NCT05421598已完成2 期
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
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Sanofi
- 入组人数
- 446
- 试验地点
- 113
- 主要终点
- Annualized rate of severe exacerbation events over 48 weeks
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Amlitelimab dose level 1
Experimental
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.
干预措施: Amlitelimab (Drug)
Amlitelimab dose level 2
Experimental
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.
干预措施: Amlitelimab (Drug)
Amlitelimab dose level 3
Experimental
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.
干预措施: Amlitelimab (Drug)
Placebo
Placebo Comparator
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.
干预措施: Placebo (Drug)
结局指标
主要结局
Annualized rate of severe exacerbation events over 48 weeks
时间窗: 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.
次要结局
- Change from baseline in Asthma Control Questionnaire 5 (ACQ-5) score at Week 48(Baseline to Week 48)
- Change from baseline in pre-bronchodilator (BD) FEV1 at Week 48(Baseline to 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)
- 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)
- 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 forced vital capacity (FVC)(Baseline to Weeks 4, 12, 24, 36, 48 and 60)
- Change from baseline in post-BD FEV1 at Week 48(Baseline to Week 48)
- The absolute change in the percent predicted FEV1 from baseline to Week 48 (pre-BD and post-BD)(Baseline to Week 48)
- Time to first severe exacerbation event(Baseline through Week 48)
- 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)
- Time to first LOAC event(Baseline through Week 48)
- Incidence of anti-amlitelimab antibody positive response(Baseline through Week 60)
- Incidence of potentially clinically significant laboratory test, vital signs, and ECG abnormalities in the treatment period(Baseline through Week 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)
- 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)
- Annualized rate of loss of asthma control (LOAC) events 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(Baseline through Week 48)
- 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)
- Serum amlitelimab concentrations measured throughout the study(Baseline thought Week 60)
- 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)
- Proportion of participants with a decrease from baseline of at least 4 points in SGRQ total score at Week 48(Week 48)
- 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)
- 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)
- 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)
研究者
研究点 (113)
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