Asthma MedDRA version: 20.0 Level: SOC Classification code 10038738 Term: Respiratory, thoracic and mediastinal disorders System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Sponsors
Sanofi aventis recherche et developpement
Eligibility
Sex/Gender
All
Inclusion criteria
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% but =85% 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 criteria within 12 months prior to Visit 1 or documented positive response to methacholine challenge (a decrease in FEV by 20% [PC20] of =65 years) yes F.1.3.1 Number of subjects for this age range 13
Exclusion criteria
Exclusion criteria: - History of serious infections requiring intravenous therapy with the potential for recurrence or currently active moderate to severe infection at Screening (Grade 2 or higher) including active coronavirus disease 2019 (COVID-19). - 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 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. - 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 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 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • Evaluate the effects of rilzabrutinib compared to placebo on reducing the incidence of “loss of asthma control” (LOAC) events;Secondary Objective: • Evaluate the effects of rilzabrutinib compared to placebo on lung function as measured by FEV1 • Assess the effects of rilzabrutinib on other elements of spirometric lung function • Assess the effect of rilzabrutinib on patient reported outcomes • Assess the effects of rilzabrutinib on asthma symptoms • Assess the plasma pharmacokinetic (PK) of rilzabrutinib in participants with asthma • Assess the safety of rilzabrutinib in participants with asthma • Assess the effects of rilzabrutinib on use of bronchodilator therapy;Primary end point(s): Proportion of participants with an LOAC event during the treatment period ; Loss of Asthma Control (LOAC) event is defined as any of the following: - A 30% or greater reduction from baseline in morning 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;Timepoint(s) of evaluation of this end point: Until Week 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1 - Pre-bronchodilator FEV1 (Forced expiratory volume in one second) change from baseline to EOT (end of treatment) 2 - Post-bronchodilator FEV1 change from baseline to EOT 3 - The absolute change in the percent predicted FEV1 from baseline to EOT (pre- and post-bronchodilator) 4 - Change from baseline in pre- and post-bronchodilator FEV1 and other lung function measurements at each spirometry endpoint ; Other lung function measure includes peak expiratory flow [PEF], forced vital capacity [FVC], and forced expiratory flow [FEF] 25-75%) 5 - Asthma Control Questionnaire-5 (ACQ-5) score change from baseline at EOT and at each assessment time point ; The ACQ-5 is a questionnaire that measures the adequacy of asthma control and any changes in asthma control that may occur spontaneously or as a result of treatment. The ACQ-5 has five questions on the asthma symptoms and patients are asked to recall how their asthma has been during the previous week and to respond on a 7-point scale for each question (0 = no impairment, 6 = maximum impairment). The ACQ-5 score is the mean of the 5 questions and, therefore, between 0 (totally controlled) and 6 (severely uncontrolled). A high score indicates low asthma control. 6 - Asthma Quality of Life Questionnaire with Standardized Activities (AQLQ[S]) Self-administered score change from baseline at EOT and at each assessment time point ; The AQLQ(S) was designed as a self-administered patient reported outcome to measure the functional impairments that are most troublesome to adolescents and adults =12 years of age as a result of their asthma. The instrument is comprised of 32 items, each rated on a 7-point Likert scales from 1 to 7. Higher scores indicate better quality of life. 7 - Change in Asthma Daytime Symptom Diary (ADSD) and Asthma Nighttime Symptom Diary (ANSD) scores from baseline to EOT and each week ; ADSD and ANSD assess asthma severity based on patient self-report of asthma core symptoms, i.e., di | — |
Countries
Argentina, Canada, Chile, Korea, Republic of, Mexico, Poland, Russian Federation, Spain, Ukraine, United Kingdom
Contacts
Public ContactUnidad de Estudios Clínicos
Sanofi-Aventis, S.A
Outcome results
None listed