Brief Summary
This is a randomized, double-blind, placebo-controlled, parallel-arm, Phase 3 study of BLU-5937 in participants with Refractory Chronic Cough (RCC).
Brief Title
A 52-Week Study of the Efficacy and Safety of BLU-5937 in Adults With Refractory Chronic Cough
Detailed Description
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 12 weeks.
Completion Date
Completion Date Type
Estimated
Conditions
Cough
Refractory Chronic Cough
Eligibility Criteria
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, bronchiectasis, chronic bronchitis, cystic fibrosis, pulmonary sarcoidosis, idiopathic pulmonary fibrosis, uncontrolled asthma, or other significant or progressive airway/respiratory disorder that might affect cough based on clinician assessment
* 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
* 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, bronchiectasis, chronic bronchitis, cystic fibrosis, pulmonary sarcoidosis, idiopathic pulmonary fibrosis, uncontrolled asthma, or other significant or progressive airway/respiratory disorder that might affect cough based on clinician assessment
* 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
Inclusion Criteria
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
* 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
Gender
All
Gender Based
false
Keywords
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms, Respiratory
Cough
Chronic Cough
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
80 Years
Minimum Age
18 Years
NCT Id
NCT05599191
Org Class
Industry
Org Full Name
Bellus Health Inc. - a GSK company
Org Study Id
221850
Overall Status
Active, not recruiting
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
A Phase 3, 52-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 (CALM-1)
Primary Outcomes
Outcome Description
Assessed using an ambulatory cough monitor
Outcome Measure
24-Hour Cough Frequency
Outcome Time Frame
Week 12
Outcome Description
An AE is any untoward medical occurrence in a clinical study participant administered a medicinal product and which does not necessarily have a causal relationship with that product. An SAE is defined as any untoward medical occurrence that, at any dose, meets one or more of the criteria listed: results in death, is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect in the offspring of a study participant; or other situations as per the medical or scientific judgment of the Investigator.
Outcome Measure
Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) up to Week 52
Outcome Time Frame
Up to Week 52
Outcome Description
An AEMI is an event of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring is appropriate. The following are AEMIs for this study: taste disturbance, oral hypoesthesia, oral paresthesia, and new or worsening findings of the cornea.
Outcome Measure
Number of Participants with Adverse Events of Medical Interest (AEMIs) up to Week 52
Outcome Time Frame
Up to Week 52
Outcome Description
An AE is any untoward medical occurrence in a clinical study participant administered a medicinal product and which does not necessarily have a causal relationship with that product. An SAE is defined as any untoward medical occurrence that, at any dose, meets one or more of the criteria listed: results in death, is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect in the offspring of a study participant; or other situations as per the medical or scientific judgment of the Investigator.
Outcome Measure
Number of Participants with Study Treatment Discontinuation due to AEs and SAEs up to Week 52
Outcome Time Frame
Up to Week 52
Outcome Description
An AE is any untoward medical occurrence in a clinical study participant administered a medicinal product and which does not necessarily have a causal relationship with that product. An SAE is defined as any untoward medical occurrence that, at any dose, meets one or more of the criteria listed: results in death, is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect in the offspring of a study participant; or other situations as per the medical or scientific judgment of the Investigator.
Outcome Measure
Number of Participants with AEs and SAEs Leading to Study Withdrawal up to Week 52
Outcome Time Frame
Up to Week 52
Outcome Measure
Change from Baseline in Vital Signs: Systolic and Diastolic Blood Pressure (millimeters of mercury [mm Hg]) at Week 52
Outcome Time Frame
Baseline, Week 52
Outcome Measure
Change from Baseline in Vital Sign: Pulse (beats per minute) at Week 52
Outcome Time Frame
Baseline, Week 52
Outcome Measure
Change from Baseline in Vital Sign: Respiratory Rate (breaths per minute) at Week 52
Outcome Time Frame
Baseline, Week 52
Outcome Measure
Change from Baseline in Vital Sign: Body Temperature (degrees Celsius) at Week 52
Outcome Time Frame
Baseline, Week 52
Outcome Measure
Change from Baseline in Vital Sign: Weight (kilograms [kg]) at Week 52
Outcome Time Frame
Baseline, Week 52
Outcome Measure
Change from Baseline in Male Reproductive Hormone: Total Testosterone (nanomoles per liter [nmol/L]) at Week 52
Outcome Time Frame
Baseline, Week 52
Outcome Measure
Change from Baseline in Male Reproductive Hormones: Follicle-Stimulating Hormone [FSH] and Luteinizing Hormone [LH] (international units per liter [IU/L]) at Week 52
Outcome Time Frame
Baseline, Week 52
Outcome Measure
Change from Baseline in Male Reproductive Hormone: Inhibin B (nanograms per liter [ng/L]) at Week 52
Outcome Time Frame
Baseline, Week 52
Outcome Measure
Change from Baseline in Hematology Parameter: Red Blood Cell (RBC) Count (10^12 cells per liter) at Week 52
Outcome Time Frame
Baseline, Week 52
Outcome Measure
Change from Baseline in Hematology Parameters: Hemoglobin and Mean Corpuscular Hemoglobin Concentration (MCHC) (grams per liter [g/L]) at Week 52
Outcome Time Frame
Baseline, Week 52
Outcome Measure
Change from Baseline in Hematology Parameter: Hematocrit (percentage) at Week 52
Outcome Time Frame
Baseline, Week 52
Outcome Measure
Change from Baseline in Hematology Parameter: Mean Corpuscular Volume (MCV) (femtoliters [fL]) at Week 52
Outcome Time Frame
Baseline, Week 52
Outcome Measure
Change from Baseline in Hematology Parameter: Mean Corpuscular Hemoglobin (MCH) (picograms per cell [pg/cell]) at Week 52
Outcome Time Frame
Baseline, Week 52
Outcome Measure
Change from Baseline in Hematology Parameter: Red Cell Distribution Width (RDW) (percentage) at Week 52
Outcome Time Frame
Baseline, Week 52
Outcome Measure
Change from Baseline in Hematology Parameters: White Blood Cell (WBC) Count (neutrophils, lymphocytes, monocytes, eosinophils, and basophils) and Platelet Count (10^9 cells per liter) at Week 52
Outcome Time Frame
Baseline, Week 52
Outcome Measure
Change from Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma-Glutamyl Transferase (GGT) (units per liter [U/L]) at Week 52
Outcome Time Frame
Baseline, Week 52
Outcome Measure
Change from Baseline in Clinical Chemistry Parameters: Alkaline Phosphatase (ALP) and Creatine Kinase (CK) (international units per liter [IU/L]) at Week 52
Outcome Time Frame
Baseline, Week 52
Outcome Measure
Change from Baseline in Clinical Chemistry Parameters: Total Bilirubin, Direct and Indirect Bilirubin, and Creatinine (micromoles per liter) at Week 52
Outcome Time Frame
Baseline, Week 52
Outcome Measure
Change from Baseline in Clinical Chemistry Parameters: Sodium, Potassium, Chloride, Calcium, Magnesium, Bicarbonate, Glucose, and Blood Urea Nitrogen (BUN) (millimoles per liter [mmol/L]) at Week 52
Outcome Time Frame
Baseline, Week 52
Outcome Measure
Change from Baseline in Clinical Chemistry Parameters: Protein and Albumin (grams per liter [g/L]) at Week 52
Outcome Time Frame
Baseline, Week 52
Outcome Measure
Change from Baseline in Clinical Chemistry Parameter: Estimated Glomerular Filtration Rate (eGFR) (milliliters per minute per 1.73 meters squared [mL/min/1.73 m^2]) at Week 52
Outcome Time Frame
Baseline, Week 52
Outcome Measure
Change from Baseline in Clinical Chemistry Parameters: Prothrombin Time (PT) and Activated Partial Thromboplastin Time (aPTT) (seconds) at Week 52
Outcome Time Frame
Baseline, Week 52
Outcome Measure
Change from Baseline in Electrocardiogram (ECG) Value: Heart Rate (beats per minute) at Week 52
Outcome Time Frame
Baseline, Week 52
Outcome Measure
Change from Baseline in ECG Value: PR Interval, QT Interval, RR Interval, QRS Interval, and Corrected QT Interval Using Fridericia's Formula (QTcF) (milliseconds) at Week 52
Outcome Time Frame
Baseline, Week 52
Secondary Ids
Secondary Id
BUS-P3-01
Secondary Id
2024-513460-26-00
Secondary Outcomes
Outcome Description
Assessed by Cough Severity Visual Analogue Scale \[VAS\] by the participant on a 100 mm visual analogue scale where higher scores indicate greater severity.
Outcome Time Frame
Baseline, Week 12
Outcome Measure
Change from Baseline in Cough Severity Visual Analogue Scale at Week 12
Outcome Description
Assessed by Cough Severity Visual Analogue Scale \[VAS\] by the participant on a 100 mm visual analogue scale where higher scores indicate greater severity.
Outcome Time Frame
Baseline, Week 12
Outcome Measure
Percentage of Participants With Greater than or Equal to (>=) 30 mm Reduction From Baseline in Cough Severity Visual Analogue Scale at Week 12
Outcome Description
Assessed using an ambulatory cough monitor
Outcome Time Frame
Week 12
Outcome Measure
Awake Cough Frequency at Week 12
Outcome Description
Assessed using an ambulatory cough monitor
Outcome Time Frame
Baseline, Week 12
Outcome Measure
Percentage of Participants With >= 30 percent (%) Reduction From Baseline in 24-Hour Cough Frequency at Week 12
Outcome Description
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.
Outcome Time Frame
Baseline, Week 12
Outcome Measure
Change from Baseline in the Leicester Cough Questionnaire (LCQ) Total Score at Week 12
Outcome Description
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.
Outcome Time Frame
Baseline, Week 12
Outcome Measure
Percentage of Participants With a >= 1.3-point Increase From Baseline in Leicester Cough Questionnaire (LCQ) Total Score at Week 12
Outcome Description
The CCD is a participant-completed daily diary used to assess chronic cough. The CCD score ranges from 0 to 16, with a higher score indicating worse symptoms.
Outcome Time Frame
Baseline, Week 12
Outcome Measure
Change from Baseline in the Chronic Cough Diary (CCD) Score at Week 12
Outcome Description
Percentage of participants with CCD response will be summarized.
Outcome Time Frame
Week 12
Outcome Measure
Percentage of Participants with CCD Response at Week 12
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
80
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Denisa Ferastraoaru
Investigator Email
dferastr@montefiore.org
Investigator Phone
866-633-8255