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

ACT17208

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 Background therapy of ICS/LABA will be withdrawn during the 12week randomized treatment period and resumed at the end of the IMP treatment period, as outlined below: * Screening period (4 weeks) * Randomized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)

2021-12-12

2024-02-06

2024-02-28

Completed

Early phase I

196

Inclusion Criteria: * 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 1. * 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. Exclusion Criteria: * 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 1. * 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 1. * 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 1. * 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.

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}}, 'enrollmentInfo': {'count': 196, 'type': 'ACTUAL'}}

2024-03-07