Dose Ranging Study of Amlitelimab in Adult Participants With Moderate-to-severe Asthma
- Registration Number
- NCT05421598
- Lead Sponsor
- Sanofi
- Brief Summary
This is a parallel, Phase 2, global, multicenter, randomized, double-blind, placebo-controlled, dose-ranging, four-arms study for treatment.
The purpose of this study is to assess the efficacy, safety, and tolerability of add-on therapy with amlitelimab in adult participants with moderate-to-severe asthma.
Study details include:
* The study duration (per participant) will be up to approximately 76 weeks for participants not going into LTS study and will be up to approximately 64 weeks for participants going into LTS study.
* The randomized treatment duration will be up to approximately 60 weeks.
* The scheduled number of visits will be 13.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 446
- 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 μg 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.
- ≥ 1 severe asthma exacerbation in the past year, with at least one exacerbation during treatment with medium to high doses of ICS (≥ 500 μg 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.
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.
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Initial loading dose of amlitelimab matching placebo on Day 1, followed by one injection of amlitelimab matching placebo Q4W until Week 20 (inclusive) and Q12W starting from Week 24 and thereafter. Amlitelimab dose level 1 Amlitelimab Initial loading dose of amlitelimab on Day 1, followed by one injection of amlitelimab dose level 1 every 4 weeks (Q4W) until Week 20 (inclusive) and every 12 weeks (Q12W) starting from Week 24 and thereafter. Amlitelimab dose level 2 Amlitelimab Initial loading dose of amlitelimab on Day 1, followed by one injection of amlitelimab dose level 2 Q4W until Week 20 (inclusive) and Q12W starting from Week 24 and thereafter. Amlitelimab dose level 3 Amlitelimab Initial loading dose of amlitelimab on Day 1, followed by one injection of amlitelimab dose level 3 Q4W until Week 20 (inclusive) and Q12W starting from Week 24 and thereafter.
- Primary Outcome Measures
Name Time Method Annualized rate of severe exacerbation events over 48 weeks 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 Measures
Name Time Method Change from baseline in Asthma Control Questionnaire 5 (ACQ-5) score at Week 48 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.
Change from baseline in pre-bronchodilator (BD) FEV1 at Week 48 Baseline to Week 48 Change from baseline in pre-bronchodilator (BD) FEV1 at Week 48.
Change from baseline in Asthma Quality of Life Questionnaire with Standardized Activities (AQLQ (S)) Self-Administered Score at Week 48 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.
Change from baseline in ACQ-5 score at Weeks 2, 4, 8, 12, 24, 36, and 60 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.
Change from baseline in pre-BD and post-BD FEV1 Baseline to Weeks 2, 4, 8, 12,16, 24, 36 and 60 Change from baseline in pre-BD and post-BD FEV1.
Change from baseline in forced vital capacity (FVC) Baseline to Weeks 4, 12, 24, 36, 48 and 60 Change from baseline in forced vital capacity (FVC).
Incidence of anti-amlitelimab antibody positive response Baseline through Week 60 Incidence of anti-amlitelimab antibody positive response.
Change from baseline in post-BD FEV1 at Week 48 Baseline to Week 48 Change from baseline in post-BD FEV1 at Week 48.
The absolute change in the percent predicted FEV1 from baseline to Week 48 (pre-BD and post-BD) Baseline to Week 48 The absolute change in the percent predicted FEV1 from baseline to Week 48 (pre-BD and post-BD).
Time to first severe exacerbation event 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.
Change from baseline in peak expiratory flow (PEF) and forced expiratory flow (FEF) 25-75% Baseline to Weeks 4, 12, 24, 36, 48 and 60 Change from baseline in peak expiratory flow (PEF) and forced expiratory flow (FEF) 25-75%.
Time to first LOAC event 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 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 eventIncidence of potentially clinically significant laboratory test, vital signs, and ECG abnormalities in the treatment period Baseline through Week 60 Incidence of potentially clinically significant laboratory test, vital signs, and ECG abnormalities in the treatment period.
Change from baseline in FeNO at Weeks 2, 4, 8, 12, 16, 24, 36, 48 and 60 Baseline to Weeks 2, 4, 8, 12, 16, 24, 36, 48 and 60 Change from baseline in FeNO at Weeks 2, 4, 8, 12, 16, 24, 36, 48 and 60.
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 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.
Change from baseline in St. George's Respiratory Questionnaire (SGRQ) at Weeks 2, 4, 8, 12, 24, 36, 48, and 60 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.
Annualized rate of loss of asthma control (LOAC) events during 48 weeks of treatment 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 eventAnnualized rate of severe asthma exacerbations requiring hospitalization or emergency room or urgent care visit during 48 weeks of treatment Baseline through Week 48 Annualized rate of severe asthma exacerbations requiring hospitalization or emergency room or urgent care visit during 48 weeks of treatment.
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 Baseline to Weeks 2, 4, 8, 12, 24, 36, 48, and 60 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.
Serum amlitelimab concentrations measured throughout the study Baseline thought Week 60 Serum amlitelimab concentrations measured throughout the study.
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 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.
Proportion of participants with a decrease from baseline of at least 4 points in SGRQ total score at Week 48 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.
Change from baseline in ACQ-6 score and ACQ-7 at Weeks 2, 4, 8, 12, 24, 36, 48, and 60 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 unc7ntrolled. 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.
Percentage of participants with treatment-emergent adverse events (TEAEs), including local reactions, AEs of special interest (AESIs), serious adverse events (SAEs) Baseline through Week 60 Percentage of participants with treatment-emergent adverse events (TEAEs), including local reactions, AEs of special interest (AESIs), serious adverse events (SAEs).
Trial Locations
- Locations (113)
Investigational Site Number : 1240003
🇨🇦Quebec, Canada
Investigational Site Number : 1240007
🇨🇦Trois-Rivieres, Quebec, Canada
Treasure Valley Medical Research Site Number : 8400031
🇺🇸Boise, Idaho, United States
University of Kansas Medical Center Site Number : 8400016
🇺🇸Kansas City, Kansas, United States
Johns Hopkins University School of Medicine Site Number : 8400012
🇺🇸Baltimore, Maryland, United States
The South Bend Clinic, LLC Site Number : 8400033
🇺🇸South Bend, Indiana, United States
University of California San Diego Health Site Number : 8400026
🇺🇸La Jolla, California, United States
California Allergy and Asthma Medical Group, Inc. Site Number : 8400002
🇺🇸Los Angeles, California, United States
Allergy Asthma Associates of Santa Clara Valley Site Number : 8400019
🇺🇸San Jose, California, United States
Bensch Clinical Research LLC Site Number : 8400004
🇺🇸Stockton, California, United States
Allianz Research Institute Site Number : 8400023
🇺🇸Westminster, California, United States
Helix Biomedics, LLC Site Number : 8400029
🇺🇸Boynton Beach, Florida, United States
Renaissance Research and Medical Group, Inc Site Number : 8400030
🇺🇸Cape Coral, Florida, United States
Beautiful Minds Clinical Research Center Site Number : 8400027
🇺🇸Cutler Bay, Florida, United States
Reliable Clinical Research, LLC Site Number : 8400020
🇺🇸Hialeah, Florida, United States
Savin Medical Group, LLC Site Number : 8400015
🇺🇸Miami, Florida, United States
Pines Care Research Center LLC Site Number : 8400028
🇺🇸Pembroke Pines, Florida, United States
Headlands Research Detroit Site Number : 8400032
🇺🇸Southfield, Michigan, United States
Henderson Clinical Trials Site Number : 8400037
🇺🇸Henderson, Nevada, United States
Asthma and Allergy Center Site Number : 8400005
🇺🇸Toledo, Ohio, United States
OK Clinical Research, LLC Site Number : 8400001
🇺🇸Edmond, Oklahoma, United States
Allergy, Asthma and Clinical Research Center Site Number : 8400035
🇺🇸Oklahoma City, Oklahoma, United States
TTS Research Site Number : 8400011
🇺🇸Boerne, Texas, United States
Investigational Site Number : 0320001
🇦🇷Caba, Buenos Aires, Argentina
Investigational Site Number : 0320002
🇦🇷Caba, Buenos Aires, Argentina
Investigational Site Number : 0320008
🇦🇷La Plata, Buenos Aires, Argentina
Investigational Site Number : 0320009
🇦🇷Buenos Aires, Ciudad De Buenos Aires, Argentina
Investigational Site Number : 0320006
🇦🇷Rosario, Santa Fe, Argentina
Investigational Site Number : 0320007
🇦🇷Rosario, Santa Fe, Argentina
Investigational Site Number : 0320005
🇦🇷Rosario, Santa Fe, Argentina
Investigational Site Number : 0320004
🇦🇷Buenos Aires, Argentina
Investigational Site Number : 0320003
🇦🇷Ciudad Autonoma Buenos Aires, Argentina
Proar Site Number : 0760004
🇧🇷Salvador, Bahia, Brazil
CEDOES - Centro de Diagnostico e Pesquisa de Osteoporose do ES Site Number : 0760002
🇧🇷Vitoria, Espírito Santo, Brazil
Centro Avancado de Oncologia CECAN - Liga Contra o Cancer Site Number : 0760010
🇧🇷Natal, Rio Grande Do Norte, Brazil
Instituto Mederi de Pesquisa e Saude Site Number : 0760001
🇧🇷Passo Fundo, Rio Grande Do Sul, Brazil
Irmandade da Santa Casa de Misericordia de Porto Alegre Site Number : 0760007
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Hospital Sao Lucas da PUCRS Site Number : 0760006
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Hospital das Clinicas de Sao Paulo Site Number : 0760008
🇧🇷Sao Paulo, São Paulo, Brazil
Clinica de Alergia Martti Antila Site Number : 0760003
🇧🇷Sorocaba, São Paulo, Brazil
Investigational Site Number : 1240006
🇨🇦Brampton, Ontario, Canada
Investigational Site Number : 1240008
🇨🇦Ottawa, Ontario, Canada
Investigational Site Number : 1240005
🇨🇦Toronto, Ontario, Canada
Investigational Site Number : 1520006
🇨🇱Talca, Maule, Chile
Investigational Site Number : 1520007
🇨🇱Santiago, Reg Metropolitana De Santiago, Chile
Investigational Site Number : 1520001
🇨🇱Santiago, Reg Metropolitana De Santiago, Chile
Investigational Site Number : 1520002
🇨🇱Santiago, Reg Metropolitana De Santiago, Chile
Investigational Site Number : 1520009
🇨🇱Santiago, Reg Metropolitana De Santiago, Chile
Investigational Site Number : 1520008
🇨🇱Santiago, Reg Metropolitana De Santiago, Chile
Investigational Site Number : 1520003
🇨🇱Santiago, Reg Metropolitana De Santiago, Chile
Investigational Site Number : 1520005
🇨🇱Quillota, Valparaíso, Chile
Investigational Site Number : 3480007
🇭🇺Budapest, Hungary
Investigational Site Number : 3480009
🇭🇺Edelény, Hungary
Investigational Site Number : 3480011
🇭🇺Gödöllö, Hungary
Investigational Site Number : 3480002
🇭🇺Hajdunánás, Hungary
Investigational Site Number : 3480004
🇭🇺Mosonmagyaróvár, Hungary
Investigational Site Number : 3480006
🇭🇺Puspokladany, Hungary
Investigational Site Number : 3480012
🇭🇺Szazhalombatta, Hungary
Investigational Site Number : 3480003
🇭🇺Szombathely, Hungary
Investigational Site Number : 3800002
🇮🇹Cona (FE), Emilia-Romagna, Italy
Investigational Site Number : 3800003
🇮🇹Roma, Lazio, Italy
Investigational Site Number : 3800004
🇮🇹Napoli, Italy
Investigational Site Number : 3800001
🇮🇹Verona, Italy
Investigational Site Number : 3920014
🇯🇵Narita-shi, Chiba, Japan
Investigational Site Number : 3920002
🇯🇵Kamakura-shi, Kanagawa, Japan
Investigational Site Number : 3920016
🇯🇵Yokohama-shi, Kanagawa, Japan
Investigational Site Number : 3920006
🇯🇵Yokohama-shi, Kanagawa, Japan
Investigational Site Number : 3920013
🇯🇵Nankoku-shi, Kochi, Japan
Investigational Site Number : 3920015
🇯🇵Kumamoto-shi, Kumamoto, Japan
Investigational Site Number : 3920010
🇯🇵Sakai-shi, Osaka, Japan
Investigational Site Number : 3920017
🇯🇵Chuo-ku, Tokyo, Japan
Investigational Site Number : 3920005
🇯🇵Chuo-ku, Tokyo, Japan
Investigational Site Number : 3920004
🇯🇵Chuo-ku, Tokyo, Japan
Investigational Site Number : 3920020
🇯🇵Kiyose-shi, Tokyo, Japan
Investigational Site Number : 3920001
🇯🇵Shinagawa-ku, Tokyo, Japan
Investigational Site Number : 3920011
🇯🇵Shinjuku-ku, Tokyo, Japan
Investigational Site Number : 3920009
🇯🇵Tachikawa-shi, Tokyo, Japan
Investigational Site Number : 3920018
🇯🇵Toshima-ku, Tokyo, Japan
Investigational Site Number : 3920008
🇯🇵Fukuoka-shi, Japan
Investigational Site Number : 3920019
🇯🇵Hiroshima-shi, Japan
Investigational Site Number : 4100004
🇰🇷Daegu, Daegu-gwangyeoksi, Korea, Republic of
Investigational Site Number : 4100003
🇰🇷Seoul, Seoul-teukbyeolsi, Korea, Republic of
Investigational Site Number : 4100001
🇰🇷Seoul, Seoul-teukbyeolsi, Korea, Republic of
Investigational Site Number : 4100005
🇰🇷Seoul, Seoul-teukbyeolsi, Korea, Republic of
Investigational Site Number : 4100002
🇰🇷Seoul, Seoul-teukbyeolsi, Korea, Republic of
Investigational Site Number : 4100006
🇰🇷Seoul, Seoul-teukbyeolsi, Korea, Republic of
Investigational Site Number : 4100007
🇰🇷Seongnam-si, Gyeonggi-do, Korea, Republic of
Investigational Site Number : 4840001
🇲🇽Guadalajara, Jalisco, Mexico
Investigational Site Number : 4840005
🇲🇽Guadalajara, Jalisco, Mexico
Investigational Site Number : 4840002
🇲🇽Chihuahua, Mexico
Investigational Site Number : 4840004
🇲🇽Durango, Durango, Mexico
Investigational Site Number : 4840006
🇲🇽Tlalnepantla, Mexico
Investigational Site Number : 4840008
🇲🇽Yucatan, Mexico
Investigational Site Number : 6160006
🇵🇱Krakow, Malopolskie, Poland
Investigational Site Number : 6160004
🇵🇱Bialystok, Podlaskie, Poland
Investigational Site Number : 6160001
🇵🇱Poznan, Wielkopolskie, Poland
Investigational Site Number : 6160003
🇵🇱Elblag, Poland
Investigational Site Number : 6160002
🇵🇱Gdansk, Poland
Investigational Site Number : 6160007
🇵🇱Tarnow, Poland
Investigational Site Number : 7100007
🇿🇦Benoni, South Africa
Investigational Site Number : 7100002
🇿🇦Cape Town, South Africa
Investigational Site Number : 7100005
🇿🇦Cape Town, South Africa
Investigational Site Number : 7100001
🇿🇦Cape Town, South Africa
Investigational Site Number : 7100003
🇿🇦Durban, South Africa
Investigational Site Number : 7100006
🇿🇦George, South Africa
Investigational Site Number : 7100008
🇿🇦Johannesburg, South Africa
Investigational Site Number : 7100004
🇿🇦Middelburg, South Africa
Investigational Site Number : 7920001
🇹🇷Istanbul, Turkey
Investigational Site Number : 7920003
🇹🇷Izmir, Turkey
Investigational Site Number : 7920008
🇹🇷Kayseri, Turkey
Investigational Site Number : 7920005
🇹🇷Kocaeli, Turkey
Investigational Site Number : 7920002
🇹🇷Mersin, Turkey
Investigational Site Number : 8260001
🇬🇧Bradford, United Kingdom