Clinical trial NCT05421598: Dose Ranging Study of Amlitelimab in Adult Participants With Moderate-to-severe 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Asthma
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2022-06-16
Enrollment: 446
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Annualized rate of severe exacerbation events over 48 weeks
timeFrame: Baseline through Week 48
Secondary outcomes:
measure: Change from baseline in pre-bronchodilator (BD) FEV1 at Week 48
timeFrame: Baseline to Week 48
measure: Change from baseline in Asthma Control Questionnaire 5 (ACQ-5) score at Week 48
timeFrame: Baseline to Week 48
measure: Change from baseline in Asthma Quality of Life Questionnaire with Standardized Activities (AQLQ (S)) Self-Administered Score at Week 48
timeFrame: Baseline to Week 48
measure: Change from baseline in post-BD FEV1 at Week 48
timeFrame: Baseline to Week 48
measure: The absolute change in the percent predicted FEV1 from baseline to Week 48 (pre-BD and post-BD)
timeFrame: Baseline to Week 48
measure: Change from baseline in ACQ-5 score at Weeks 2, 4, 8, 12, 24, 36, and 60
timeFrame: Baseline to Weeks 2, 4, 8, 12, 24, 36, and 60
measure: Time to first severe exacerbation event
timeFrame: Baseline through Week 48
measure: Change from baseline in pre-BD and post-BD FEV1
timeFrame: Baseline to Weeks 2, 4, 8, 12,16, 24, 36 and 60
measure: Change from baseline in peak expiratory flow (PEF) and forced expiratory flow (FEF) 25-75%
timeFrame: Baseline to Weeks 4, 12, 24, 36, 48 and 60
measure: Change from baseline in forced vital capacity (FVC)
timeFrame: Baseline to Weeks 4, 12, 24, 36, 48 and 60
measure: Change from baseline in FeNO at Weeks 2, 4, 8, 12, 16, 24, 36, 48 and 60
timeFrame: Baseline to Weeks 2, 4, 8, 12, 16, 24, 36, 48 and 60
measure: Annualized rate of loss of asthma control (LOAC) events during 48 weeks of treatment
timeFrame: Baseline through Week 48
measure: Time to first LOAC event
timeFrame: Baseline through Week 48
measure: 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
timeFrame: Baseline to Weeks 2, 4, 8, 12, 24, 36, 48, and 60
measure: Annualized rate of severe asthma exacerbations requiring hospitalization or emergency room or urgent care visit during 48 weeks of treatment
timeFrame: Baseline through Week 48
measure: 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
timeFrame: Baseline to Weeks 2, 4, 8, 12, 24, 36, 48, and 60
measure: Serum amlitelimab concentrations measured throughout the study
timeFrame: Baseline thought Week 60
measure: Incidence of anti-amlitelimab antibody positive response
timeFrame: Baseline through Week 60
measure: Percentage of participants with treatment-emergent adverse events (TEAEs), including local reactions, AEs of special interest (AESIs), serious adverse events (SAEs)
timeFrame: Baseline through Week 60
measure: Incidence of potentially clinically significant laboratory test, vital signs, and ECG abnormalities in the treatment period
timeFrame: Baseline through Week 60
measure: 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
timeFrame: Baseline to Weeks 2, 4, 8, 12, 24, 36, and 60
measure: Change from baseline in St. George's Respiratory Questionnaire (SGRQ) at Weeks 2, 4, 8, 12, 24, 36, 48, and 60
timeFrame: Baseline to Weeks 2, 4, 8, 12, 24, 36, 48, and 60
measure: Proportion of participants with a decrease from baseline of at least 4 points in SGRQ total score at Week 48
timeFrame: Week 48
measure: Change from baseline in ACQ-6 score and ACQ-7 at Weeks 2, 4, 8, 12, 24, 36, 48, and 60
timeFrame: Baseline to Weeks 2, 4, 8, 12, 24, 36, 48, and 60
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: University of California San Diego Health Site Number : 8400026
state: California
city: Los Angeles
country: United States
facility: California Allergy and Asthma Medical Group, Inc. Site Number : 8400002
state: California
city: San Jose
country: United States
facility: Allergy Asthma Associates of Santa Clara Valley Site Number : 8400019
state: California
city: Stockton
country: United States
facility: Bensch Clinical Research LLC Site Number : 8400004
state: California
city: Westminster
country: United States
facility: Allianz Research Institute Site Number : 8400023
state: California
city: Boynton Beach
country: United States
facility: Helix Biomedics, LLC Site Number : 8400029
state: Florida
city: Cape Coral
country: United States
facility: Renaissance Research and Medical Group, Inc Site Number : 8400030
state: Florida
city: Cutler Bay
country: United States
facility: Beautiful Minds Clinical Research Center Site Number : 8400027
state: Florida
city: Hialeah
country: United States
facility: Reliable Clinical Research, LLC Site Number : 8400020
state: Florida
city: Miami
country: United States
facility: Savin Medical Group, LLC Site Number : 8400015
state: Florida
city: Pembroke Pines
country: United States
facility: Pines Care Research Center LLC Site Number : 8400028
state: Florida
city: Boise
country: United States
facility: Treasure Valley Medical Research Site Number : 8400031
state: Idaho
city: South Bend
country: United States
facility: The South Bend Clinic, LLC Site Number : 8400033
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Medical Center Site Number : 8400016
state: Kansas
city: Baltimore
country: United States
facility: Johns Hopkins University School of Medicine Site Number : 8400012
state: Maryland
city: Southfield
country: United States
facility: Headlands Research Detroit Site Number : 8400032
state: Michigan
city: Henderson
country: United States
facility: Henderson Clinical Trials Site Number : 8400037
state: Nevada
city: Toledo
country: United States
facility: Asthma and Allergy Center Site Number : 8400005
state: Ohio
city: Edmond
country: United States
facility: OK Clinical Research, LLC Site Number : 8400001
state: Oklahoma
city: Oklahoma City
country: United States
facility: Allergy, Asthma and Clinical Research Center Site Number : 8400035
state: Oklahoma
city: Boerne
country: United States
facility: TTS Research Site Number : 8400011
state: Texas
city: Caba
country: Argentina
facility: Investigational Site Number : 0320001
state: Buenos Aires
city: Caba
country: Argentina
facility: Investigational Site Number : 0320002
state: Buenos Aires
city: La Plata
country: Argentina
facility: Investigational Site Number : 0320008
state: Buenos Aires
city: Buenos Aires
country: Argentina
facility: Investigational Site Number : 0320009
state: Ciudad De Buenos Aires
city: Rosario
country: Argentina
facility: Investigational Site Number : 0320006
state: Santa Fe
city: Rosario
country: Argentina
facility: Investigational Site Number : 0320007
state: Santa Fe
city: Rosario
country: Argentina
facility: Investigational Site Number : 0320005
state: Santa Fe
city: Buenos Aires
country: Argentina
facility: Investigational Site Number : 0320004
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Investigational Site Number : 0320003
city: Salvador
country: Brazil
facility: Proar Site Number : 0760004
state: Bahia
city: Vitoria
country: Brazil
facility: CEDOES - Centro de Diagnostico e Pesquisa de Osteoporose do ES Site Number : 0760002
state: Espírito Santo
city: Natal
country: Brazil
facility: Centro Avancado de Oncologia CECAN - Liga Contra o Cancer Site Number : 0760010
state: Rio Grande Do Norte
city: Passo Fundo
country: Brazil
facility: Instituto Mederi de Pesquisa e Saude Site Number : 0760001
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Irmandade da Santa Casa de Misericordia de Porto Alegre Site Number : 0760007
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Hospital Sao Lucas da PUCRS Site Number : 0760006
state: Rio Grande Do Sul
city: Sao Paulo
country: Brazil
facility: Hospital das Clinicas de Sao Paulo Site Number : 0760008
state: São Paulo
city: Sorocaba
country: Brazil
facility: Clinica de Alergia Martti Antila Site Number : 0760003
state: São Paulo
city: Brampton
country: Canada
facility: Investigational Site Number : 1240006
state: Ontario
city: Ottawa
country: Canada
facility: Investigational Site Number : 1240008
state: Ontario
city: Toronto
country: Canada
facility: Investigational Site Number : 1240005
state: Ontario
city: Trois-Rivieres
country: Canada
facility: Investigational Site Number : 1240007
state: Quebec
city: Quebec
country: Canada
facility: Investigational Site Number : 1240003
city: Talca
country: Chile
facility: Investigational Site Number : 1520006
state: Maule
city: Santiago
country: Chile
facility: Investigational Site Number : 1520007
state: Reg Metropolitana De Santiago
city: Santiago
country: Chile
facility: Investigational Site Number : 1520001
state: Reg Metropolitana De Santiago
city: Santiago
country: Chile
facility: Investigational Site Number : 1520002
state: Reg Metropolitana De Santiago
city: Santiago
country: Chile
facility: Investigational Site Number : 1520009
state: Reg Metropolitana De Santiago
city: Santiago
country: Chile
facility: Investigational Site Number : 1520008
state: Reg Metropolitana De Santiago
city: Santiago
country: Chile
facility: Investigational Site Number : 1520003
state: Reg Metropolitana De Santiago
city: Quillota
country: Chile
facility: Investigational Site Number : 1520005
state: Valparaíso
city: Budapest
country: Hungary
facility: Investigational Site Number : 3480007
city: Edelény
country: Hungary
facility: Investigational Site Number : 3480009
city: Gödöllö
country: Hungary
facility: Investigational Site Number : 3480011
city: Hajdunánás
country: Hungary
facility: Investigational Site Number : 3480002
city: Mosonmagyaróvár
country: Hungary
facility: Investigational Site Number : 3480004
city: Puspokladany
country: Hungary
facility: Investigational Site Number : 3480006
city: Szazhalombatta
country: Hungary
facility: Investigational Site Number : 3480012
city: Szombathely
country: Hungary
facility: Investigational Site Number : 3480003
city: Cona (FE)
country: Italy
facility: Investigational Site Number : 3800002
state: Emilia-Romagna
city: Roma
country: Italy
facility: Investigational Site Number : 3800003
state: Lazio
city: Napoli
country: Italy
facility: Investigational Site Number : 3800004
city: Verona
country: Italy
facility: Investigational Site Number : 3800001
city: Narita-shi
country: Japan
facility: Investigational Site Number : 3920014
state: Chiba
city: Kamakura-shi
country: Japan
facility: Investigational Site Number : 3920002
state: Kanagawa
city: Yokohama-shi
country: Japan
facility: Investigational Site Number : 3920016
state: Kanagawa
city: Yokohama-shi
country: Japan
facility: Investigational Site Number : 3920006
state: Kanagawa
city: Nankoku-shi
country: Japan
facility: Investigational Site Number : 3920013
state: Kochi
city: Kumamoto-shi
country: Japan
facility: Investigational Site Number : 3920015
state: Kumamoto
city: Sakai-shi
country: Japan
facility: Investigational Site Number : 3920010
state: Osaka
city: Chuo-ku
country: Japan
facility: Investigational Site Number : 3920017
state: Tokyo
city: Chuo-ku
country: Japan
facility: Investigational Site Number : 3920005
state: Tokyo
city: Chuo-ku
country: Japan
facility: Investigational Site Number : 3920004
state: Tokyo
city: Kiyose-shi
country: Japan
facility: Investigational Site Number : 3920020
state: Tokyo
city: Shinagawa-ku
country: Japan
facility: Investigational Site Number : 3920001
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Investigational Site Number : 3920011
state: Tokyo
city: Tachikawa-shi
country: Japan
facility: Investigational Site Number : 3920009
state: Tokyo
city: Toshima-ku
country: Japan
facility: Investigational Site Number : 3920018
state: Tokyo
city: Fukuoka-shi
country: Japan
facility: Investigational Site Number : 3920008
city: Hiroshima-shi
country: Japan
facility: Investigational Site Number : 3920019
city: Daegu
country: Korea, Republic of
facility: Investigational Site Number : 4100004
state: Daegu-gwangyeoksi
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number : 4100003
state: Seoul-teukbyeolsi
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number : 4100001
state: Seoul-teukbyeolsi
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number : 4100005
state: Seoul-teukbyeolsi
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number : 4100002
state: Seoul-teukbyeolsi
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number : 4100006
state: Seoul-teukbyeolsi
city: Seongnam-si, Gyeonggi-do
country: Korea, Republic of
facility: Investigational Site Number : 4100007
city: Guadalajara
country: Mexico
facility: Investigational Site Number : 4840001
state: Jalisco
city: Guadalajara
country: Mexico
facility: Investigational Site Number : 4840005
state: Jalisco
city: Chihuahua
country: Mexico
facility: Investigational Site Number : 4840002
city: Durango, Durango
country: Mexico
facility: Investigational Site Number : 4840004
city: Tlalnepantla
country: Mexico
facility: Investigational Site Number : 4840006
city: Yucatan
country: Mexico
facility: Investigational Site Number : 4840008
city: Krakow
country: Poland
facility: Investigational Site Number : 6160006
state: Malopolskie
city: Bialystok
country: Poland
facility: Investigational Site Number : 6160004
state: Podlaskie
city: Poznan
country: Poland
facility: Investigational Site Number : 6160001
state: Wielkopolskie
city: Elblag
country: Poland
facility: Investigational Site Number : 6160003
city: Gdansk
country: Poland
facility: Investigational Site Number : 6160002
city: Tarnow
country: Poland
facility: Investigational Site Number : 6160007
city: Benoni
country: South Africa
facility: Investigational Site Number : 7100007
city: Cape Town
country: South Africa
facility: Investigational Site Number : 7100002
city: Cape Town
country: South Africa
facility: Investigational Site Number : 7100005
city: Cape Town
country: South Africa
facility: Investigational Site Number : 7100001
city: Durban
country: South Africa
facility: Investigational Site Number : 7100003
city: George
country: South Africa
facility: Investigational Site Number : 7100006
city: Johannesburg
country: South Africa
facility: Investigational Site Number : 7100008
city: Middelburg
country: South Africa
facility: Investigational Site Number : 7100004
city: Istanbul
country: Turkey
facility: Investigational Site Number : 7920001
city: Izmir
country: Turkey
facility: Investigational Site Number : 7920003
city: Kayseri
country: Turkey
facility: Investigational Site Number : 7920008
city: Kocaeli
country: Turkey
facility: Investigational Site Number : 7920005
city: Mersin
country: Turkey
facility: Investigational Site Number : 7920002
city: Bradford
country: United Kingdom
facility: Investigational Site Number : 8260001
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: