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)

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, bilateral tubal occlusion, vasectomized partner or
same sex partner) or agrees to total abstinence,
defined as refraining from heterosexual intercourse, as the preferred
and usual lifestyle.) 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.

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.