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)
- Conditions
- Chronic CoughRCC10046304
- Registration Number
- NL-OMON56306
- Lead Sponsor
- Bellus Health, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 24
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 Overall Efficacy population must have a 24-hour
cough frequency of >=16 coughs/h at Screening and >=20 coughs/h at
Baseline (Day -7), or between >=8 and <40 coughs/h at Screening and
between >=8 and <20 coughs/h at Baseline (Day -7). Approximately 25%
of participants with a 24-hour cough frequency between >=8 and <40
coughs/h at Screening and between >=8 and <20 coughs/h at Baseline
will be enrolled (approximately 63 participants per treatment arm).
When this 25% threshold has been reached, only participants with a 24hour cough
frequency of >=16 coughs/h at Screening and >=20 coughs/h
at Baseline will be enrolled (approximately 187 participants per treatment arm).
b) Participants in the Exploratory Efficacy population will have a
24-hour
cough frequency between >0 and <16 coughs/h at Screening and a
24hour cough frequency between >0 and <8 coughs/h at Baseline (Day
7). The exploratory population will enroll participants until up to 25 per
treatment arm has been reached.
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 (2 weeks after the last dose of study
drug). 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, b
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, chronic bronchitis,
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 during Single-blind Placebo
Run-in. 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 HIV,
hepatitis B, or hepatitis C at
Screening
Note: Participants with positive hepatitis B or C serology will have
confirmatory testing. Participants with HIV on stable treatment with
undetectable viral load are acceptable if the participant otherwise meets
entry criteria. Participants with positive hepatitis C antibody test due to
prior resolved disease who have successfully completed a course of
antiviral therapy can be enrolled, only if a confirmatory negative
hepatitis C RNA test is obtained and if the participant otherwise meets
entry criteria
9. Previous participation in an investigational study of BLU-5937 For the full
list of exclusion criteria please refer to the study protocol.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>24-hour cough frequency at Week 12 by a cough monitor.<br /><br>• Incidence of AEs and SAEs up to Week 52<br /><br>• Incidence of up to Week 52<br /><br>• Occurrences of study treatment discontinuations due to AEs and SAEs<br /><br>up to Week 52<br /><br>• Occurrences of AEs and SAEs leading to study withdrawal up to Week<br /><br>52<br /><br>• Changes from Baseline in vital signs (systolic and diastolic blood<br /><br>pressure, heart rate, respiratory rate, body temperature, weight) at<br /><br>Week 52<br /><br>• Changes from Baseline in clinical laboratory values, (including male<br /><br>reproductive hormones, hematological and clinical chemistry<br /><br>parameters) at<br /><br>Week 52<br /><br>• Changes from Baseline in ECG values at Week 52</p><br>
- Secondary Outcome Measures
Name Time Method <p>CS-VAS<br /><br>• Change from Baseline in CS-VAS at Week 12<br /><br>• CS-VAS response (achieving >= 30 mm reduction from Baseline in CSVAS score) at<br /><br>Week<br /><br>12<br /><br>Objective cough frequency recording<br /><br>• Awake cough frequency at Week 12<br /><br>• 24-hour cough response (achieving 30% reduction from Baseline) at<br /><br>Week 12<br /><br>LCQ<br /><br>• Change from Baseline in the LCQ total score at Week 12<br /><br>• LCQ response (achieving >= 1.3-point increase from Baseline in total<br /><br>score) at Week 12<br /><br>CCD<br /><br>• Change from Baseline in CCD score(24-hour symptom scale) at Week<br /><br>12<br /><br>• CCD response (achieving >=MCID improvement from Baseline, 24-hour<br /><br>symptom scale)at Week 12</p><br>