Trial Outcomes & Findings for Dupilumab in CRSsNP (NCT NCT04678856)

Last Updated: 2025-02-10

Results Overview

The CT scan LMK staging system represented the most widely established method of sinus CT scoring. The LMK total score is based on assessment of the CT scan findings for each sinus area (maxillary, anterior ethmoid, posterior ethmoid, sphenoid, and frontal sinus on each side). The extent of mucosal opacification is rated on a 3-point scale ranging from 0 = normal to 2 = total opacification. In addition, the ostiomeatal complex is graded as 0 = not occluded or 2 = occluded. The maximum score is therefore 12 per side; total score ranges from 0 (normal) to 24 (more opacified), corresponding to the sum of all sinuses and the ostiomeatal unit. Higher score indicated worse outcome. Baseline was defined as the last available value up to randomization date and prior to the first dose of study medication.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

71 participants

Primary outcome timeframe

Baseline (Day 1) and Week 24

Results posted on

2025-02-10

Participant Flow

The study was conducted at 57 centers in 13 countries. A total of 269 participants were screened between 02 December 2020 to 26 April 2023, of which 198 participants were screen failures. Screen failures were mainly due to not meeting the eligibility criteria.

A total of 71 participants were randomized in a ratio of 1:1 to receive dupilumab or matching placebo. Randomization was stratified by screening blood eosinophil count (≥300 cells per cubic millimeter \[/mm\^3\] or \<300 cells/mm\^3), background intranasal corticosteroids (INCS) use (yes or no), and region.

Participant milestones

Participant milestones
Measure	Placebo Participants received matching placebo via subcutaneous (SC) injection every 2 weeks (q2w) for up to 53.2 weeks.	Dupilumab 300 mg q2w Participants received dupilumab 300 milligrams (mg) via SC injection q2w for up to 53.1 weeks.
Overall Study STARTED	33	38
Overall Study COMPLETED	25	37
Overall Study NOT COMPLETED	8	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received matching placebo via subcutaneous (SC) injection every 2 weeks (q2w) for up to 53.2 weeks.	Dupilumab 300 mg q2w Participants received dupilumab 300 milligrams (mg) via SC injection q2w for up to 53.1 weeks.
Overall Study Not related to Coronavirus Disease-2019 (COVID-19)	3	0
Overall Study Withdrawal by Subject	5	1

Baseline Characteristics

Dupilumab in CRSsNP

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=33 Participants Participants received matching placebo via SC injection q2w for up to 53.2 weeks.	Dupilumab 300 mg q2w n=38 Participants Participants received dupilumab 300 mg via SC injection q2w for up to 53.1 weeks.	Total n=71 Participants Total of all reporting groups
Age, Continuous	47.45 Years STANDARD_DEVIATION 17.46 • n=5 Participants	46.45 Years STANDARD_DEVIATION 12.60 • n=7 Participants	46.92 Years STANDARD_DEVIATION 14.95 • n=5 Participants
Sex: Female, Male Female	16 Participants n=5 Participants	25 Participants n=7 Participants	41 Participants n=5 Participants
Sex: Female, Male Male	17 Participants n=5 Participants	13 Participants n=7 Participants	30 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	30 Participants n=5 Participants	31 Participants n=7 Participants	61 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Lund-Mackay (LMK) Score	11.50 Score on a scale STANDARD_DEVIATION 3.19 • n=5 Participants	11.41 Score on a scale STANDARD_DEVIATION 3.69 • n=7 Participants	11.45 Score on a scale STANDARD_DEVIATION 3.44 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1) and Week 24

Population: Intent-to-treat (ITT) population with screening blood eosinophil count ≥300 cells/mm\^3 included all randomized participants with screening blood eosinophil count ≥300 cells/mm\^3 analyzed according to the treatment group allocated by randomization regardless if treatment kit was used or not.

Outcome measures

Outcome measures
Measure	Dupilumab 300 mg q2w n=16 Participants Participants received dupilumab 300 mg via SC injection q2w for up to 53.1 weeks.	Dupilumab 300 mg q2w Participants received dupilumab 300 mg via SC injection q2w for up to 53.1 weeks.
Change From Baseline to Week 24 in Opacification of Sinuses Assessed by Computed Tomography (CT) Scan Using the Lund Mackay (LMK) Score in Dupilumab Group	-6.63 Score on a scale Standard Deviation 3.91	—

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 24

Population: ITT population with screening blood eosinophil count ≥300 cells/mm\^3 included all randomized participants with screening blood eosinophil count ≥300 cells/mm\^3 analyzed according to the treatment group allocated by randomization regardless if treatment kit was used or not. Only those participants with data collected at Week 24 are reported.

Outcome measures

Outcome measures
Measure	Dupilumab 300 mg q2w n=14 Participants Participants received dupilumab 300 mg via SC injection q2w for up to 53.1 weeks.	Dupilumab 300 mg q2w n=16 Participants Participants received dupilumab 300 mg via SC injection q2w for up to 53.1 weeks.
Change From Baseline to Week 24 in Opacification of Sinuses Assessed by CT Scan Using the LMK Score	-0.68 Score on a scale Standard Deviation 2.26	-6.63 Score on a scale Standard Deviation 3.91

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 24

The sTSS is a composite score derived from the following individual items: nasal congestion (NC), anterior/posterior rhinorrhea, and facial pain/pressure. Each of the individual items were scored from 0 (no symptoms) to 3 (severe symptoms). The total score ranges from 0 to 9 and consists of the sum of NC, the averaged rhinorrhea item scores, and facial pain/pressure scores. Higher scores on sTSS indicated greater overall symptom severity. Baseline was defined as the last available value up to randomization date and prior to the first dose of study medication.

Outcome measures

Outcome measures
Measure	Dupilumab 300 mg q2w n=14 Participants Participants received dupilumab 300 mg via SC injection q2w for up to 53.1 weeks.	Dupilumab 300 mg q2w n=16 Participants Participants received dupilumab 300 mg via SC injection q2w for up to 53.1 weeks.
Change From Baseline to Week 24 in Sinus Total Symptom Score (sTSS)	-1.75 Score on a scale Standard Deviation 2.19	-3.18 Score on a scale Standard Deviation 2.68

SECONDARY outcome

Timeframe: From the first dose of study drug (Day 1) up to the last dose of study drug administration (373 days) + 98 days, up to 471 days

Population: Safety population included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.

An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were AEs that developed, worsened or became serious during the treatment-emergent period. A SAE was defined as any untoward medical occurrence that, at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, was a congenital anomaly/birth defect, was a medically important event.

Outcome measures

Outcome measures
Measure	Dupilumab 300 mg q2w n=33 Participants Participants received dupilumab 300 mg via SC injection q2w for up to 53.1 weeks.	Dupilumab 300 mg q2w n=38 Participants Participants received dupilumab 300 mg via SC injection q2w for up to 53.1 weeks.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious AEs (TESAEs), and TEAEs Leading to Treatment Discontinuation TEAEs leading to treatment discontinuation	0 Participants	1 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious AEs (TESAEs), and TEAEs Leading to Treatment Discontinuation TEAEs	27 Participants	29 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious AEs (TESAEs), and TEAEs Leading to Treatment Discontinuation TESAEs	6 Participants	3 Participants

SECONDARY outcome

Timeframe: Baseline (Day 1) and Weeks 12, 24 and 52

Population: Pharmacokinetic (PK) population included all participants in the safety population with at least 1 non-missing result for functional dupilumab concentration in serum after the first dose of the study intervention. Only those participants with data collected at specified timepoints are reported.

Blood samples were collected at the specified timepoints to evaluate serum concentration of dupilumab.

Outcome measures

Outcome measures
Measure	Dupilumab 300 mg q2w n=28 Participants Participants received dupilumab 300 mg via SC injection q2w for up to 53.1 weeks.	Dupilumab 300 mg q2w Participants received dupilumab 300 mg via SC injection q2w for up to 53.1 weeks.
Serum Concentration of Dupilumab Over Time Baseline	0.00 Nanograms per milliliter Standard Deviation 0.00	—
Serum Concentration of Dupilumab Over Time Week 24	62192.86 Nanograms per milliliter Standard Deviation 23979.23	—
Serum Concentration of Dupilumab Over Time Week 52	68365.00 Nanograms per milliliter Standard Deviation 30613.86	—
Serum Concentration of Dupilumab Over Time Week 12	54733.20 Nanograms per milliliter Standard Deviation 26222.53	—

SECONDARY outcome

Timeframe: Baseline (Day 1) and up to Week 52

Population: ADA population included all participants in the safety population who had at least 1 non-missing result in the ADA assay after the first dose of the study intervention.

Plasma samples were collected to evaluate antibodies to dupilumab. Pre-existing immunoreactivity was defined as an ADA positive response in the assay at baseline with all post first dose ADA results negative, OR an ADA positive response at baseline with all post first dose ADA responses less than 4-fold over baseline titer levels. Treatment-emergent ADA responses were defined as a positive response in the ADA assay post first dose, when baseline results were negative or missing. Treatment-boosted response was defined as an ADA positive response in the assay post first dose that was greater-than or equal to 4-fold over baseline titer levels, when baseline results were positive. Samples positive in the ADA assay were further characterized for the presence of NAbs.

Outcome measures

Outcome measures
Measure	Dupilumab 300 mg q2w n=33 Participants Participants received dupilumab 300 mg via SC injection q2w for up to 53.1 weeks.	Dupilumab 300 mg q2w n=38 Participants Participants received dupilumab 300 mg via SC injection q2w for up to 53.1 weeks.
Number of Participants With Antidrug Antibody (ADA) Response to Dupilumab and Positive Neutralizing Antibody (Nab) Pre-existing immunoreactivity	1 Participants	0 Participants
Number of Participants With Antidrug Antibody (ADA) Response to Dupilumab and Positive Neutralizing Antibody (Nab) Treatment-emergent ADA response	1 Participants	1 Participants
Number of Participants With Antidrug Antibody (ADA) Response to Dupilumab and Positive Neutralizing Antibody (Nab) Treatment-boosted ADA response	1 Participants	0 Participants
Number of Participants With Antidrug Antibody (ADA) Response to Dupilumab and Positive Neutralizing Antibody (Nab) Positive Nab	3 Participants	1 Participants

Adverse Events

Placebo

Serious events: 6 serious events

Other events: 12 other events

Deaths: 0 deaths

Dupilumab 300 mg q2w

Serious events: 3 serious events

Other events: 20 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=33 participants at risk Participants received matching placebo via SC injection q2w for up to 53.2 weeks.	Dupilumab 300 mg q2w n=38 participants at risk Participants received dupilumab 300 mg via SC injection q2w for up to 53.1 weeks.
Congenital, familial and genetic disorders Myocardial Bridging	0.00% 0/33 • TEAEs and TESAEs were collected from the first dose of study drug (Day 1) up to the last dose of study drug administration (373 days) + 98 days, up to 471 days. All-cause mortality (deaths) were collected from participant's screening (Day -28) to the end of follow-up for each participant, up to 476 days. Analysis was performed on safety population.	2.6% 1/38 • Number of events 1 • TEAEs and TESAEs were collected from the first dose of study drug (Day 1) up to the last dose of study drug administration (373 days) + 98 days, up to 471 days. All-cause mortality (deaths) were collected from participant's screening (Day -28) to the end of follow-up for each participant, up to 476 days. Analysis was performed on safety population.
Gastrointestinal disorders Chronic Gastritis	0.00% 0/33 • TEAEs and TESAEs were collected from the first dose of study drug (Day 1) up to the last dose of study drug administration (373 days) + 98 days, up to 471 days. All-cause mortality (deaths) were collected from participant's screening (Day -28) to the end of follow-up for each participant, up to 476 days. Analysis was performed on safety population.	2.6% 1/38 • Number of events 1 • TEAEs and TESAEs were collected from the first dose of study drug (Day 1) up to the last dose of study drug administration (373 days) + 98 days, up to 471 days. All-cause mortality (deaths) were collected from participant's screening (Day -28) to the end of follow-up for each participant, up to 476 days. Analysis was performed on safety population.
Hepatobiliary disorders Biloma	0.00% 0/33 • TEAEs and TESAEs were collected from the first dose of study drug (Day 1) up to the last dose of study drug administration (373 days) + 98 days, up to 471 days. All-cause mortality (deaths) were collected from participant's screening (Day -28) to the end of follow-up for each participant, up to 476 days. Analysis was performed on safety population.	2.6% 1/38 • Number of events 1 • TEAEs and TESAEs were collected from the first dose of study drug (Day 1) up to the last dose of study drug administration (373 days) + 98 days, up to 471 days. All-cause mortality (deaths) were collected from participant's screening (Day -28) to the end of follow-up for each participant, up to 476 days. Analysis was performed on safety population.
Hepatobiliary disorders Cholecystitis Acute	0.00% 0/33 • TEAEs and TESAEs were collected from the first dose of study drug (Day 1) up to the last dose of study drug administration (373 days) + 98 days, up to 471 days. All-cause mortality (deaths) were collected from participant's screening (Day -28) to the end of follow-up for each participant, up to 476 days. Analysis was performed on safety population.	2.6% 1/38 • Number of events 1 • TEAEs and TESAEs were collected from the first dose of study drug (Day 1) up to the last dose of study drug administration (373 days) + 98 days, up to 471 days. All-cause mortality (deaths) were collected from participant's screening (Day -28) to the end of follow-up for each participant, up to 476 days. Analysis was performed on safety population.
Infections and infestations Chronic Sinusitis	3.0% 1/33 • Number of events 1 • TEAEs and TESAEs were collected from the first dose of study drug (Day 1) up to the last dose of study drug administration (373 days) + 98 days, up to 471 days. All-cause mortality (deaths) were collected from participant's screening (Day -28) to the end of follow-up for each participant, up to 476 days. Analysis was performed on safety population.	0.00% 0/38 • TEAEs and TESAEs were collected from the first dose of study drug (Day 1) up to the last dose of study drug administration (373 days) + 98 days, up to 471 days. All-cause mortality (deaths) were collected from participant's screening (Day -28) to the end of follow-up for each participant, up to 476 days. Analysis was performed on safety population.
Musculoskeletal and connective tissue disorders Foot Deformity	3.0% 1/33 • Number of events 1 • TEAEs and TESAEs were collected from the first dose of study drug (Day 1) up to the last dose of study drug administration (373 days) + 98 days, up to 471 days. All-cause mortality (deaths) were collected from participant's screening (Day -28) to the end of follow-up for each participant, up to 476 days. Analysis was performed on safety population.	0.00% 0/38 • TEAEs and TESAEs were collected from the first dose of study drug (Day 1) up to the last dose of study drug administration (373 days) + 98 days, up to 471 days. All-cause mortality (deaths) were collected from participant's screening (Day -28) to the end of follow-up for each participant, up to 476 days. Analysis was performed on safety population.
Musculoskeletal and connective tissue disorders Spinal Osteoarthritis	3.0% 1/33 • Number of events 1 • TEAEs and TESAEs were collected from the first dose of study drug (Day 1) up to the last dose of study drug administration (373 days) + 98 days, up to 471 days. All-cause mortality (deaths) were collected from participant's screening (Day -28) to the end of follow-up for each participant, up to 476 days. Analysis was performed on safety population.	0.00% 0/38 • TEAEs and TESAEs were collected from the first dose of study drug (Day 1) up to the last dose of study drug administration (373 days) + 98 days, up to 471 days. All-cause mortality (deaths) were collected from participant's screening (Day -28) to the end of follow-up for each participant, up to 476 days. Analysis was performed on safety population.
Nervous system disorders Diabetic Neuropathy	3.0% 1/33 • Number of events 2 • TEAEs and TESAEs were collected from the first dose of study drug (Day 1) up to the last dose of study drug administration (373 days) + 98 days, up to 471 days. All-cause mortality (deaths) were collected from participant's screening (Day -28) to the end of follow-up for each participant, up to 476 days. Analysis was performed on safety population.	0.00% 0/38 • TEAEs and TESAEs were collected from the first dose of study drug (Day 1) up to the last dose of study drug administration (373 days) + 98 days, up to 471 days. All-cause mortality (deaths) were collected from participant's screening (Day -28) to the end of follow-up for each participant, up to 476 days. Analysis was performed on safety population.
Nervous system disorders Syncope	3.0% 1/33 • Number of events 1 • TEAEs and TESAEs were collected from the first dose of study drug (Day 1) up to the last dose of study drug administration (373 days) + 98 days, up to 471 days. All-cause mortality (deaths) were collected from participant's screening (Day -28) to the end of follow-up for each participant, up to 476 days. Analysis was performed on safety population.	0.00% 0/38 • TEAEs and TESAEs were collected from the first dose of study drug (Day 1) up to the last dose of study drug administration (373 days) + 98 days, up to 471 days. All-cause mortality (deaths) were collected from participant's screening (Day -28) to the end of follow-up for each participant, up to 476 days. Analysis was performed on safety population.
Respiratory, thoracic and mediastinal disorders Asthma	3.0% 1/33 • Number of events 1 • TEAEs and TESAEs were collected from the first dose of study drug (Day 1) up to the last dose of study drug administration (373 days) + 98 days, up to 471 days. All-cause mortality (deaths) were collected from participant's screening (Day -28) to the end of follow-up for each participant, up to 476 days. Analysis was performed on safety population.	0.00% 0/38 • TEAEs and TESAEs were collected from the first dose of study drug (Day 1) up to the last dose of study drug administration (373 days) + 98 days, up to 471 days. All-cause mortality (deaths) were collected from participant's screening (Day -28) to the end of follow-up for each participant, up to 476 days. Analysis was performed on safety population.
Vascular disorders Peripheral Arterial Occlusive Disease	3.0% 1/33 • Number of events 2 • TEAEs and TESAEs were collected from the first dose of study drug (Day 1) up to the last dose of study drug administration (373 days) + 98 days, up to 471 days. All-cause mortality (deaths) were collected from participant's screening (Day -28) to the end of follow-up for each participant, up to 476 days. Analysis was performed on safety population.	0.00% 0/38 • TEAEs and TESAEs were collected from the first dose of study drug (Day 1) up to the last dose of study drug administration (373 days) + 98 days, up to 471 days. All-cause mortality (deaths) were collected from participant's screening (Day -28) to the end of follow-up for each participant, up to 476 days. Analysis was performed on safety population.

Other adverse events

Additional Information

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Results disclosure agreements

Principal investigator is a sponsor employee The Sponsor supports publication of clinical trial results but may request that investigators temporarily delay or alter publications in order to protect proprietary information. The Sponsor may also require that the results of multicenter studies be published only in their entirety and not as individual site data.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=33 participants at risk Participants received matching placebo via SC injection q2w for up to 53.2 weeks.	Dupilumab 300 mg q2w n=38 participants at risk Participants received dupilumab 300 mg via SC injection q2w for up to 53.1 weeks.
Gastrointestinal disorders Gastrooesophageal Reflux Disease	0.00% 0/33 • TEAEs and TESAEs were collected from the first dose of study drug (Day 1) up to the last dose of study drug administration (373 days) + 98 days, up to 471 days. All-cause mortality (deaths) were collected from participant's screening (Day -28) to the end of follow-up for each participant, up to 476 days. Analysis was performed on safety population.	5.3% 2/38 • Number of events 2 • TEAEs and TESAEs were collected from the first dose of study drug (Day 1) up to the last dose of study drug administration (373 days) + 98 days, up to 471 days. All-cause mortality (deaths) were collected from participant's screening (Day -28) to the end of follow-up for each participant, up to 476 days. Analysis was performed on safety population.
General disorders Fatigue	0.00% 0/33 • TEAEs and TESAEs were collected from the first dose of study drug (Day 1) up to the last dose of study drug administration (373 days) + 98 days, up to 471 days. All-cause mortality (deaths) were collected from participant's screening (Day -28) to the end of follow-up for each participant, up to 476 days. Analysis was performed on safety population.	5.3% 2/38 • Number of events 3 • TEAEs and TESAEs were collected from the first dose of study drug (Day 1) up to the last dose of study drug administration (373 days) + 98 days, up to 471 days. All-cause mortality (deaths) were collected from participant's screening (Day -28) to the end of follow-up for each participant, up to 476 days. Analysis was performed on safety population.
General disorders Injection Site Erythema	3.0% 1/33 • Number of events 20 • TEAEs and TESAEs were collected from the first dose of study drug (Day 1) up to the last dose of study drug administration (373 days) + 98 days, up to 471 days. All-cause mortality (deaths) were collected from participant's screening (Day -28) to the end of follow-up for each participant, up to 476 days. Analysis was performed on safety population.	10.5% 4/38 • Number of events 9 • TEAEs and TESAEs were collected from the first dose of study drug (Day 1) up to the last dose of study drug administration (373 days) + 98 days, up to 471 days. All-cause mortality (deaths) were collected from participant's screening (Day -28) to the end of follow-up for each participant, up to 476 days. Analysis was performed on safety population.
General disorders Injection Site Reaction	3.0% 1/33 • Number of events 8 • TEAEs and TESAEs were collected from the first dose of study drug (Day 1) up to the last dose of study drug administration (373 days) + 98 days, up to 471 days. All-cause mortality (deaths) were collected from participant's screening (Day -28) to the end of follow-up for each participant, up to 476 days. Analysis was performed on safety population.	7.9% 3/38 • Number of events 12 • TEAEs and TESAEs were collected from the first dose of study drug (Day 1) up to the last dose of study drug administration (373 days) + 98 days, up to 471 days. All-cause mortality (deaths) were collected from participant's screening (Day -28) to the end of follow-up for each participant, up to 476 days. Analysis was performed on safety population.
General disorders Injection Site Swelling	6.1% 2/33 • Number of events 23 • TEAEs and TESAEs were collected from the first dose of study drug (Day 1) up to the last dose of study drug administration (373 days) + 98 days, up to 471 days. All-cause mortality (deaths) were collected from participant's screening (Day -28) to the end of follow-up for each participant, up to 476 days. Analysis was performed on safety population.	0.00% 0/38 • TEAEs and TESAEs were collected from the first dose of study drug (Day 1) up to the last dose of study drug administration (373 days) + 98 days, up to 471 days. All-cause mortality (deaths) were collected from participant's screening (Day -28) to the end of follow-up for each participant, up to 476 days. Analysis was performed on safety population.
Infections and infestations Bronchitis	0.00% 0/33 • TEAEs and TESAEs were collected from the first dose of study drug (Day 1) up to the last dose of study drug administration (373 days) + 98 days, up to 471 days. All-cause mortality (deaths) were collected from participant's screening (Day -28) to the end of follow-up for each participant, up to 476 days. Analysis was performed on safety population.	5.3% 2/38 • Number of events 2 • TEAEs and TESAEs were collected from the first dose of study drug (Day 1) up to the last dose of study drug administration (373 days) + 98 days, up to 471 days. All-cause mortality (deaths) were collected from participant's screening (Day -28) to the end of follow-up for each participant, up to 476 days. Analysis was performed on safety population.
Infections and infestations Covid-19	21.2% 7/33 • Number of events 8 • TEAEs and TESAEs were collected from the first dose of study drug (Day 1) up to the last dose of study drug administration (373 days) + 98 days, up to 471 days. All-cause mortality (deaths) were collected from participant's screening (Day -28) to the end of follow-up for each participant, up to 476 days. Analysis was performed on safety population.	21.1% 8/38 • Number of events 9 • TEAEs and TESAEs were collected from the first dose of study drug (Day 1) up to the last dose of study drug administration (373 days) + 98 days, up to 471 days. All-cause mortality (deaths) were collected from participant's screening (Day -28) to the end of follow-up for each participant, up to 476 days. Analysis was performed on safety population.
Infections and infestations Gastroenteritis	0.00% 0/33 • TEAEs and TESAEs were collected from the first dose of study drug (Day 1) up to the last dose of study drug administration (373 days) + 98 days, up to 471 days. All-cause mortality (deaths) were collected from participant's screening (Day -28) to the end of follow-up for each participant, up to 476 days. Analysis was performed on safety population.	5.3% 2/38 • Number of events 3 • TEAEs and TESAEs were collected from the first dose of study drug (Day 1) up to the last dose of study drug administration (373 days) + 98 days, up to 471 days. All-cause mortality (deaths) were collected from participant's screening (Day -28) to the end of follow-up for each participant, up to 476 days. Analysis was performed on safety population.
Infections and infestations Nasopharyngitis	6.1% 2/33 • Number of events 2 • TEAEs and TESAEs were collected from the first dose of study drug (Day 1) up to the last dose of study drug administration (373 days) + 98 days, up to 471 days. All-cause mortality (deaths) were collected from participant's screening (Day -28) to the end of follow-up for each participant, up to 476 days. Analysis was performed on safety population.	5.3% 2/38 • Number of events 3 • TEAEs and TESAEs were collected from the first dose of study drug (Day 1) up to the last dose of study drug administration (373 days) + 98 days, up to 471 days. All-cause mortality (deaths) were collected from participant's screening (Day -28) to the end of follow-up for each participant, up to 476 days. Analysis was performed on safety population.
Infections and infestations Otitis Media	3.0% 1/33 • Number of events 1 • TEAEs and TESAEs were collected from the first dose of study drug (Day 1) up to the last dose of study drug administration (373 days) + 98 days, up to 471 days. All-cause mortality (deaths) were collected from participant's screening (Day -28) to the end of follow-up for each participant, up to 476 days. Analysis was performed on safety population.	5.3% 2/38 • Number of events 2 • TEAEs and TESAEs were collected from the first dose of study drug (Day 1) up to the last dose of study drug administration (373 days) + 98 days, up to 471 days. All-cause mortality (deaths) were collected from participant's screening (Day -28) to the end of follow-up for each participant, up to 476 days. Analysis was performed on safety population.
Infections and infestations Upper Respiratory Tract Infection	9.1% 3/33 • Number of events 3 • TEAEs and TESAEs were collected from the first dose of study drug (Day 1) up to the last dose of study drug administration (373 days) + 98 days, up to 471 days. All-cause mortality (deaths) were collected from participant's screening (Day -28) to the end of follow-up for each participant, up to 476 days. Analysis was performed on safety population.	0.00% 0/38 • TEAEs and TESAEs were collected from the first dose of study drug (Day 1) up to the last dose of study drug administration (373 days) + 98 days, up to 471 days. All-cause mortality (deaths) were collected from participant's screening (Day -28) to the end of follow-up for each participant, up to 476 days. Analysis was performed on safety population.
Infections and infestations Viral Upper Respiratory Tract Infection	6.1% 2/33 • Number of events 2 • TEAEs and TESAEs were collected from the first dose of study drug (Day 1) up to the last dose of study drug administration (373 days) + 98 days, up to 471 days. All-cause mortality (deaths) were collected from participant's screening (Day -28) to the end of follow-up for each participant, up to 476 days. Analysis was performed on safety population.	5.3% 2/38 • Number of events 2 • TEAEs and TESAEs were collected from the first dose of study drug (Day 1) up to the last dose of study drug administration (373 days) + 98 days, up to 471 days. All-cause mortality (deaths) were collected from participant's screening (Day -28) to the end of follow-up for each participant, up to 476 days. Analysis was performed on safety population.
Injury, poisoning and procedural complications Accidental Overdose	9.1% 3/33 • Number of events 3 • TEAEs and TESAEs were collected from the first dose of study drug (Day 1) up to the last dose of study drug administration (373 days) + 98 days, up to 471 days. All-cause mortality (deaths) were collected from participant's screening (Day -28) to the end of follow-up for each participant, up to 476 days. Analysis was performed on safety population.	5.3% 2/38 • Number of events 2 • TEAEs and TESAEs were collected from the first dose of study drug (Day 1) up to the last dose of study drug administration (373 days) + 98 days, up to 471 days. All-cause mortality (deaths) were collected from participant's screening (Day -28) to the end of follow-up for each participant, up to 476 days. Analysis was performed on safety population.
Injury, poisoning and procedural complications Fall	6.1% 2/33 • Number of events 2 • TEAEs and TESAEs were collected from the first dose of study drug (Day 1) up to the last dose of study drug administration (373 days) + 98 days, up to 471 days. All-cause mortality (deaths) were collected from participant's screening (Day -28) to the end of follow-up for each participant, up to 476 days. Analysis was performed on safety population.	2.6% 1/38 • Number of events 1 • TEAEs and TESAEs were collected from the first dose of study drug (Day 1) up to the last dose of study drug administration (373 days) + 98 days, up to 471 days. All-cause mortality (deaths) were collected from participant's screening (Day -28) to the end of follow-up for each participant, up to 476 days. Analysis was performed on safety population.
Musculoskeletal and connective tissue disorders Arthralgia	3.0% 1/33 • Number of events 1 • TEAEs and TESAEs were collected from the first dose of study drug (Day 1) up to the last dose of study drug administration (373 days) + 98 days, up to 471 days. All-cause mortality (deaths) were collected from participant's screening (Day -28) to the end of follow-up for each participant, up to 476 days. Analysis was performed on safety population.	5.3% 2/38 • Number of events 2 • TEAEs and TESAEs were collected from the first dose of study drug (Day 1) up to the last dose of study drug administration (373 days) + 98 days, up to 471 days. All-cause mortality (deaths) were collected from participant's screening (Day -28) to the end of follow-up for each participant, up to 476 days. Analysis was performed on safety population.
Musculoskeletal and connective tissue disorders Back Pain	0.00% 0/33 • TEAEs and TESAEs were collected from the first dose of study drug (Day 1) up to the last dose of study drug administration (373 days) + 98 days, up to 471 days. All-cause mortality (deaths) were collected from participant's screening (Day -28) to the end of follow-up for each participant, up to 476 days. Analysis was performed on safety population.	5.3% 2/38 • Number of events 3 • TEAEs and TESAEs were collected from the first dose of study drug (Day 1) up to the last dose of study drug administration (373 days) + 98 days, up to 471 days. All-cause mortality (deaths) were collected from participant's screening (Day -28) to the end of follow-up for each participant, up to 476 days. Analysis was performed on safety population.
Nervous system disorders Headache	6.1% 2/33 • Number of events 2 • TEAEs and TESAEs were collected from the first dose of study drug (Day 1) up to the last dose of study drug administration (373 days) + 98 days, up to 471 days. All-cause mortality (deaths) were collected from participant's screening (Day -28) to the end of follow-up for each participant, up to 476 days. Analysis was performed on safety population.	5.3% 2/38 • Number of events 2 • TEAEs and TESAEs were collected from the first dose of study drug (Day 1) up to the last dose of study drug administration (373 days) + 98 days, up to 471 days. All-cause mortality (deaths) were collected from participant's screening (Day -28) to the end of follow-up for each participant, up to 476 days. Analysis was performed on safety population.