41 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent.
General disorders Fatigue	15.9% 20/126 • Number of events 21 • Up to 35 weeks after participant signed Master Protocol consent.	26.8% 11/41 • Number of events 14 • Up to 35 weeks after participant signed Master Protocol consent.
General disorders Oedema peripheral	5.6% 7/126 • Number of events 8 • Up to 35 weeks after participant signed Master Protocol consent.	9.8% 4/41 • Number of events 4 • Up to 35 weeks after participant signed Master Protocol consent.
Injury, poisoning and procedural complications Fall	19.0% 24/126 • Number of events 50 • Up to 35 weeks after participant signed Master Protocol consent.	22.0% 9/41 • Number of events 16 • Up to 35 weeks after participant signed Master Protocol consent.
Respiratory, thoracic and mediastinal disorders Dyspnoea	7.9% 10/126 • Number of events 11 • Up to 35 weeks after participant signed Master Protocol consent.	4.9% 2/41 • Number of events 2 • Up to 35 weeks after participant signed Master Protocol consent.
Respiratory, thoracic and mediastinal disorders Cough	5.6% 7/126 • Number of events 7 • Up to 35 weeks after participant signed Master Protocol consent.	2.4% 1/41 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent.
Psychiatric disorders Insomnia	19.8% 25/126 • Number of events 28 • Up to 35 weeks after participant signed Master Protocol consent.	0.00% 0/41 • Up to 35 weeks after participant signed Master Protocol consent.
Psychiatric disorders Anxiety	7.1% 9/126 • Number of events 9 • Up to 35 weeks after participant signed Master Protocol consent.	2.4% 1/41 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent.
Infections and infestations Urinary tract infection	7.9% 10/126 • Number of events 11 • Up to 35 weeks after participant signed Master Protocol consent.	9.8% 4/41 • Number of events 4 • Up to 35 weeks after participant signed Master Protocol consent.
Musculoskeletal and connective tissue disorders Back pain	5.6% 7/126 • Number of events 9 • Up to 35 weeks after participant signed Master Protocol consent.	4.9% 2/41 • Number of events 8 • Up to 35 weeks after participant signed Master Protocol consent.
Musculoskeletal and connective tissue disorders Arthralgia	5.6% 7/126 • Number of events 11 • Up to 35 weeks after participant signed Master Protocol consent.	2.4% 1/41 • Number of events 1 • Up to 35 weeks after participant signed Master Protocol consent.
Musculoskeletal and connective tissue disorders Pain in extremity	3.2% 4/126 • Number of events 4 • Up to 35 weeks after participant signed Master Protocol consent.	7.3% 3/41 • Number of events 4 • Up to 35 weeks after participant signed Master Protocol consent.
Investigations Blood thyroid stimulating hormone increased	8.7% 11/126 • Number of events 12 • Up to 35 weeks after participant signed Master Protocol consent.	0.00% 0/41 • Up to 35 weeks after participant signed Master Protocol consent.
Renal and urinary disorders Urine odour abnormal	6.3% 8/126 • Number of events 8 • Up to 35 weeks after participant signed Master Protocol consent.	0.00% 0/41 • Up to 35 weeks after participant signed Master Protocol consent.
Metabolism and nutrition disorders Decreased appetite	10.3% 13/126 • Number of events 13 • Up to 35 weeks after participant signed Master Protocol consent.	4.9% 2/41 • Number of events 2 • Up to 35 weeks after participant signed Master Protocol consent.