Dose Ranging Study of Amlitelimab in Adult Participants With Moderate-to-severe Asthma

Change From Baseline in Pre-Bronchodilator (BD) Forced Expiratory Volume in One Second (FEV1) at Week 48

The FEV1 was the volume of air exhaled from the lungs in the first second of a forced expiration as measured by spirometer. The pre-BD spirometry was performed after a wash out period of BDs according to their action duration. Baseline was defined as the last available value before the first dose of double-blind study treatment.

Time frame: Baseline (Day 1) and Week 48

Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score at Week 48

The ACQ was a questionnaire that measured the adequacy of asthma control and any changes in asthma control that occurred spontaneously or as a result of treatment. The ACQ-5 had five questions on the asthma symptoms and participants were asked to recall how their asthma had been during the previous week. Each item of the ACQ was measured on a 7-point response scale (0=no impairment, 6=maximum impairment). The ACQ score was the mean of the item responses and ranged from 0 (totally controlled) and 6 (severely uncontrolled). A high score indicated low asthma control. Baseline was defined as the last available value before the first dose of double-blind study treatment.

Time frame: Baseline (Day 1) and Week 48

Change From Baseline in Asthma Quality of Life Questionnaire With Standardized Activities [AQLQ(S)] Self-administered Score at Week 48

The AQLQ(S) was a self-administered participant reported outcome (PRO) to measure the functional impairments that were most troublesome to adolescents and adults \>=12 years of age as a result of their asthma over the past two weeks. The instrument comprised of 32 items, each rated on a 7-point Likert scales from 1 (severely impaired) to 7 (not impaired). The AQLQ(S) had 4 domains: symptoms (12 items), activity limitation (11 items, 5 of which were individualized), emotional function (5 items), and environmental exposure (4 items). The global score was the mean of response to each of the 32 questions and ranged from 1 (severe impairment) to 7 (no impairment). Higher scores indicated better quality of life. Baseline was defined as the last available value before the first dose of double-blind study treatment.

Time frame: Baseline (Day 1) and Week 48

Change From Baseline in Post-Bronchodilator Forced Expiratory Volume in One Second at Week 48

The FEV1 was the volume of air exhaled from the lungs in the first second of a forced expiration as measured by spirometer. The post-BD spirometry was performed within 30 minutes after administration of BD. Baseline was defined as the last available value before the first dose of double-blind study treatment.

Time frame: Baseline (Day 1) and Week 48

Change From Baseline in Pre-Bronchodilator and Post-Bronchodilator Percent Predicted Forced Expiratory Volume in One Second at Week 48

The FEV1 was the volume of air exhaled from the lungs in the first second of a forced expiration as measured by spirometer. The pre-BD spirometry was performed after a wash out period of BDs according to their action duration. The post-BD spirometry was performed within 30 minutes after administration of BD. Baseline was defined as the last available value before the first dose of double-blind study treatment.

Time frame: Baseline (Day 1) and Week 48

Change From Baseline in Asthma Control Questionnaire-5 Score at Weeks 2, 4, 8, 12, 24, 36, and 60

The ACQ was a questionnaire that measured the adequacy of asthma control and any changes in asthma control that occurred spontaneously or as a result of treatment. The ACQ-5 had five questions on the asthma symptoms and participants were asked to recall how their asthma had been during the previous week. Each item of the ACQ was measured on a 7-point response scale (0=no impairment, 6=maximum impairment). The ACQ score was the mean of the item responses and ranged from 0 (totally controlled) and 6 (severely uncontrolled). A high score indicated low asthma control. Baseline was defined as the last available value before the first dose of double-blind study treatment.

Time frame: Baseline (Day 1) and Weeks 2, 4, 8, 12, 24, 36, and 60

Time to First Severe Asthma Exacerbation Event Over 48 Weeks

Time to first severe asthma exacerbation event was defined as the onset date of the first severe asthma exacerbation minus randomization date + 1. Severe asthma exacerbation event was defined as worsening of asthma requiring the use of systemic corticosteroids for \>=3 days or, in the case of a stable maintenance regimen of OCS for the treatment of asthma, a doubling of the dose for 3 or more days, or hospitalization or emergency room visit because of asthma requiring systemic corticosteroids.

Time frame: Baseline (Day 1) to Week 48

Change From Baseline in Pre-Bronchodilator and Post-Bronchodilator Forced Expiratory Volume in One Second at Each Spirometry Timepoint

The FEV1 was the volume of air exhaled from the lungs in the first second of a forced expiration as measured by spirometer. The pre-BD spirometry was performed after a wash out period of BDs according to their action duration. The post-BD spirometry was performed within 30 minutes after administration of BD. Baseline was defined as the last available value before the first dose of double-blind study treatment.

Time frame: Baseline (Day 1) and Weeks 2, 4, 8, 12, 16, 20, 24, 36, and 60 for pre-BD; baseline (Day 1) and Weeks 4, 12, 24, 36, and 60 for post-BD

Change From Baseline in Pre-Bronchodilator and Post-Bronchodilator Peak Expiratory Flow (PEF) at Each Spirometry Timepoint

The PEF was a participant's maximum speed of expiration as measured with a peak flow meter. The pre-BD spirometry was performed after a wash out period of BDs according to their action duration. The post-BD spirometry was performed within 30 minutes after administration of BD. Baseline was defined as the last available value before the first dose of double-blind study treatment.

Time frame: Baseline (Day 1) and Weeks 2, 4, 8, 12, 16, 20, 24, 36, 48, and 60 for pre-BD; baseline (Day 1) and Weeks 4, 12, 24, 36, 48, and 60 for post-BD

Change From Baseline in Pre-Bronchodilator and Post-Bronchodilator Forced Vital Capacity (FVC) at Each Spirometry Timepoint

The FVC was defined as the volume of air that can be forcibly blown out after full inspiration in the upright position as measured by spirometer. The pre-BD spirometry was performed after a wash out period of BDs according to their action duration. The post-BD spirometry was performed within 30 minutes after administration of BD. Baseline was defined as the last available value before the first dose of double-blind study treatment.

Time frame: Baseline (Day 1) and Weeks 2, 4, 8, 12, 16, 20, 24, 36, 48, and 60 for pre-BD; baseline (Day 1) and Weeks 4, 12, 24, 36, 48, and 60 for post-BD

Change From Baseline in Pre-Bronchodilator and Post-Bronchodilator Forced Expiratory Flow (FEF) 25-75% at Each Spirometry Timepoint

The FEF was the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. The FEF 25-75% was defined as the FEF at 25% to 75% of FVC, where FVC was defined as the volume of air that can be forcibly blown out after full inspiration in the upright position. The pre-BD spirometry was performed after a wash out period of BDs according to their action duration. The post-BD spirometry was performed within 30 minutes after administration of BD. Baseline was defined as the last available value before the first dose of double-blind study treatment.

Time frame: Baseline (Day 1) and Weeks 2, 4, 8, 12, 16, 20, 24, 36, 48, and 60 for pre-BD; baseline (Day 1) and Weeks 4, 12, 24, 36, 48, and 60 for post-BD

Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) at Weeks 2, 4, 8, 12, 16, 24, 36, 48, and 60

FeNO was a measure of nitric oxide in exhaled breath produced by epithelial cells in the lung and considered as a biomarker of Type-2 inflammation in asthma. FeNO levels were collected on site with a dedicated medical device. The FeNO test was completed prior to impulse oscillometry and spirometry. Baseline was defined as the last available value before the first dose of double-blind study treatment.

Time frame: Baseline (Day 1) and Weeks 2, 4, 8, 12, 16, 24, 36, 48, and 60

Annualized Rate of Loss of Asthma Control (LOAC) Events Over 48 Weeks

LOAC events were defined by one or several of the following criteria: a 30% or greater reduction from baseline in morning PEF on 2 consecutive days; \>=6 additional reliever puffs of short-acting beta 2-agonists (SABA) or \>=4 additional puffs of low-dose ICS/formoterol in a 24-hour period (compared to baseline) on 2 consecutive days; increase in ICS \>=4 times than the Visit 2 dose; worsening of asthma requiring the use of systemic corticosteroids for \>=3 days or, in the case of a stable maintenance regimen of OCS for the treatment of asthma, a doubling of the dose for 3 or more days; or hospitalization or emergency room visit because of asthma requiring systemic corticosteroids severe exacerbation event. Annualized rate was the total number of severe asthma exacerbation events divided by the total observation duration and was estimated based on negative binomial regression.

Time frame: Baseline (Day 1) to Week 48

Time to First Loss of Asthma Control Event Over 48 Weeks

Time to first LOAC event was defined as the onset date of the first LOAC minus randomization date + 1. LOAC events were defined by one or several of the following criteria: a 30% or greater reduction from baseline in morning PEF on 2 consecutive days; \>=6 additional reliever puffs of SABA or \>=4 additional puffs of low-dose ICS/formoterol in a 24-hour period (compared to baseline) on 2 consecutive days; increase in ICS \>=4 times than the Visit 2 dose; worsening of asthma requiring the use of systemic corticosteroids for \>=3 days or, in the case of a stable maintenance regimen of OCS for the treatment of asthma, a doubling of the dose for 3 or more days; or hospitalization or emergency room visit because of asthma requiring systemic corticosteroids severe exacerbation event.

Time frame: Baseline (Day 1) to Week 48

Change From Baseline in the Asthma Daytime Symptom Diary (ADSD) 6-Item Daily Morning Score and in the Asthma Nighttime Symptom Diary (ANSD) 6-Item Daily Evening Score at Weeks 2, 4, 8, 12, 24, 36, 48, and 60

ADSD and ANSD were PRO measures designed to measure asthma symptoms in adult and adolescent (\>=12 years of age) participants diagnosed with mild-to-severe asthma. Both scales assessed asthma severity based on participant self-report of asthma core symptoms, i.e., difficulty of breathing; wheezing; shortness of breath; chest tightness; chest pain; and cough. Participants were asked to complete ADSD every night before they go to bed, thinking about their asthma symptoms today, from when they got up this morning until now; ANSD when getting up, thinking about their asthma symptoms last night from when they went to bed until now. Both scales consisted 6 items rated using an 11-point numerical rating scale that ranged from 0 (none) to 10 (as bad as you can imagine). Total score was an average of all 6 items for ADSD and ANSD each and therefore ranged from 0 to 10. Higher scores indicated worse outcomes. Baseline: last available value before first dose of double-blind study treatment.

Time frame: Baseline (Day 1) and Weeks 2, 4, 8, 12, 24, 36, 48, and 60

Annualized Rate of Severe Asthma Exacerbations Requiring Hospitalization or Emergency Room or Urgent Care Visit Over 48 Weeks

Severe asthma exacerbation event was defined as worsening of asthma requiring the use of systemic corticosteroids for \>=3 days or, in the case of a stable maintenance regimen of OCS for the treatment of asthma, a doubling of the dose for 3 or more days, or hospitalization or emergency room visit because of asthma requiring systemic corticosteroids. Severe asthma exacerbation events requiring hospitalization or emergency room or urgent care visit during the 48-week treatment period were recorded. Annualized rate was the total number of severe asthma exacerbation events divided by the total observation duration and was estimated based on negative binomial regression.

Time frame: Baseline (Day 1) to Week 48

Change From Baseline in the Numbers of Inhalations Per Day of Short-Acting Beta 2-Agonists or Low-Dose Inhaled Corticosteroid/Formoterol for Symptom Relief at Weeks 2, 4, 8, 12, 24, 36, 48, and 60

Participants were administered SABA or low-dose ICS/formoterol via oral inhalation as reliever medication as needed during the study and the number of inhalations/day were recorded. Baseline was defined as last available value before first dose of double-blind study treatment.

Time frame: Baseline (Day 1) and Weeks 2, 4, 8, 12, 24, 36, 48, and 60

Serum Amlitelimab Concentrations

Blood samples were collected at the specified timepoints for measurement of serum concentrations of amlitelimab.

Time frame: Weeks 4, 8, 12, 16, 24, 36, 48, and 60

Number of Participants With Anti-Drug Antibodies (ADA) to Amlitelimab

Serum samples were collected to evaluate antibodies to amlitelimab. Participants with treatment-emergent ADAs were participants with at least one treatment-induced/boosted ADA. Participants with treatment-induced ADAs were participants with ADAs that developed during the treatment-emergent (TE) period and without pre-existing ADA (including participants without pre-treatment samples). Participants with treatment-boosted ADAs were participants with pre-existing ADAs that were boosted during the TE period to a significant higher titer than the baseline. Number of participants with treatment-emergent ADAs are reported.

Time frame: From first dose of study treatment (Day 1) up to end of study visit (Week 72)

Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Adverse Events of Special Interest (TEAESIs) and Treatment-Emergent Serious Adverse Events (TESAEs)

Adverse event (AE): any untoward medical occurrence in participant or clinical study participant, temporally associated with use of study treatment, whether or not considered related to study treatment. TEAEs: AEs that developed, worsened or became serious during TE period. Serious AE: any untoward medical occurrence that at any dose, met one or more of criteria: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was congenital anomaly/birth defect or was significant medical event that jeopardized the participant or required medical or surgical intervention to prevent one of above outcomes. AESI: AE (serious or non-serious) of scientific and medical concern specific to Sponsor's product or program, for which ongoing monitoring and immediate notification by Investigator to Sponsor was required. Percentages are rounded off to tenth decimal place.

Time frame: From first dose of study treatment (Day 1) up to last dose of study treatment + 168 days, approximately 88 weeks

Change From Baseline in Asthma Quality of Life Questionnaire With Standardized Activities Self-administered Score at Weeks 2, 4, 8, 12, 24, 36, and 60

The AQLQ(S) was a self-administered PRO to measure the functional impairments that were most troublesome to adolescents and adults \>=12 years of age as a result of their asthma over the past two weeks. The instrument comprised of 32 items, each rated on a 7-point Likert scales from 1 to (severely impaired) to 7 (not impaired). The AQLQ(S) had 4 domains: symptoms (12 items), activity limitation (11 items, 5 of which were individualized), emotional function (5 items), and environmental exposure (4 items). The global score was the mean of response to each of the 32 questions and ranged from 1 (severe impairment) to 7 (no impairment). Higher scores indicated better quality of life. Baseline was defined as the last available value before the first dose of double-blind study treatment.

Time frame: Baseline (Day 1) and Weeks 2, 4, 8, 12, 24, 36, and 60

Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score at Weeks 2, 4, 8, 12, 24, 36, 48, and 60

SGRQ was 50-item questionnaire to measure and quantify health status in adult participants with chronic airflow limitation and consisted of three domains: symptoms (8 items \[covered symptomatology, frequency and severity of cough, sputum production, wheeze, breathlessness, duration and frequency of attacks of breathlessness/wheeze\]), activity (16 items \[covered disturbances to participants' daily physical activities\]), impacts (26 items \[covered effects that chest troubles had on participants' daily life and psycho-social functions\]). Global score was calculated by summing all positive responses in questionnaire and expressing result as percentage of total weight for questionnaire. Global and domain scores ranged from 0 to 100 with 100=worst possible health status and 0=best possible health status. Higher score=worse health status/heath related quality of life. Baseline: last available value before first dose of double-blind study treatment.

Time frame: Baseline (Day 1) and Weeks 2, 4, 8, 12, 24, 36, 48, and 60

Percentage of Participants With a Decrease From Baseline of at Least 4 Points in St. George's Respiratory Questionnaire Total Score at Week 48

SGRQ was 50-item questionnaire to measure and quantify health status in adult participants with chronic airflow limitation and consisted of three domains: symptoms (8 items\[covered symptomatology, frequency and severity of cough, sputum production, wheeze, breathlessness, duration and frequency of attacks of breathlessness/wheeze\]), activity (16 items\[covered disturbances to participants' daily physical activities\]), impacts (26 items\[covered effects that chest troubles had on participants' daily life and psycho-social functions\]). Global score was calculated by summing all positive responses in questionnaire and expressing result as percentage of total weight for questionnaire. Global and domain scores ranged from 0 to 100; 100=worst possible health status and 0=best possible health status. Higher score=worse health status/heath related quality of life. Baseline:last available value before first dose of double-blind study treatment. Percentages are rounded off to tenth decimal place.

Time frame: Baseline (Day 1) to Week 48

Change From Baseline in Asthma Control Questionnaire-6 (ACQ-6) and Asthma Control Questionnaire-7 Scores at Weeks 2, 4, 8, 12, 24, 36, 48, and 60

The ACQ was a questionnaire that measured the adequacy of asthma control and any changes in asthma control that occurred spontaneously or as a result of treatment. The ACQ-5 had five questions on the asthma symptoms and participants were asked to recall how their asthma had been during the previous week. The ACQ-6 included an additional item that scored the average number of daily puffs needed from a SABA BD during the past week and the ACQ-7 included this SABA item, plus a final clinic-assessed item scoring FEV1% predicted. Each item of the ACQ was measured on a 7-point response scale (0=no impairment, 6=maximum impairment). The ACQ-6 and ACQ-7 scores were the mean of the item responses in the respective scales and ranged from 0 (totally controlled) and 6 (severely uncontrolled). A high score indicated low asthma control. Baseline was defined as the last available value before the first dose of double-blind study treatment.

Time frame: Baseline (Day 1) and Weeks 2, 4, 8, 12, 24, 36, 48, and 60