Evaluation of the Efficacy and Safety of BLU-5937 in Adults With Refractory Chronic Cough

Study Overview
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Brief Summary
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This is a randomized, double-blind, placebo-controlled, parallel-arm, Phase 2b adaptive dose-finding study of BLU-5937 in participants with Refractory Chronic Cough (RCC).

Detailed Description
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The primary objective of this study is to determine the therapeutic dose of BLU-5937 in patients with refractory chronic cough by assessing the change from baseline to week 4 in the 24-hour cough frequency with BLU-5937 relative to placebo.

Official Title
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A Randomized, Adaptive, Double-Blind, Placebo-Controlled, Parallel-Arm, Phase 2b Study to Evaluate the Efficacy and Safety of Multiple Doses of BLU-5937 in Adult Participants With Refractory Chronic Cough

Conditions
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Refractory Chronic Cough

Intervention / Treatment
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* Drug: BLU-5937
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Capable of giving signed informed consent Refractory chronic cough (including unexplained chronic cough) for at least one year Women of child-bearing potential must use a highly effective contraception method during the study and for at least 14 days after the last dose Exclusion Criteria: Current smoker/vaper (all forms of smoking and inhaled substances, including , cannabis/tobacco smoke and nicotine vapors) or individuals who have given up smoking within the past 6 months, or those with >20 pack-year smoking history Diagnosis of Chronic Obstructive Pulmonary Disease (COPD), bronchiectasis, idiopathic pulmonary fibrosis or uncontrolled asthma Respiratory tract infection within 4 weeks before screening Laboratory confirmed Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection at screening History of malignancy in the last 5 years History of alcohol or drug abuse within the last 3 years Has a positive serologic test for human immunodeficiency virus (HIV), hepatitis B virus surface antigen, or hepatitis C virus. Previous participation in a BLU-5937 trial

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BLU-5937 Dose A<br>BLU-5937 oral dose A twice a day. | Drug: BLU-5937<br>* Oral administration of BLU-5937 Tablets<br>|
| Experimental: BLU-5937 Dose B<br>BLU-5937 oral dose B twice a day. | Drug: BLU-5937<br>* Oral administration of BLU-5937 Tablets<br>|
| Experimental: BLU-5937 Dose C<br>BLU-5937 oral dose C twice a day. | Drug: BLU-5937<br>* Oral administration of BLU-5937 Tablets<br>|
| Placebo Comparator: Placebo<br>Matching Placebo for BLU-5937 oral dose twice a day. | Drug: Placebo<br>* Oral administration of matching placebo for BLU-5937 Tablets<br>|
| Experimental: BLU-5937 Dose A (Population with baseline cough < 25 coughs/hour)<br>BLU-5937 oral dose A twice a day. | Drug: BLU-5937<br>* Oral administration of BLU-5937 Tablets<br>|
| Placebo Comparator: Placebo (Population with baseline cough < 25 coughs/hour)<br>Matching Placebo for BLU-5937 oral dose twice a day. | Drug: Placebo<br>* Oral administration of matching placebo for BLU-5937 Tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in the 24-hour cough frequency | Assessed using an ambulatory cough monitor | Week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with a Reduction from Baseline in the 24-hour Cough Frequency by ≥ 30%, 50% and 70% | Assessed using an ambulatory cough monitor | Week 4 | 
| Change from Baseline in Leicester Cough Questionnaire (LCQ) | The LCQ is a patient-reported quality of life (QOL) measure of chronic cough. The questionnaire consists of 19 items to which the patient responds on a 7-point Likert response scale (from 1 to 7). Each item assesses symptoms during cough and the effect of cough on 3 main domains: physical, psychological and social. Domain scores range from 1-7, and the total score ranges from 3 - 21; a higher score indicates a better quality of life. | Week 4 | 
| Change from baseline in cough severity | Assessed by Cough Severity Visual Analogue Scale [VAS] by the participant on a 100 mm visual analog scale where higher scores indicate worse severity. | Week 4 | 
| Incidence (% of subjects) of treatment-emergent adverse events (TEAEs) |  | 2 Weeks after the last study medication intake | 
| Severity (mild, moderate, or severe) of treatment-emergent adverse events (TEAEs) |  | 2 Weeks after the last study medication intake | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BLU-5937, Refractory Chronic Cough, P2X3 receptor antagonist