A Phase 3 Study with Open-Label Extension of BLU-5937 to determine Efficacy and Safety in Adult Participants with Refractory Chronic Cough, Including Unexplained Chronic Cough (CALM-1)
- Conditions
- Health Condition 1: R05- Cough
- Registration Number
- CTRI/2023/06/054278
- Lead Sponsor
- Bellus Health, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Open to Recruitment
- Sex
- Not specified
- Target Recruitment
- 0
Male and female participants are eligible to be included in the study only if all the following criteria apply:
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, which includes compliance with the requirements and restrictions listed in the Informed Consent Form 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 = 1year 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 coughs/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 < 40 coughs/h at Screening and a 24-hour cough frequency between = 8 and < 20 coughs/h at Baseline (Day -7). The Extended Efficacy population will be approximately 50 participants per treatment arm
c) Participants in the Exploratory Efficacy population will have a 24-hour cough frequency between > 0 and < 16 coughs/h at Screening and a 24-hour cough frequency between > 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 Cough Severity Visual Analogue Scale 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:
a) Not a woman of childbearing potential (WOCBP)
OR
b) A WOCBP who agrees to follow the protocol-specified contraceptive guidance 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 protocol-specified contraception from Screening through the Follow
Participants are excluded from the study if any of the following criteria apply:
1.Female participants who are pregnant, trying to become pregnant or lactating
2.Current smoker or vaper, or current use of tobacco smoke, cannabis smoke, or nicotine vapors
3.Individuals who have given up smoking or vaping within the past 6 months, or those with > 20 pack-year smoking history
4.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
5.Uncontrolled asthma, defined as one or both of the following:
a)= 1 clinically significant exacerbation in the last 6 months or = 2 clinically significant exacerbations in the past 12 months. A clinically significant asthma exacerbation is defined as requiring the use of systemic corticosteroids
b)Use of rescue medication = 3 days per week or nighttime awakening > 1 time per week (pre-exercise prophylactic medication use will not be considered rescue medication).
6.Pre-bronchodilator forced expiratory in 1 second (FEV1)/forced vital capacity (FVC) < 60% at Screening or on spirometry testing performed within 2 years before Screening and following the onset of chronic cough
7.Participants who failed to use the cough monitor or who are confirmed to have incorrectly recorded 24-hour cough frequency at Screening or Cough Frequency Baseline (Day -7) Visits. Retest is allowed once only if insufficient recording time is captured and approved by the Medical Monitor. Incorrectly recorded 24-hour cough frequencies are defined as recordings where less than 20 hours of the recording can be assessed for cough frequency
8.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
9.Current active tuberculosis or nontuberculous mycobacterial infection, a history of latent untreated tuberculosis, or a history of incompletely treated tuberculosis
10.Laboratory confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection at Screening or Day -7
11.History of SARS-CoV-2 infection or Coronavirus Disease-2019 (COVID-19) within 3 months of Screening, history of long COVID, or known exposure to someone with SARS-CoV-2 infection or COVID-19 within 10 days of Screening. History of fully resolved long COVID may be permitted after discussion with the Medical Monitor
12.Requiring concomitant therapy with prohibited medications or non-pharmacological therapy
13. Medical history of hypogeusia/dysgeusia/ageusia or known presence of a dysfunction in ability to taste.Participants with a history of taste disturbance that has fully resolved and was due to prior P2X3 antagonist drug exposure or participation in a previous clinical study of P2X3 antagonist or previous SARS-CoV-2 infection will be eligible
14. 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
15. History of a diagnosis of drug or alcohol dependency or abuse within the last 3 years, p
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method •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. <br/ ><br> <br/ ><br>•The primary safety objective is to determine the effect of BLU-5937 on adverse events and other safety measures (Safety population) <br/ ><br>Timepoint: <br/ ><br>•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
- Secondary Outcome Measures
Name Time Method •To evaluate the effects of BLU-5937 on other measures of cough frequency and PROs (unless otherwise specified, assessed in both Primary and <br/ ><br>Overall Efficacy populations) <br/ ><br>Timepoint: Change from Baseline in CS-VAS at Week 4, Week 8, and Week 12