Dose Ranging Study of Amlitelimab in Adult Participants With Moderate-to-severe Asthma (TIDE-asthma)

Sanofi

Status and phase: Active, not recruiting; Phase 2

Conditions: Asthma

Treatments: Drug: Placebo; Drug: Amlitelimab

Study type: Interventional

Funder types: Industry

Identifiers

NCT05421598

2022-000065-41 (EudraCT Number)

DRI17509

U1111-1272-2612 (Registry Identifier)

Details and patient eligibility

About

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.

Enrollment: 446 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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446 participants in 4 patient groups, including a placebo group

Amlitelimab dose level 1

Experimental group

Description:

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.

Treatment:

Drug: Amlitelimab

Amlitelimab dose level 2

Experimental group

Description:

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.

Treatment:

Drug: Amlitelimab

Amlitelimab dose level 3

Experimental group

Description:

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.

Treatment:

Drug: Amlitelimab

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo