Refractory or Unexplained Chronic Cough MedDRA version: 21.1 Level: LLT Classification code 10066656 Term: Chronic cough System Organ Class: 100000004855
Conditions
Sponsors
Bellus Health, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Between 18 and 80 years of age inclusive, at the time of signing the informed consent 2. Capable of understanding the written informed consent as described in Appendix 1, Section 10.1.5, which includes compliance with the requirements and restrictions listed in the Informed Consent Form (ICF) and in this protocol, provides signed and witnessed written informed consent, and agrees to comply with protocol requirements including being available for the duration of the study 3. After investigation into potential underlying causes of chronic cough, have a diagnosis of RCC defined as: a) insufficient improvement in cough after treatment for the underlying condition(s) contributing to their cough, OR b) unexplained cough for which an underlying condition has not been determined despite adequate investigation with diagnostic tests and trials of therapy 4. The Eligibility Adjudicator assessment confirms prior to randomization that the participant’s history meets diagnostic criteria for RCC 5. Persistent cough for = 1 year prior to Screening 6. Chest radiograph or computed tomography of the thorax within the last 5 years from Screening and following the onset of chronic cough that does not show any abnormality considered to be significantly contributing to the chronic cough in the opinion of the Investigator 7. Participants must meet the following cough frequency criteria: a) Participants in the Primary Efficacy population must have a 24-hour cough frequency of = 20/h at both Screening and Cough Frequency Baseline (Day -7) visits. The Primary Efficacy population will be approximately 150 participants per treatment arm b) Participants in the Extended Efficacy population will have a 24-hour cough frequency between = 8 and 0 and 0 and < 8 coughs/h at Baseline (Day -7). The exploratory population will enroll up to 25 participants per treatment arm 8. A score of = 40 mm on the CS-VAS at Screening and Baseline (Day 1) 9. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies: i) Not a woman of childbearing potential (WOCBP) as defined in Appendix 5. OR ii) A WOCBP who agrees to follow the contraceptive guidance in Appendix 5 from Screening through the Follow-Up Visit. Note: WOCBP must have a negative serum pregnancy test at Screening and negative urine pregnancy test at Baseline and must use a highly effective contraception method from Screening through the Follow up Visit (highly effective methods of birth control in this study include: combined estrogen and progestogen containing or progestogen-only hormonal contraception associated with inhibition of ovulation, intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, and vasectomized partner) 10. Male participants must agree to use contraception as detailed in Appendix 5 of this protocol from Screening through the Follow-Up Visit and make no donation of sperm from Screening until 3 months after the last dose of study treatment. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64
Exclusion criteria
Exclusion criteria: 1. Current smoker or vaper or current use of tobacco smoke, cannabis smoke, or nicotine vapors 2. Individuals who have given up smoking or vaping within the past 6 months, or those with > 20 pack-year smoking history 3. Diagnosis of chronic obstructive pulmonary disease, bronchiectasis, cystic fibrosis, pulmonary sarcoidosis, idiopathic pulmonary fibrosis, or other significant or progressive airway/respiratory disorder that might affect cough based on clinician assessment 4. History of upper and/or lower respiratory tract infection or significant change in pulmonary status within 28 days of Screening or during Screening or the Single-blind Placebo Run-in 5. Laboratory confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection at Screening or Day -7 6. Medical history of malignancy and treatment completed = 5 years prior to Screening except for adequately treated nonmetastatic cutaneous squamous cell or basal cell carcinoma and/or carcinoma in situ of the cervix 7. History of a diagnosis of drug or alcohol dependency or abuse within the last 3 years, per Investigator assessment, or a positive urine opioid drug screen result at Screening. Stable opioid treatment for non-cough indication is permitted (refer to Appendix 4 of the study protocol) 8. Positive serological test for human immunodeficiency virus, hepatitis B, or hepatitis C. Note: Participants with positive hepatitis B or C serology will have confirmatory testing 9. Previous participation in an investigational study of BLU-5937 For the full list of exclusion criteria please refer to the study protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary efficacy objective is to assess the effect of BLU-5937 on 24-hour cough frequency in an enriched population of adults with refractory chronic cough (including unexplained chronic cough) at 12 weeks; The primary safety objective is to determine the effect of BLU-5937 on adverse events and other safety measures (Safety population).;Secondary Objective: To evaluate the effects of BLU-5937 on other measures of cough frequency and PROs (unless otherwise specified, assessed in both Primary and Overall Efficacy populations).;Primary end point(s): 24-hour cough frequency at Week 12 by a cough monitor in the Primary Efficacy population of participants with Baseline 24-hour cough frequency =20 coughs/h • Incidence of TEAEs and treatment-emergent SAEs over the course of the study • Incidence of treatment-emergent AEMIs including spontaneous taste disturbance AE reporting • Discontinuations due to TEAEs • Changes from Baseline in vital signs, clinical laboratory values, including male reproductive hormones, ECGs, physical examinations over the course of the study • A subgroup of participants will undergo slit lamp with pupil dilation to assess the cornea at Baseline, 3 months, 6 months, and 12 months in up to 180 participants, n = 60 in the 50 mg arm, n = 60 in the 25 mg arm, and n = 60 in the placebo arm);Timepoint(s) of evaluation of this end point: Efficacy primary endpoint - week 12. Safety endpoint - week 2 follow-up visit. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): CS-VAS • Change from Baseline in CS-VAS at Week 4, Week 8, and Week 12 • CS-VAS response (proportion of responders with = 30 mm reduction or = 20 mm reduction from Baseline in CS-VAS score) at Week 4, Week 8, and Week 12 Objective cough frequency recording • 24-hour cough frequency in the Overall Efficacy population (participants with Baseline cough frequency = 8 coughs/h) at Week 12 • 24-hour cough frequency at Week 4 and Week 8 • Awake cough frequency at Week 4, Week 8, and Week 12 • 24-hour cough response (proportion of responders with 30%, 50%, or 70% reduction) at Week 4, Week 8, and Week 12 • Awake cough response (proportion of responders with 30%, 50%, or 70% reduction) at Week 4, Week 8, and Week 12 • Nighttime cough frequency at Week 4, Week 8, and Week 12 LCQ • Change from Baseline in the LCQ total score at Week 4, Week 8, and Week 12 • LCQ response (proportion of responders with = 1.3-point increase from Baseline in total score) at Week 4, Week 8, and Week 12 PGI-C • PGI-C score at Week 4, Week 8, and Week 12 PGI-S • Change from Baseline in PGI-S at Week 4, Week 8, and Week 12 CCD • Change from Baseline in CCD score at Week 4, Week 8, and Week 12 • CCD response (proportion of responders) at Week 4, Week 8, and Week 12;Timepoint(s) of evaluation of this end point: Week 4, Week 8, and Week 12 | — |
Countries
Argentina, Belgium, Canada, Colombia, France, Hungary, India, Israel, Netherlands, Poland, South Africa, Spain, Turkey, United Kingdom, United States
Contacts
Public ContactCatherine Bonuccelli
Bellus Health, Inc.
Outcome results
None listed