Trial Outcomes & Findings for Placebo-controlled Efficacy and Safety Study of GSK3511294 (Depemokimab) in Participants With Severe Asthma With an Eosinophilic Phenotype (NCT NCT04719832)

NCT ID: NCT04719832

Last Updated: 2024-12-17

Results Overview

Clinically significant exacerbations recorded were defined as worsening of asthma requiring the use of systemic corticosteroids (CS) \[such as intramuscular (IM), intravenous (IV) or oral\] and/or hospitalization and/or Emergency Department (ED) visit. For all participants, IV or oral steroids (e.g., prednisone) for at least 3 days or a single IM corticosteroid dose is required. For participants on maintenance systemic corticosteroids, at least double the existing maintenance dose for at least 3 days is required. Exacerbations recorded in the electronic case report form (eCRF) were considered as verified clinically significant exacerbations and included in the primary analysis. Exacerbations separated by less than 7 days was treated as a continuation of the same exacerbation.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

395 participants

Primary outcome timeframe

Up to Week 52

Results posted on

2024-12-17

Participant Flow

A total of 395 participants were randomized to the study. Of which 382 participants were included in Full analysis set (FAS) population. FAS included all randomized participants who received at least 1 dose of study intervention excluding 11 participants from 1 site with Good Clinical Practice (GCP)/data integrity issues. Two (2) participants were randomized in error and did not receive any study drug.

A total of 395 were randomized in the study.

Participant milestones

Participant milestones
Measure	Placebo Participants received placebo subcutaneous (SC) injection once every 26 weeks (week 0 and week 26). Participants were to be maintained on their existing baseline maintenance asthma standard of care (SOC) treatment throughout the study.	GSK3511294 Participants received a 100 milligram (mg) dose of GSK3511294 SC injection once every 26 weeks (week 0 and week 26). Participants were to be maintained on their existing baseline maintenance asthma SOC treatment throughout the study.
Overall Study STARTED	136	259
Overall Study Full Analysis Population	132	250
Overall Study COMPLETED	122	237
Overall Study NOT COMPLETED	14	22

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received placebo subcutaneous (SC) injection once every 26 weeks (week 0 and week 26). Participants were to be maintained on their existing baseline maintenance asthma standard of care (SOC) treatment throughout the study.	GSK3511294 Participants received a 100 milligram (mg) dose of GSK3511294 SC injection once every 26 weeks (week 0 and week 26). Participants were to be maintained on their existing baseline maintenance asthma SOC treatment throughout the study.
Overall Study Adverse Event	2	0
Overall Study Lack of Efficacy	2	4
Overall Study Lost to Follow-up	0	2
Overall Study Physician Decision	0	1
Overall Study Pregnancy	1	1
Overall Study Withdrawal by Subject	5	5
Overall Study Randomized, not treated	0	2
Overall Study GCP violations	4	7

Baseline Characteristics

Placebo-controlled Efficacy and Safety Study of GSK3511294 (Depemokimab) in Participants With Severe Asthma With an Eosinophilic Phenotype

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=132 Participants Participants received placebo SC injection once every 26 weeks (week 0 and week 26). Participants were to be maintained on their existing baseline maintenance asthma SOC treatment throughout the study.	GSK3511294 n=250 Participants Participants received a 100 mg dose of GSK3511294 SC injection once every 26 weeks (week 0 and week 26). Participants were to be maintained on their existing baseline maintenance asthma SOC treatment throughout the study.	Total n=382 Participants Total of all reporting groups
Age, Continuous	53.6 years STANDARD_DEVIATION 14.91 • n=5 Participants	54.1 years STANDARD_DEVIATION 13.82 • n=7 Participants	53.9 years STANDARD_DEVIATION 14.19 • n=5 Participants
Sex: Female, Male Female	79 Participants n=5 Participants	144 Participants n=7 Participants	223 Participants n=5 Participants
Sex: Female, Male Male	53 Participants n=5 Participants	106 Participants n=7 Participants	159 Participants n=5 Participants
Race/Ethnicity, Customized White	109 Participants n=5 Participants	207 Participants n=7 Participants	316 Participants n=5 Participants
Race/Ethnicity, Customized Others	23 Participants n=5 Participants	43 Participants n=7 Participants	66 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to Week 52

Population: The FAS included all randomized participants who received at least one dose of study intervention excluding participants from 1 site with GCP violation. Participants were analyzed according to the intervention they were allocated at randomization. Only those participants who were measured and analyzed (i.e., contributed data reported in the table) were included in the Overall Number of Participants Analyzed field. 'Number Analyzed' signifies participants evaluable for specified time points.

Outcome measures

Outcome measures
Measure	Placebo n=132 Participants Participants received placebo SC injection once every 26 weeks (week 0 and week 26). Participants were to be maintained on their existing baseline maintenance asthma SOC treatment throughout the study.	GSK3511294 n=249 Participants Participants received a 100 mg dose of GSK3511294 SC injection once every 26 weeks (week 0 and week 26). Participants were to be maintained on their existing baseline maintenance asthma SOC treatment throughout the study.
Annualized Rate of Clinically Significant Exacerbations up to 52 Weeks	1.11 Exacerbation per participant per year 95% Confidence Interval 0.86 • Interval 0.86 to 1.43	0.46 Exacerbation per participant per year 95% Confidence Interval 0.36 • Interval 0.36 to 0.58

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 52

The SGRQ is a 50-item patient-reported outcome tool used to measure Quality of Life in participants with airway obstruction diseases. The questions are designed to be self-completed by the participant. The total score was calculated by the symptom score, activity and impact score; and summarizing the impact of the disease on overall health status on 0-100 rating scale. Scores are expressed as a percentage of overall impairment where 100 representing worst possible health status and 0 indicating best possible health status. Higher scores indicating greater impairment of quality of life. Change from Baseline was defined as value at the indicated time point minus Baseline value.

Outcome measures

Outcome measures
Measure	Placebo n=128 Participants Participants received placebo SC injection once every 26 weeks (week 0 and week 26). Participants were to be maintained on their existing baseline maintenance asthma SOC treatment throughout the study.	GSK3511294 n=240 Participants Participants received a 100 mg dose of GSK3511294 SC injection once every 26 weeks (week 0 and week 26). Participants were to be maintained on their existing baseline maintenance asthma SOC treatment throughout the study.
Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score at Week 52	-9.67 Scores on a scale Standard Error 1.544 • Interval 1.544 to	-13.03 Scores on a scale Standard Error 1.112 • Interval 1.112 to

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 52

The ACQ-5 is a five-item questionnaire developed as a measure of participants asthma symptom control. The questions are designed to be self-completed by the participant. The 5 questions enquired to recall how their asthma had been during the previous week and to respond about the frequency and/or severity of symptoms (nocturnal awakening, waking in the morning, activity limitation, shortness of breath and wheezing). The overall ACQ-5 response option is the mean score of all 5 questions representing 0 with no impairment/limitation and 6 as total impairment/ limitation. Higher scores indicated more limitations and lower score with better asthma control. Change from Baseline was defined as value at the indicated time point minus Baseline value.

Outcome measures

Outcome measures
Measure	Placebo n=129 Participants Participants received placebo SC injection once every 26 weeks (week 0 and week 26). Participants were to be maintained on their existing baseline maintenance asthma SOC treatment throughout the study.	GSK3511294 n=241 Participants Participants received a 100 mg dose of GSK3511294 SC injection once every 26 weeks (week 0 and week 26). Participants were to be maintained on their existing baseline maintenance asthma SOC treatment throughout the study.
Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score at Week 52	-0.77 Scores on a Scale Standard Error 0.091 • Interval 0.091 to	-0.82 Scores on a Scale Standard Error 0.066 • Interval 0.066 to

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 52

Forced Expiratory Volume in One Second (FEV1) is defined as the volume of air that can be forced out in one second after taking a deep breath by a person and will be measured by spirometry testing. Change from Baseline in clinic pre-bronchodilator FEV1 was determined. Change from Baseline was defined as value at the indicated time point minus Baseline value.

Outcome measures

Outcome measures
Measure	Placebo n=126 Participants Participants received placebo SC injection once every 26 weeks (week 0 and week 26). Participants were to be maintained on their existing baseline maintenance asthma SOC treatment throughout the study.	GSK3511294 n=236 Participants Participants received a 100 mg dose of GSK3511294 SC injection once every 26 weeks (week 0 and week 26). Participants were to be maintained on their existing baseline maintenance asthma SOC treatment throughout the study.
Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in One Second (FEV1) At Week 52	0.160 Liters (L) Standard Error 0.0364 • Interval 0.0364 to	0.160 Liters (L) Standard Error 0.0263 • Interval 0.0263 to

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: All participants in the FAS population (excluding participants from 1 site with GCP violation) for whom at least one ANSD questionnaire was administered. Participants were analyzed according to the intervention they were allocated at randomization. Only those participants who were measured and analyzed (i.e., contributed data reported in the table) were included in the Overall Number of Participants Analyzed field. 'Number Analyzed' signifies participants evaluable for specified time points.

The ANSD is a 6-item self-administered patient reported diary developed by Patient Related Outcomes (PRO) Consortium's Asthma Working Group to facilitate comprehensive and reliable assessment of asthma symptoms from a participant's perspective. Participants were required to rate the severity of symptoms in 3 core categories: breathing symptoms (wheezing, shortness of breath), chest symptoms (chest tightness, chest pain) and cough. The ANSD was to be completed before going to bed and refers to asthma symptoms during the day. Symptoms are rated at their worst using an 11-point numeric rating scale ranging from 0 (None) to 10 (As bad as you can imagine). Higher scores indicate more severe symptoms. Mean daily scores of ANSD was calculated by weekly intervals. The baseline values were defined as the average score from Day -7 to Day -1 inclusive (at least 4 days must be non-missing). Change from Baseline was defined as value at each time point minus Baseline value.

Outcome measures

Outcome measures
Measure	Placebo n=95 Participants Participants received placebo SC injection once every 26 weeks (week 0 and week 26). Participants were to be maintained on their existing baseline maintenance asthma SOC treatment throughout the study.	GSK3511294 n=185 Participants Participants received a 100 mg dose of GSK3511294 SC injection once every 26 weeks (week 0 and week 26). Participants were to be maintained on their existing baseline maintenance asthma SOC treatment throughout the study.
Change From Baseline in Asthma Nighttime Symptom Diary (ANSD) Weekly Mean Score at Week 52	-1.30 Scores on a Scale Standard Error 0.168	-1.39 Scores on a Scale Standard Error 0.120

SECONDARY outcome

Timeframe: Baseline to Week 52

Population: All participants in the FAS population (excluding participants from 1 site with GCP violation) for whom at least one ADSD questionnaire was administered. Participants were analyzed according to the intervention they were allocated at randomization. Only those participants who were measured and analyzed (i.e., contributed data reported in the table) were included in the Overall Number of Participants Analyzed field. 'Number Analyzed' signifies participants evaluable for specified time points.

The ADSD is a 6-item self-administered patient reported diary developed by patient related outcomes (PRO) Consortium's Asthma Working Group to facilitate comprehensive and reliable assessment of asthma symptoms from a participant's perspective. Participants were required to rate the severity of symptoms in 3 core categories: breathing symptoms (wheezing, shortness of breath), chest symptoms (chest tightness, chest pain) and cough. The ADSD was to be completed upon waking and refers to asthma symptoms during the night-time. Symptoms are rated at their worst using an 11-point numeric rating scale ranging from 0 (None) to 10 (As bad as you can imagine). Higher scores indicate more severe symptoms. Mean daily scores of ADSD was calculated by weekly intervals. The baseline values were defined as the average score from Day -7 to Day -1 inclusive (at least 4 days must be non-missing). Change from Baseline was defined as value at each time point minus Baseline value.

Outcome measures

Outcome measures
Measure	Placebo n=110 Participants Participants received placebo SC injection once every 26 weeks (week 0 and week 26). Participants were to be maintained on their existing baseline maintenance asthma SOC treatment throughout the study.	GSK3511294 n=206 Participants Participants received a 100 mg dose of GSK3511294 SC injection once every 26 weeks (week 0 and week 26). Participants were to be maintained on their existing baseline maintenance asthma SOC treatment throughout the study.
Change From Baseline in Asthma Daily Symptom Diary (ADSD) Weekly Mean Score at Week 52	-1.25 Scores on a Scale Standard Error 0.140	-1.33 Scores on a Scale Standard Error 0.101

SECONDARY outcome

Timeframe: Up to Week 52

Population: Full analysis set included all randomized participants who received at least 1 dose of study intervention excluding participants from 1 site with GCP violation. Participants were analyzed according to the intervention they were allocated at randomization.

The data did not meet the condition (total of 20 or more exacerbations requiring hospitalization and/or ED visit) for conducting the statistical analysis. The number of exacerbations requiring Hospitalization and/or ED Visit are reported here.

Outcome measures

Outcome measures
Measure	Placebo n=132 Participants Participants received placebo SC injection once every 26 weeks (week 0 and week 26). Participants were to be maintained on their existing baseline maintenance asthma SOC treatment throughout the study.	GSK3511294 n=250 Participants Participants received a 100 mg dose of GSK3511294 SC injection once every 26 weeks (week 0 and week 26). Participants were to be maintained on their existing baseline maintenance asthma SOC treatment throughout the study.
Annualized Rate of Exacerbations Requiring Hospitalization and/or Emergency Department (ED) Visit up to 52 Weeks	13 Exacerbations	5 Exacerbations

Adverse Events

Placebo

Serious events: 22 serious events

Other events: 78 other events

Deaths: 0 deaths

GSK3511294

Serious events: 15 serious events

Other events: 145 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 8664357343

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=132 participants at risk Participants received placebo SC injection once every 26 weeks (week 0 and week 26). Participants were to be maintained on their existing baseline maintenance asthma SOC treatment throughout the study.	GSK3511294 n=250 participants at risk Participants received a 100 mg dose of GSK3511294 SC injection once every 26 weeks (week 0 and week 26). Participants were to be maintained on their existing baseline maintenance asthma SOC treatment throughout the study.
Gastrointestinal disorders Gastrooesophageal reflux disease	3.0% 4/132 • Number of events 4 • All-cause mortality, Serious adverse events (SAEs) and non-serious adverse events (Non-SAEs) were collected from the start of the study intervention (Day 1) till follow up week 56. All-cause mortality, SAEs and Non-SAEs were reported for the Safety Population which included all randomized participants who received at least 1 dose of study treatment excluding participants from 1 site with GCP violation. AEs were reported treatment-wise.	0.80% 2/250 • Number of events 3 • All-cause mortality, Serious adverse events (SAEs) and non-serious adverse events (Non-SAEs) were collected from the start of the study intervention (Day 1) till follow up week 56. All-cause mortality, SAEs and Non-SAEs were reported for the Safety Population which included all randomized participants who received at least 1 dose of study treatment excluding participants from 1 site with GCP violation. AEs were reported treatment-wise.
Infections and infestations Bronchitis	3.8% 5/132 • Number of events 5 • All-cause mortality, Serious adverse events (SAEs) and non-serious adverse events (Non-SAEs) were collected from the start of the study intervention (Day 1) till follow up week 56. All-cause mortality, SAEs and Non-SAEs were reported for the Safety Population which included all randomized participants who received at least 1 dose of study treatment excluding participants from 1 site with GCP violation. AEs were reported treatment-wise.	4.8% 12/250 • Number of events 18 • All-cause mortality, Serious adverse events (SAEs) and non-serious adverse events (Non-SAEs) were collected from the start of the study intervention (Day 1) till follow up week 56. All-cause mortality, SAEs and Non-SAEs were reported for the Safety Population which included all randomized participants who received at least 1 dose of study treatment excluding participants from 1 site with GCP violation. AEs were reported treatment-wise.
Infections and infestations COVID-19	20.5% 27/132 • Number of events 30 • All-cause mortality, Serious adverse events (SAEs) and non-serious adverse events (Non-SAEs) were collected from the start of the study intervention (Day 1) till follow up week 56. All-cause mortality, SAEs and Non-SAEs were reported for the Safety Population which included all randomized participants who received at least 1 dose of study treatment excluding participants from 1 site with GCP violation. AEs were reported treatment-wise.	20.4% 51/250 • Number of events 51 • All-cause mortality, Serious adverse events (SAEs) and non-serious adverse events (Non-SAEs) were collected from the start of the study intervention (Day 1) till follow up week 56. All-cause mortality, SAEs and Non-SAEs were reported for the Safety Population which included all randomized participants who received at least 1 dose of study treatment excluding participants from 1 site with GCP violation. AEs were reported treatment-wise.
Infections and infestations Influenza	1.5% 2/132 • Number of events 2 • All-cause mortality, Serious adverse events (SAEs) and non-serious adverse events (Non-SAEs) were collected from the start of the study intervention (Day 1) till follow up week 56. All-cause mortality, SAEs and Non-SAEs were reported for the Safety Population which included all randomized participants who received at least 1 dose of study treatment excluding participants from 1 site with GCP violation. AEs were reported treatment-wise.	7.6% 19/250 • Number of events 21 • All-cause mortality, Serious adverse events (SAEs) and non-serious adverse events (Non-SAEs) were collected from the start of the study intervention (Day 1) till follow up week 56. All-cause mortality, SAEs and Non-SAEs were reported for the Safety Population which included all randomized participants who received at least 1 dose of study treatment excluding participants from 1 site with GCP violation. AEs were reported treatment-wise.
Infections and infestations Laryngitis	3.0% 4/132 • Number of events 4 • All-cause mortality, Serious adverse events (SAEs) and non-serious adverse events (Non-SAEs) were collected from the start of the study intervention (Day 1) till follow up week 56. All-cause mortality, SAEs and Non-SAEs were reported for the Safety Population which included all randomized participants who received at least 1 dose of study treatment excluding participants from 1 site with GCP violation. AEs were reported treatment-wise.	3.6% 9/250 • Number of events 9 • All-cause mortality, Serious adverse events (SAEs) and non-serious adverse events (Non-SAEs) were collected from the start of the study intervention (Day 1) till follow up week 56. All-cause mortality, SAEs and Non-SAEs were reported for the Safety Population which included all randomized participants who received at least 1 dose of study treatment excluding participants from 1 site with GCP violation. AEs were reported treatment-wise.
Infections and infestations Lower respiratory tract infection	3.8% 5/132 • Number of events 7 • All-cause mortality, Serious adverse events (SAEs) and non-serious adverse events (Non-SAEs) were collected from the start of the study intervention (Day 1) till follow up week 56. All-cause mortality, SAEs and Non-SAEs were reported for the Safety Population which included all randomized participants who received at least 1 dose of study treatment excluding participants from 1 site with GCP violation. AEs were reported treatment-wise.	4.0% 10/250 • Number of events 10 • All-cause mortality, Serious adverse events (SAEs) and non-serious adverse events (Non-SAEs) were collected from the start of the study intervention (Day 1) till follow up week 56. All-cause mortality, SAEs and Non-SAEs were reported for the Safety Population which included all randomized participants who received at least 1 dose of study treatment excluding participants from 1 site with GCP violation. AEs were reported treatment-wise.
Infections and infestations Nasopharyngitis	18.9% 25/132 • Number of events 32 • All-cause mortality, Serious adverse events (SAEs) and non-serious adverse events (Non-SAEs) were collected from the start of the study intervention (Day 1) till follow up week 56. All-cause mortality, SAEs and Non-SAEs were reported for the Safety Population which included all randomized participants who received at least 1 dose of study treatment excluding participants from 1 site with GCP violation. AEs were reported treatment-wise.	11.6% 29/250 • Number of events 37 • All-cause mortality, Serious adverse events (SAEs) and non-serious adverse events (Non-SAEs) were collected from the start of the study intervention (Day 1) till follow up week 56. All-cause mortality, SAEs and Non-SAEs were reported for the Safety Population which included all randomized participants who received at least 1 dose of study treatment excluding participants from 1 site with GCP violation. AEs were reported treatment-wise.
Infections and infestations Pharyngitis	1.5% 2/132 • Number of events 2 • All-cause mortality, Serious adverse events (SAEs) and non-serious adverse events (Non-SAEs) were collected from the start of the study intervention (Day 1) till follow up week 56. All-cause mortality, SAEs and Non-SAEs were reported for the Safety Population which included all randomized participants who received at least 1 dose of study treatment excluding participants from 1 site with GCP violation. AEs were reported treatment-wise.	3.2% 8/250 • Number of events 8 • All-cause mortality, Serious adverse events (SAEs) and non-serious adverse events (Non-SAEs) were collected from the start of the study intervention (Day 1) till follow up week 56. All-cause mortality, SAEs and Non-SAEs were reported for the Safety Population which included all randomized participants who received at least 1 dose of study treatment excluding participants from 1 site with GCP violation. AEs were reported treatment-wise.
Infections and infestations Respiratory tract infection	4.5% 6/132 • Number of events 11 • All-cause mortality, Serious adverse events (SAEs) and non-serious adverse events (Non-SAEs) were collected from the start of the study intervention (Day 1) till follow up week 56. All-cause mortality, SAEs and Non-SAEs were reported for the Safety Population which included all randomized participants who received at least 1 dose of study treatment excluding participants from 1 site with GCP violation. AEs were reported treatment-wise.	3.2% 8/250 • Number of events 9 • All-cause mortality, Serious adverse events (SAEs) and non-serious adverse events (Non-SAEs) were collected from the start of the study intervention (Day 1) till follow up week 56. All-cause mortality, SAEs and Non-SAEs were reported for the Safety Population which included all randomized participants who received at least 1 dose of study treatment excluding participants from 1 site with GCP violation. AEs were reported treatment-wise.
Infections and infestations Rhinitis	7.6% 10/132 • Number of events 16 • All-cause mortality, Serious adverse events (SAEs) and non-serious adverse events (Non-SAEs) were collected from the start of the study intervention (Day 1) till follow up week 56. All-cause mortality, SAEs and Non-SAEs were reported for the Safety Population which included all randomized participants who received at least 1 dose of study treatment excluding participants from 1 site with GCP violation. AEs were reported treatment-wise.	6.0% 15/250 • Number of events 17 • All-cause mortality, Serious adverse events (SAEs) and non-serious adverse events (Non-SAEs) were collected from the start of the study intervention (Day 1) till follow up week 56. All-cause mortality, SAEs and Non-SAEs were reported for the Safety Population which included all randomized participants who received at least 1 dose of study treatment excluding participants from 1 site with GCP violation. AEs were reported treatment-wise.
Infections and infestations Sinusitis	4.5% 6/132 • Number of events 6 • All-cause mortality, Serious adverse events (SAEs) and non-serious adverse events (Non-SAEs) were collected from the start of the study intervention (Day 1) till follow up week 56. All-cause mortality, SAEs and Non-SAEs were reported for the Safety Population which included all randomized participants who received at least 1 dose of study treatment excluding participants from 1 site with GCP violation. AEs were reported treatment-wise.	4.4% 11/250 • Number of events 14 • All-cause mortality, Serious adverse events (SAEs) and non-serious adverse events (Non-SAEs) were collected from the start of the study intervention (Day 1) till follow up week 56. All-cause mortality, SAEs and Non-SAEs were reported for the Safety Population which included all randomized participants who received at least 1 dose of study treatment excluding participants from 1 site with GCP violation. AEs were reported treatment-wise.
Infections and infestations Upper respiratory tract infection	10.6% 14/132 • Number of events 22 • All-cause mortality, Serious adverse events (SAEs) and non-serious adverse events (Non-SAEs) were collected from the start of the study intervention (Day 1) till follow up week 56. All-cause mortality, SAEs and Non-SAEs were reported for the Safety Population which included all randomized participants who received at least 1 dose of study treatment excluding participants from 1 site with GCP violation. AEs were reported treatment-wise.	10.0% 25/250 • Number of events 39 • All-cause mortality, Serious adverse events (SAEs) and non-serious adverse events (Non-SAEs) were collected from the start of the study intervention (Day 1) till follow up week 56. All-cause mortality, SAEs and Non-SAEs were reported for the Safety Population which included all randomized participants who received at least 1 dose of study treatment excluding participants from 1 site with GCP violation. AEs were reported treatment-wise.
Musculoskeletal and connective tissue disorders Back pain	5.3% 7/132 • Number of events 11 • All-cause mortality, Serious adverse events (SAEs) and non-serious adverse events (Non-SAEs) were collected from the start of the study intervention (Day 1) till follow up week 56. All-cause mortality, SAEs and Non-SAEs were reported for the Safety Population which included all randomized participants who received at least 1 dose of study treatment excluding participants from 1 site with GCP violation. AEs were reported treatment-wise.	2.4% 6/250 • Number of events 6 • All-cause mortality, Serious adverse events (SAEs) and non-serious adverse events (Non-SAEs) were collected from the start of the study intervention (Day 1) till follow up week 56. All-cause mortality, SAEs and Non-SAEs were reported for the Safety Population which included all randomized participants who received at least 1 dose of study treatment excluding participants from 1 site with GCP violation. AEs were reported treatment-wise.
Nervous system disorders Headache	7.6% 10/132 • Number of events 13 • All-cause mortality, Serious adverse events (SAEs) and non-serious adverse events (Non-SAEs) were collected from the start of the study intervention (Day 1) till follow up week 56. All-cause mortality, SAEs and Non-SAEs were reported for the Safety Population which included all randomized participants who received at least 1 dose of study treatment excluding participants from 1 site with GCP violation. AEs were reported treatment-wise.	4.8% 12/250 • Number of events 17 • All-cause mortality, Serious adverse events (SAEs) and non-serious adverse events (Non-SAEs) were collected from the start of the study intervention (Day 1) till follow up week 56. All-cause mortality, SAEs and Non-SAEs were reported for the Safety Population which included all randomized participants who received at least 1 dose of study treatment excluding participants from 1 site with GCP violation. AEs were reported treatment-wise.
Respiratory, thoracic and mediastinal disorders Cough	4.5% 6/132 • Number of events 7 • All-cause mortality, Serious adverse events (SAEs) and non-serious adverse events (Non-SAEs) were collected from the start of the study intervention (Day 1) till follow up week 56. All-cause mortality, SAEs and Non-SAEs were reported for the Safety Population which included all randomized participants who received at least 1 dose of study treatment excluding participants from 1 site with GCP violation. AEs were reported treatment-wise.	3.6% 9/250 • Number of events 23 • All-cause mortality, Serious adverse events (SAEs) and non-serious adverse events (Non-SAEs) were collected from the start of the study intervention (Day 1) till follow up week 56. All-cause mortality, SAEs and Non-SAEs were reported for the Safety Population which included all randomized participants who received at least 1 dose of study treatment excluding participants from 1 site with GCP violation. AEs were reported treatment-wise.
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	3.0% 4/132 • Number of events 4 • All-cause mortality, Serious adverse events (SAEs) and non-serious adverse events (Non-SAEs) were collected from the start of the study intervention (Day 1) till follow up week 56. All-cause mortality, SAEs and Non-SAEs were reported for the Safety Population which included all randomized participants who received at least 1 dose of study treatment excluding participants from 1 site with GCP violation. AEs were reported treatment-wise.	4.4% 11/250 • Number of events 15 • All-cause mortality, Serious adverse events (SAEs) and non-serious adverse events (Non-SAEs) were collected from the start of the study intervention (Day 1) till follow up week 56. All-cause mortality, SAEs and Non-SAEs were reported for the Safety Population which included all randomized participants who received at least 1 dose of study treatment excluding participants from 1 site with GCP violation. AEs were reported treatment-wise.
Vascular disorders Hypertension	5.3% 7/132 • Number of events 7 • All-cause mortality, Serious adverse events (SAEs) and non-serious adverse events (Non-SAEs) were collected from the start of the study intervention (Day 1) till follow up week 56. All-cause mortality, SAEs and Non-SAEs were reported for the Safety Population which included all randomized participants who received at least 1 dose of study treatment excluding participants from 1 site with GCP violation. AEs were reported treatment-wise.	3.6% 9/250 • Number of events 10 • All-cause mortality, Serious adverse events (SAEs) and non-serious adverse events (Non-SAEs) were collected from the start of the study intervention (Day 1) till follow up week 56. All-cause mortality, SAEs and Non-SAEs were reported for the Safety Population which included all randomized participants who received at least 1 dose of study treatment excluding participants from 1 site with GCP violation. AEs were reported treatment-wise.