NCT05104892已完成2 期
A Randomized, Double-blind, Placebo-controlled, Parallel-group, 12 Week Proof-of-Concept (PoC) Study to Assess the Efficacy, Safety, and Tolerability of Rilzabrutinib in Participants With Moderate-to-severe Asthma Who Are Not Well Controlled on Inhaled Corticosteroid (ICS) Plus Long-acting β2 Adrenergic Agonist (LABA) Therapy
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
- 196
- 试验地点
- 51
- 主要终点
- Proportion of participants with an LOAC event during the treatment period
研究概览
简要总结
This is a parallel, treatment, Phase 2, double-blind, 2 arm, 12-week Proof of Concept (PoC) study with 2 staggered cohorts (2 arms in each cohort) that is designed to assess the efficacy, safety, and tolerability of rilzabrutinib in adult participants (aged 18-70 years) with moderate-to-severe asthma who are not well controlled on ICS/LABA therapy. Study treatment includes investigational medicinal product (IMP) (rilzabrutinib or placebo) added-on to a background therapy of ICS/LABA (fluticasone/salmeterol [non-investigational medicinal product], standardized at screening). Background therapy of ICS/LABA will be withdrawn during the 12week randomized treatment period and resumed at the end of the IMP treatment period, as outlined below:
-
Screening period (4 weeks)
-
Randomized IMP treatment period (12 weeks ± 3 days)
-
Background therapy stabilization phase (4 weeks)
-
Background therapy withdrawal phase (4-5 weeks)
-
No background therapy phase (3-4 weeks)
-
Post IMP treatment safety follow-up period (4 weeks ± 3 days)
详细描述
The total study duration per participant is expected to be up to 20 weeks: up to 4 weeks screening, 12 weeks on-treatment double-blind period, and 4-week post-IMP treatment follow up.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •A physician diagnosis of asthma for at least 12 months based on the Global Initiative for Asthma (GINA) 2018,2019, 2020 Guidelines.
- •Participants with existing treatment with at least moderate to high doses of ICS therapy in combination with a LABA as second controller for at least 3 months with a stable dose ≥1 month prior to Visit
- •Participants with prebronchodilator FEV1 >40% of predicted normal at Visit 1/Screening. Prebronchodilator FEV1 ≥50% of predicted normal at Visit 2/Baseline.
- •Participants with reversibility of at least 12% and 200 mL in FEV1 15 to 30 minutes after administration of 2 to 4 puffs (200-400 mcg) of albuterol/salbutamol or levalbuterol/levosalbutamol during screening or documented history of a reversibility test that meets this criterion within 5 years prior to Visit 1 or documented positive response to methacholine challenge (a decrease in FEV by 20% [PC20] of <8mg/mL) within 5 years prior to Visit 1/Screening is considered acceptable to meet this inclusion criterion.
- •Participants must have experienced, within 2 years prior to Visit 1, any of the following asthma exacerbation events at least once: Treatment with a systemic steroid (oral or parenteral) for worsening asthma OR Hospitalization or emergency medical care visit for worsening asthma.
- •Body mass index (BMI) ≥17.5 and ≤40 kg/m2
- •All Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
- •Participants must have completed COVID-19 vaccination per current regional health authority recommendations prior to screening.
排除标准
- •History of serious infections requiring intravenous therapy with the potential for recurrence (as judged by Site Investigator), with less than 4 weeks interval between resolution of serious infection and first dose of study drug, or currently active moderate-to-severe infection at Screening (Grade 2 or higher).
- •Chronic lung disease (for example, chronic obstructive pulmonary disease [COPD], or idiopathic pulmonary fibrosis [IPF]) which may impair lung function, or another diagnosed pulmonary or systemic disease associated with elevated peripheral eosinophil counts, for e.g. eosinophilic granulomatosis with polyangiitis.
- •History of life-threatening asthma (i.e., severe exacerbation that requires intubation).
- •Participants with any of the following events within the 4 weeks prior to their Screening Visit 1 or during the screening period: Treatment with 1 or more systemic (oral and/or parenteral) steroid bursts for worsening asthma OR Hospitalization or emergency medical care visit for worsening asthma
- •Asthma Control Questionnaire 5-question version (ACQ-5) score <1.25 or >3.0 at V2/randomization. During the screening period an ACQ-5 of up to ≤4 is acceptable.
- •Current smoker or cessation of smoking within the 6 months prior to Visit
- •Previous smoker with a smoking history >10 pack-years.
- •Current or chronic history of liver disease.
- •Known hepatic or biliary abnormalities, e.g. moderate or severe hepatic impairment, such as Child Pugh B or C
- •Symptomatic herpes zoster within 3 months prior to screening.
- •Refractory nausea and vomiting, malabsorption, external biliary shunt, or significant bowel resection that would preclude adequate rilzabrutinib/placebo absorption.
- •Conditions that may predispose the participant to excessive bleeding
- •History of solid organ transplant.
- •A history of malignancy of any type within 5 years before Day 1, other than surgically excised non-melanoma skin cancers or in situ cervical cancer.
- •Is not up-to-date with recommended vaccinations per local guidelines.
- •Anti-immunoglobulin E (IgE) therapy (e.g., omalizumab [Xolair®]) within 130 days prior to Visit 1 or any other biologic therapy (including anti-IL4/4R or IL-5/5R monoclonal antibodies [mAb]) or systemic immunosuppressant (e.g., methotrexate) to treat inflammatory disease or autoimmune disease (e.g., rheumatoid arthritis, inflammatory bowel disease, primary biliary cirrhosis, systemic lupus erythematosus, multiple sclerosis) and other diseases, within 2 months or 5 half-lives prior to Visit 1, whichever is longer.
- •Use of inhalers other than ICSs, LABAs, and short-acting beta agonists (no long-acting muscarinic antagonists (LAMAs) or mucolytics) and leukotriene receptor antagonists (montelukast, zafirkulast) during the study period.
- •Participants who have received bronchial thermoplasty within 2 years prior to Visit 1 or plan to begin therapy during the screening period or the randomized treatment period.
- •Use of proton pump inhibitor drugs such as omeprazole and esomeprazole within 3 days of Day
- •Use of known systemic strong-to-moderate inducers or inhibitors of CYP3A within 14 days or 5 half-lives (whichever is longer) of Study Day 1 and until the end of the active treatment period.
- •Live vaccine except Bacille Calmette Guerinn-vaccination within 28 days prior to Day 1 or plans to receive one during the trial; Calmette Guerin-vaccination within 12 months prior to Screening.
- •COVID-19 vaccine within 14 days prior to Study Day
- •Previous use of a Bruton tyrosine kinase (BTK) inhibitor.
- •Has received any investigational drug (or is currently using an investigational device) within the 30 days before Day 1, or at least 5 times the respective elimination half-life time (whichever is longer).
- •Electrocardiogram (ECG) findings of QT corrected for heart rate (QTc) >450 msec (males) or >470 msec (females), poorly controlled atrial fibrillation (i.e., symptomatic patients or a ventricular rate above 100 beats/min on ECG), or other clinically significant cardiovascular abnormalities.
- •Active COVID-19 infection as documented by a positive COVID-19 molecular test.
- •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
Rilzabrutinib
Experimental
Rilzabrutinib BID or TID and ICS/LABA
干预措施: Rilzabrutinib (Drug)
Placebo
Placebo Comparator
Placebo and ICS/LABA
干预措施: placebo (Drug)
结局指标
主要结局
Proportion of participants with an LOAC event during the treatment period
时间窗: Until Week 12
Loss of Asthma Control (LOAC) event is defined as any of the following: * A 30% or greater reduction from baseline in morning peak expiratory flow (PEF) on 2 consecutive days * ≥6 additional reliever puffs of salbutamol/albuterol or levosalbutamol/levalbuterol in a 24-hour period (compared to baseline) on 2 consecutive days * Increase in ICS ≥4 times the last prescribed ICS dose (or ≥50% of the prescribed ICS dose at V2 if background therapy withdrawal completed) * Requiring use of systemic (oral and/or parenteral) steroid treatment * Requiring hospitalization or emergency room visit for asthma exacerbation
次要结局
- Pre-bronchodilator FEV1 (Forced expiratory volume in one second) change from baseline to EOT (end of treatment)(From baseline to Week 12)
- Post-bronchodilator FEV1 change from baseline to EOT(From baseline to Week 12)
- The absolute change in the percent predicted FEV1 from baseline to EOT (pre- and post-bronchodilator)(From baseline to Week 12)
- Change from baseline in pre- and post-bronchodilator FEV1 and forced vital capacity [FVC] at each spirometry endpoint(From baseline until Week 12)
- Change from baseline in peak expiratory flow [PEF] and forced expiratory flow [FEF] 25-75% at each spirometry endpoint(From baseline until Week 12)
- Asthma Control Questionnaire-5 (ACQ-5) score change from baseline at EOT and at each assessment time point(From baseline until Week 12)
- Asthma Quality of Life Questionnaire with Standardized Activities (AQLQ[S]) Self-administered score change from baseline at EOT and at each assessment time point(From baseline until Week 12)
- Change in Asthma Daytime Symptom Diary (ADSD) and Asthma Nighttime Symptom Diary (ANSD) scores from baseline to EOT and each week(From baseline until Week 12)
- Plasma pharmacokinetic (PK) concentrations of rilzabrutinib in participants with asthma(Until Week 16)
- Change in numbers of inhalations/day of albuterol or levalbuterol for symptom relief from baseline to EOT and each week(From baseline until Week 12)
- Participants with Treatment Emergent Adverse Events(Until Week 16)
研究者
研究点 (51)
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