A 24-Week Study of the Efficacy and Safety of BLU-5937 in Adults With Refractory Chronic Cough (CALM-2)

Study Overview
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Brief Summary
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This is a randomized, double-blind, placebo-controlled, parallel-arm, Phase 3 study of BLU-5937 in participants with Refractory Chronic Cough (RCC).

Detailed Description
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The primary efficacy objective is to assess the effect of BLU-5937 on 24-hour cough frequency in adults with refractory chronic cough (including unexplained chronic cough) at 24 weeks.

Official Title
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A Phase 3, 24-Week, Randomized, Double-Blind, Placebo-Controlled, Parallel-Arm Efficacy and Safety Study With Open-Label Extension of BLU-5937 in Adult Participants With Refractory Chronic Cough, Including Unexplained 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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BLU-5937 25 mg<br>BLU-5937 oral dose 25 mg twice a day. | Drug: BLU-5937<br>* Oral administration of BLU-5937 Tablets<br>|
| Experimental: BLU-5937 50 mg<br>BLU-5937 oral dose 50 mg 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>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 24-Hour Cough Frequency | Assessed using an ambulatory cough monitor | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Cough Severity Visual Analogue Scale at Week 24 | Assessed by Cough Severity Visual Analogue Scale [VAS] by the participant on a 100 mm visual analog scale where higher scores indicate greater severity. | Baseline, Week 24 | 
| Percentage of Participants With ≥ 30mm Reduction, ≥ 20mm Reduction From Baseline in Cough Severity Visual Analog Scale (VAS) at Week 24 | Assessed by Cough Severity Visual Analogue Scale [VAS] by the participant on a 100 mm visual analog scale where higher scores indicate greater severity. | Baseline, Week 24 | 
| Percentage of Participants With ≥30%, ≥50%, and ≥70% Reduction From Baseline in 24-Hour Cough Frequency at Week 24 | Assessed using an ambulatory cough monitor | Baseline, Week 24 | 
| Change from Baseline in the Leicester Cough Questionnaire (LCQ) Total Score at Week 24 | 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 impact of cough on 3 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. | Baseline, Week 24 | 
| Percentage of Participants With a ≥1.3-point Increase From Baseline in Leicester Cough Questionnaire (LCQ) Total Score at Week 24 | 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 impact of cough on 3 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. | Baseline, Week 24 |