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

Asthma Clinical Trial

— TIDE-asthma  

Official title:

A Randomized, Double-blind, Placebo-controlled, Parallel-group, Dose Ranging Study to Assess the Efficacy, Safety, and Tolerability of Subcutaneous Amlitelimab in Adult Participants With Moderate-to-severe Asthma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05421598
• Other study ID #: DRI17509
• Secondary ID: U1111-1272-26122
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: June 30, 2022
• Est. completion date: March 21, 2025

Study information

• Verified date: November 2023
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 446
• Est. completion date: March 21, 2025
• Est. primary completion date: October 4, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion 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 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.

Exclusion 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.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Related Conditions & MeSH terms

• Asthma

Intervention

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

Locations

Country	Name	City	State
Argentina	Investigational Site Number : 0320004	Buenos Aires
Argentina	Investigational Site Number : 0320009	Buenos Aires	Ciudad De Buenos Aires
Argentina	Investigational Site Number : 0320001	Caba	Buenos Aires
Argentina	Investigational Site Number : 0320002	Caba	Buenos Aires
Argentina	Investigational Site Number : 0320003	Ciudad Autonoma Buenos Aires
Argentina	Investigational Site Number : 0320008	La Plata	Buenos Aires
Argentina	Investigational Site Number : 0320005	Rosario	Santa Fe
Argentina	Investigational Site Number : 0320006	Rosario	Santa Fe
Argentina	Investigational Site Number : 0320007	Rosario	Santa Fe
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	Hospital Sao Lucas da PUCRS Site Number : 0760006	Porto Alegre	Rio Grande Do Sul
Brazil	Irmandade da Santa Casa de Misericordia de Porto Alegre Site Number : 0760007	Porto Alegre	Rio Grande Do Sul
Brazil	Proar Site Number : 0760004	Salvador	Bahia
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	CEDOES - Centro de Diagnostico e Pesquisa de Osteoporose do ES Site Number : 0760002	Vitoria	Espírito Santo
Canada	Investigational Site Number : 1240006	Brampton	Ontario
Canada	Investigational Site Number : 1240008	Ottawa	Ontario
Canada	Investigational Site Number : 1240003	Quebec
Canada	Investigational Site Number : 1240005	Toronto	Ontario
Canada	Investigational Site Number : 1240007	Trois-Rivieres	Quebec
Canada	Investigational Site Number : 1240009	Vancouver	British Columbia
Chile	Investigational Site Number : 1520005	Quillota	Valparaíso
Chile	Investigational Site Number : 1520001	Santiago	Reg Metropolitana De Santiago
Chile	Investigational Site Number : 1520002	Santiago	Reg Metropolitana De Santiago
Chile	Investigational Site Number : 1520003	Santiago	Reg Metropolitana De Santiago
Chile	Investigational Site Number : 1520007	Santiago	Reg Metropolitana De Santiago
Chile	Investigational Site Number : 1520008	Santiago	Reg Metropolitana De Santiago
Chile	Investigational Site Number : 1520009	Santiago	Reg Metropolitana De Santiago
Chile	Investigational Site Number : 1520006	Talca	Maule
Hungary	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
Italy	Investigational Site Number : 3800002	Cona (FE)	Emilia-Romagna
Italy	Investigational Site Number : 3800004	Napoli
Italy	Investigational Site Number : 3800003	Roma	Lazio
Italy	Investigational Site Number : 3800001	Verona
Japan	Investigational Site Number : 3920004	Chuo-ku	Tokyo
Japan	Investigational Site Number : 3920005	Chuo-ku	Tokyo
Japan	Investigational Site Number : 3920017	Chuo-ku	Tokyo
Japan	Investigational Site Number : 3920008	Fukuoka-shi
Japan	Investigational Site Number : 3920019	Hiroshima-shi
Japan	Investigational Site Number : 3920003	Itabashi-ku	Tokyo
Japan	Investigational Site Number : 3920002	Kamakura-shi	Kanagawa
Japan	Investigational Site Number : 3920012	Kanazawa-shi	Ishikawa
Japan	Investigational Site Number : 3920020	Kiyose-shi	Tokyo
Japan	Investigational Site Number : 3920015	Kumamoto-shi	Kumamoto
Japan	Investigational Site Number : 3920007	Nagoya-shi	Aichi
Japan	Investigational Site Number : 3920013	Nankoku-shi	Kochi
Japan	Investigational Site Number : 3920014	Narita-shi	Chiba
Japan	Investigational Site Number : 3920010	Sakai-shi	Osaka
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 : 3920006	Yokohama-shi	Kanagawa
Japan	Investigational Site Number : 3920016	Yokohama-shi	Kanagawa
Korea, Republic of	Investigational Site Number : 4100004	Daegu	Daegu-gwangyeoksi
Korea, Republic of	Investigational Site Number : 4100007	Seongnam-si, Gyeonggi-do
Korea, Republic of	Investigational Site Number : 4100001	Seoul	Seoul-teukbyeolsi
Korea, Republic of	Investigational Site Number : 4100002	Seoul	Seoul-teukbyeolsi
Korea, Republic of	Investigational Site Number : 4100003	Seoul	Seoul-teukbyeolsi
Korea, Republic of	Investigational Site Number : 4100005	Seoul	Seoul-teukbyeolsi
Korea, Republic of	Investigational Site Number : 4100006	Seoul	Seoul-teukbyeolsi
Mexico	Investigational Site Number : 4840002	Chihuahua
Mexico	Investigational Site Number : 4840004	Durango, Durango
Mexico	Investigational Site Number : 4840001	Guadalajara	Jalisco
Mexico	Investigational Site Number : 4840005	Guadalajara	Jalisco
Mexico	Investigational Site Number : 4840006	Tlalnepantla
Mexico	Investigational Site Number : 4840008	Yucatan
Poland	Investigational Site Number : 6160004	Bialystok	Podlaskie
Poland	Investigational Site Number : 6160003	Elblag
Poland	Investigational Site Number : 6160002	Gdansk
Poland	Investigational Site Number : 6160006	Krakow	Malopolskie
Poland	Investigational Site Number : 6160001	Poznan	Wielkopolskie
Poland	Investigational Site Number : 6160007	Tarnow
South Africa	Investigational Site Number : 7100007	Benoni
South Africa	Investigational Site Number : 7100001	Cape Town
South Africa	Investigational Site Number : 7100002	Cape Town
South Africa	Investigational Site Number : 7100005	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
Turkey	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
United Kingdom	Investigational Site Number : 8260001	Bradford
United Kingdom	Investigational Site Number : 8260002	Liverpool
United Kingdom	Investigational Site Number : 8260003	London	London, City Of
United States	Michigan Medicine (University of Michigan) Site Number : 8400006	Ann Arbor	Michigan
United States	Johns Hopkins University School of Medicine Site Number : 8400012	Baltimore	Maryland
United States	TTS Research Site Number : 8400011	Boerne	Texas
United States	Treasure Valley Medical Research Site Number : 8400031	Boise	Idaho
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	OK Clinical Research, LLC Site Number : 8400001	Edmond	Oklahoma
United States	Henderson Clinical Trials Site Number : 8400037	Henderson	Nevada
United States	Reliable Clinical Research, LLC Site Number : 8400020	Hialeah	Florida
United States	University of Kansas Medical Center Site Number : 8400016	Kansas City	Kansas
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	PRX Research Site Number : 8400036	Mesquite	Texas
United States	Savin Medical Group, LLC Site Number : 8400015	Miami	Florida
United States	Montana Medical Research Site Number : 8400034	Missoula	Montana
United States	Allergy Associates of Utah Site Number : 8400003	Murray	Utah
United States	Allergy, Asthma and Clinical Research Center Site Number : 8400035	Oklahoma City	Oklahoma
United States	Pines Care Research Center LLC Site Number : 8400028	Pembroke Pines	Florida
United States	Allergy Asthma Associates of Santa Clara Valley Site Number : 8400019	San Jose	California
United States	South Bend Clinic Site Number : 8400033	South Bend	Indiana
United States	Headlands Research Detroit Site Number : 8400032	Southfield	Michigan
United States	Bensch Clinical Research LLC Site Number : 8400004	Stockton	California
United States	Asthma and Allergy Center Site Number : 8400005	Toledo	Ohio
United States	Allianz Research Institute Site Number : 8400023	Westminster	California

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Canada,  Chile,  Hungary,  Italy,  Japan,  Korea, Republic of,  Mexico,  Poland,  South Africa,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Annualized rate of severe exacerbation events over 48 weeks	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.	Baseline through Week 48
Secondary	Change from baseline in pre-bronchodilator (BD) FEV1 at Week 48	Change from baseline in pre-bronchodilator (BD) FEV1 at Week 48.	Baseline to Week 48
Secondary	Change from baseline in Asthma Control Questionnaire 5 (ACQ-5) score at 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.	Baseline to Week 48
Secondary	Change from baseline in Asthma Quality of Life Questionnaire with Standardized Activities (AQLQ (S)) Self-Administered Score at 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.	Baseline to Week 48
Secondary	Change from baseline in post-BD FEV1 at Week 48	Change from baseline in post-BD FEV1 at Week 48.	Baseline to Week 48
Secondary	The absolute change in the percent predicted FEV1 from baseline to Week 48 (pre-BD and post-BD)	The absolute change in the percent predicted FEV1 from baseline to Week 48 (pre-BD and post-BD).	Baseline to Week 48
Secondary	Change from baseline in ACQ-5 score at 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.	Baseline to Weeks 2, 4, 8, 12, 24, 36, and 60
Secondary	Time to first severe exacerbation event	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.	Baseline through Week 48
Secondary	Change from baseline in pre-BD and post-BD FEV1	Change from baseline in pre-BD and post-BD FEV1.	Baseline to Weeks 2, 4, 8, 12,16, 24, 36 and 60
Secondary	Change from baseline in peak expiratory flow (PEF) and forced expiratory flow (FEF) 25-75%	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
Secondary	Change from baseline in forced vital capacity (FVC)	Change from baseline in forced vital capacity (FVC).	Baseline to Weeks 4, 12, 24, 36, 48 and 60
Secondary	Change from baseline in FeNO at 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.	Baseline to Weeks 2, 4, 8, 12, 16, 24, 36, 48 and 60
Secondary	Annualized rate of loss of asthma control (LOAC) events during 48 weeks of treatment	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	Baseline through Week 48
Secondary	Time to first LOAC event	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 event	Baseline through Week 48
Secondary	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	ADSD and ANSD have been designed to measure asthma symptoms. Both have overall score from 0- 10 with higher score indicating worse symptom.	Baseline to Weeks 2, 4, 8, 12, 24, 36, 48, and 60
Secondary	Annualized rate of severe asthma exacerbations requiring hospitalization or emergency room or urgent care visit during 48 weeks of treatment	Annualized rate of severe asthma exacerbations requiring hospitalization or emergency room or urgent care visit during 48 weeks of treatment.	Baseline through Week 48
Secondary	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	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
Secondary	Serum amlitelimab concentrations measured throughout the study	Serum amlitelimab concentrations measured throughout the study.	Baseline thought Week 60
Secondary	Incidence of anti-amlitelimab antibody positive response	Incidence of anti-amlitelimab antibody positive response.	Baseline through Week 60
Secondary	Percentage of participants with treatment-emergent adverse events (TEAEs), including local reactions, AEs of special interest (AESIs), serious adverse events (SAEs)	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
Secondary	Incidence of potentially clinically significant laboratory test, vital signs, and ECG abnormalities in the treatment period	Incidence of potentially clinically significant laboratory test, vital signs, and ECG abnormalities in the treatment period.	Baseline through Week 60
Secondary	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	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.	Baseline to Weeks 2, 4, 8, 12, 24, 36, and 60
Secondary	Change from baseline in St. George's Respiratory Questionnaire (SGRQ) at 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.	Baseline to Weeks 2, 4, 8, 12, 24, 36, 48, and 60
Secondary	Proportion of participants with a decrease from baseline of at least 4 points in SGRQ total score at 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.	Week 48
Secondary	Change from baseline in ACQ-6 score and ACQ-7 at 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.	Baseline to Weeks 2, 4, 8, 12, 24, 36, 48, and 60