Dose ranging study of amlitelimab in adult participants with moderate-to-severe asthma

JRCT ID: jRCT2031220538

Registered date:25/12/2022

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Asthma
• Date of first enrollment: 04/01/2023
• Target sample size: 420
• Countries of recruitment: Argentina,Japan,Canada,Japan,Chile,Japan,Italy,Japan,Republic of Korea,Japan,South Africa,Japan,United Kingdom,Japan,United States,Japan,Brazil,Japan,Hungary,Japan,Mexico,Japan,Poland,Japan,Turkey,Japan
• Study type: Interventional

Intervention(s)

Drug: Amlitelimab
Injection solution Subcutaneous injection
Drug: Placebo
Injection solution Subcutaneous injection

Outcome(s)

Primary Outcome

1.Annualized rate of severe exacerbation events over 48 weeks
[Time Frame baseline:Baseline through Week 48]
Severe exacerbation events are defined as: worsening of asthma requiring the use of systemic corticosteroids for >=3 days or, in the case of a stable maintenance regimen of oral corticosteroids 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.

Secondary Outcome

1.Change from baseline in pre-bronchodilator (BD) FEV1 at Week 48
[Time Frame baseline:Baseline to Week 48]
2.Change from baseline in Asthma Control Questionnaire 5 (ACQ-5) score at Week 48
[Time Frame baseline:Baseline to Week 48]
The ACQ-5 has five questions on the asthma symptoms. The score ranges from 0 (totally controlled) and 6 (severely uncontrolled). A high score indicates low asthma control.
3.Change from baseline in Asthma Quality of Life
Questionnaire with Standardized Activities (AQLQ (S)) Self-Administered Score at Week 48
[Time Frame baseline:Baseline to Week 48]
The AQLQ(S) is designed as a self-administered participant reported outcome to measure the functional impairments. The overall score is 1 to 7. Higher AQLQ scores indicate better health-related quality of life.
4.Change from baseline in post-BD FEV1 at Week 48
[Time Frame baseline:Baseline to Week 48]
5.The absolute change in the percent predicted FEV1 from baseline to Week 48 (pre-BD and post-BD)
[Time Frame baseline:Baseline to Week 48]
6.Change from baseline in ACQ-5 score at Weeks 2, 4, 8, 12, 24, 36, and 60
[Time Frame baseline:Baseline to Weeks 2, 4, 8, 12, 24, 36, and 60]
The ACQ-5 has five questions on the asthma symptoms. The score ranges from 0 (totally controlled) and 6 (severely uncontrolled). A high score indicates low asthma control.
7.Time to first severe exacerbation event
[Time Frame baseline:Baseline through Week 48]
Severe exacerbation events are defined as: worsening of asthma requiring the use of systemic corticosteroids for >=3 days or, in the case of a stable maintenance regimen of oral corticosteroids 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.
8.Change from baseline in pre-BD and post-BD FEV1
[Time Frame baseline:Baseline to Weeks 2, 4, 8, 12,16, 24, 36 and 60]
9.Change from baseline in peak expiratory flow (PEF) and forced expiratory flow (FEF) 25-75%
[Time Frame baseline:Baseline to Weeks 4, 12, 24, 36, 48 and 60]
10.Change from baseline in forced vital capacity (FVC)
[Time Frame baseline:Baseline to Weeks 4, 12, 24, 36, 48 and 60]
11.Change from baseline in FeNO at Weeks 2, 4, 8, 12, 16, 24, 36, 48 and 60
[Time Frame baseline:Baseline to Weeks 2, 4, 8, 12, 16, 24, 36, 48 and 60]
12.Annualized rate of loss of asthma control (LOAC) events during 48 weeks of treatment
[Time Frame baseline:Baseline through Week 48]
LOAC events are 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-agonists (SABA) OR >=4 additional puffs of low-dose inhaled Corticosteroid (ICS)/formoterol in a 24-hour period (compared to baseline) on 2 consecutive days
- Increase in ICS >=4 times than the Visit 2 dose
- Severe exacerbation event
13.Time to first LOAC event
[Time Frame baseline:Baseline through Week 48]
LOAC events are 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-agonists (SABA) OR >= 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
Severe exacerbation event
14.Change from baseline in the Asthma Daytime Symptom Diary (ADSD) 7-item daily morning score and in the Asthma Nighttime Symptom Diary (ANSD) 7-item daily evening scores at Weeks 2, 4, 8, 12, 24, 36, 48, and 60
[Time Frame baseline:Baseline to Weeks 2, 4, 8, 12, 24, 36, 48, and 60]
ADSD and ANSD have been designed to measure asthma symptoms. Both have overall score from 0- 10 with higher score indicating worse symptom.
15.Annualized rate of severe asthma exacerbations requiring hospitalization or emergency room or urgent care visit during 48 weeks of treatment
[Time Frame baseline:Baseline through Week 48]
16.Change from baseline in the numbers of inhalations/day of SABA or low-dose ICS/formoterol for symptom relief at Weeks 2, 4, 8, 12, 24, 36, 48, and 60
[Time Frame baseline:Baseline to Weeks 2, 4, 8, 12, 24, 36, 48, and 60]
17.Serum amlitelimab concentrations measured throughout the study
[Time Frame baseline:Baseline thought Week 60]
18.Incidence of anti-amlitelimab antibody positive response
[Time Frame baseline:Baseline through Week 60]
19.Percentage of participants with treatment-emergent adverse events (TEAEs), including local reactions, AEs of special interest (AESIs), serious adverse events (SAEs)
[Time Frame baseline:Baseline through Week 60]
20.Incidence of potentially clinically significant laboratory test, vital signs, and ECG abnormalities in the treatment period
[Time Frame baseline:Baseline through Week 60]
21.Change from baseline in Asthma Quality of Life Questionnaire with Standardized Activities (AQLQ (S)) Self-Administered Score at Weeks 2, 4, 8, 12, 24, 36, and 60
[Time Frame baseline:Baseline to Weeks 2, 4, 8, 12, 24, 36, and 60]
The AQLQ(S) is designed as a self-administered participant reported outcome to measure the functional impairments. The overall score is 1 to 7. Higher AQLQ scores indicate better health-related quality of life.
22.Change from baseline in St. George's Respiratory Questionnaire (SGRQ) at Weeks 2, 4, 8, 12, 24, 36, 48, and 60
[Time Frame baseline:Baseline to Weeks 2, 4, 8, 12, 24, 36, 48, and 60]
The SGRQ is designed to measure and quantify health status in adult patients with chronic airflow limitation. A global score ranges from 0 to 100 where 0 indicates best and 100 indicates worst health.
23.Proportion of participants with a decrease from baseline of at least 4 points in SGRQ total score at Week 48
[Time Frame baseline:Week 48]
The SGRQ is designed to measure and quantify health status in adult patients with chronic airflow limitation. A global score ranges from 0 to 100 where 0 indicates best and 100 indicates worst health.
24.Change from baseline in ACQ-6 score and ACQ-7 at Weeks 2, 4, 8, 12, 24, 36, 48, and 60
[Time Frame baseline:Baseline to Weeks 2, 4, 8, 12, 24, 36, 48, and 60]
The ACQ-6 is a validated asthma assessment tool that consists of 6 self-assessment questions. The overall scale ranges from 0 = 'totally controlled' to 6 = 'severely uncontrolled'. The ACQ-7 is a validated asthma assessment tool that consists of 6 self-assessment questions. The overall scale ranges from 0 = 'totally controlled' to 6 = 'severely uncontrolled'.

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: <= 75age old
• Gender: Both

Include criteria

- The participant must be between the ages of 18 and 75 inclusive at the time of signing the informed consent.
- Moderate to severe asthma diagnosed by a physician for >= 12 months according to stages 4 and 5 of the Global Initiative for Asthma (GINA ).
- Participants on existing therapy with medium to high doses of ICS (>=500 micro g fluticasone propionate daily or comparable ICS dose in combination with at least one additional controller (e.g., long-acting beta agonist [LABA], leukotriene receptor antagonist [LTRA], long-acting muscarinic Antagonist [LAMA], methylxanthines) for at least 3 months.
Note for Japan: participants must be on >=400 micro g of fluticasone propionate daily or equivalent.
- >= 1 severe asthma exacerbation in the past year, with at least one exacerbation during treatment with medium to high doses of ICS (>= 500 micro g fluticasone propionate daily or one dose of ICS comparable).
- Participants with pre-BD forced expiratory volume in 1 second (FEV1) > 40% and < 80% of predicted normal at the screening visit.
- 5-item ACQ-5 score >1.5 at randomization.
- Participants with at least 12% reversibility and 200 mL post-BD FEV after administration of albuterol/salbutamol or levalbuterol/levosalbutamol at screening or documented history of a reversibility test.
- Weight >=40 kg and <=150 kg at the randomization visit.

Exclude criteria

Participants are excluded from the study if any of the following criteria apply:
- Chronic lung disease other than asthma.
- Current or former smoker including active vaping of any products and/or marijuana with cessation within 6 months of screening or history of >10 pack-years.
- Participants who experience a deterioration of asthma that results in emergency treatment or hospitalization, or treatment with systemic steroids at any time from 1 month prior to screening.
- Suspicion of, or confirmed, coronavirus disease 2019 (COVID-19) infection during the screening period including known history of COVID-19 infection within 4 weeks prior to Screening; mechanical ventilation or extracorporeal membrane oxygenation (ECMO) secondary to COVID-19 within 3 months prior to Screening; COVID-19 infection who have not yet sufficiently recovered to participate in the procedures of a clinical trial.
- Active infection or history of clinically significant infection
- Known history of, or suspected, significant current immunosuppression, including history of invasive opportunistic or helminthic infections despite infection resolution or otherwise recurrent infections of abnormal frequency or prolonged duration.
- Active or latent tuberculosis (TB)
- A history of malignancy of any type (excluding basal and squamous cell skin cancer and in situ cervical carcinoma that has been excised and cured >3 years prior to baseline).
- History of solid organ transplant.
- Hepatitis B, C or HIV.
- Pregnant or breastfeeding.
- History (within last 2 years prior to Baseline) of prescription drug or substance abuse, including alcohol, considered significant by the Investigator.
- Any prior use of anti-OX40 or anti-OX40L mAb, including amlitelimab
- Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the Investigator, contraindicates participation in the study

Related Information

• Primary Sponsor: Tanaka Tomoyuki
• Secondary ID(s): NCT05421598,2022-000065-41