Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43874   clinical trials with a EudraCT protocol, of which   7294   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2022-000188-38
    Sponsor's Protocol Code Number:BUS-P3-02
    National Competent Authority:Slovakia - SIDC (Slovak)
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2022-10-29
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedSlovakia - SIDC (Slovak)
    A.2EudraCT number2022-000188-38
    A.3Full title of the trial
    A Phase 3, 24-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-2)
    24-týždňové, randomizované, dvojito zaslepené, placebom kontrolované klinické skúšanie fázy 3 s paralelným ramenom na vyhodnotenie účinnosti a bezpečnosti BLU-5937 s otvoreným predĺžením u dospelých účastníkov s refraktérnym chronickým kašľom vrátane nevysvetleného chronického kašľa (CALM-2)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Phase 3, 24-Week, Randomized, Efficacy and Safety Study with Open-label Extension of BLU-5937 in Adult Participants with Refractory or Unexplained Chronic Cough
    A.3.2Name or abbreviated title of the trial where available
    CALM-2
    A.4.1Sponsor's protocol code numberBUS-P3-02
    A.5.4Other Identifiers
    Name:INDNumber:142905
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorBellus Health, Inc.
    B.1.3.4CountryCanada
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportBellus Health, Inc.
    B.4.2CountryCanada
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationGlaxoSmithKline Research & Development Ltd.
    B.5.2Functional name of contact pointEU GSK Clinical Trials-Call Center
    B.5.3 Address:
    B.5.3.1Street Address980 Great West Road
    B.5.3.2Town/ cityBrentford, Middlesex
    B.5.3.3Post codeTW8 9GS
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number+442089904466
    B.5.6E-mailGSKClinicalSupportHD@gsk.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameBLU-5937
    D.3.2Product code BLU-5937
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNMethyl (S)-2-((2-(2,6-difluoro-4-(methylcarbamoyl)phenyl)-7-methylimidazo[1,2- a]pyridin-3- yl)methyl)morpholine-4-carboxylate
    D.3.9.1CAS number 1621164-74-6
    D.3.9.2Current sponsor codeBLU-5937
    D.3.9.3Other descriptive nameBLU-5937
    D.3.9.4EV Substance CodeSUB259127
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameBLU-5937
    D.3.2Product code BLU-5937
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNMethyl (S)-2-((2-(2,6-difluoro-4-(methylcarbamoyl)phenyl)-7-methylimidazo[1,2- a]pyridin-3- yl)methyl)morpholine-4-carboxylate
    D.3.9.1CAS number 1621164-74-6
    D.3.9.2Current sponsor codeBLU-5937
    D.3.9.3Other descriptive nameBLU-5937
    D.3.9.4EV Substance CodeSUB259127
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboFilm-coated tablet
    D.8.4Route of administration of the placeboOral use
    D.8 Placebo: 2
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboFilm-coated tablet
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Refractory or Unexplained Chronic Cough
    E.1.1.1Medical condition in easily understood language
    Chronic Cough
    E.1.1.2Therapeutic area Diseases [C] - Respiratory Tract Diseases [C08]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level LLT
    E.1.2Classification code 10066656
    E.1.2Term Chronic cough
    E.1.2System Organ Class 10038738 - Respiratory, thoracic and mediastinal disorders
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To assess the effect of BLU-5937 vs placebo on 24-hour cough frequency in adults with RCC (including unexplained chronic cough) and Baseline 24-hour cough frequency ≥8 coughs/h at Week 24.
    To determine the safety of BLU-5937 vs placebo in adults with RCC (including unexplained chronic cough) up to Week 24.
    E.2.2Secondary objectives of the trial
    To evaluate the effects of BLU-5937 on other measures of cough frequency and PROs.
    E.2.3Trial contains a sub-study No
    E.3Principal 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, 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 24-hour 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 24-hour 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).
    OR
    ii) A WOCBP who agrees to follow the 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, vasectomized partner or same sex partner) or agrees to total abstinence, defined as refraining from heterosexual intercourse, as the preferred and usual lifestyle.
    E.4Principal 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, 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
    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(HIV), hepatitis B, or hepatitis C at Screening
    Notes:
    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.
    E.5 End points
    E.5.1Primary end point(s)
    24-hour cough frequency at Week 24 by a cough monitor in adult participants

    • Incidence of AEs and SAEs up to Week 24
    • Incidence of AEMIs up to Week 24
    • Incidence of study treatment discontinuations due to AEs and SAEs leading to study withdrawal up to Week 24
    • Changes from Baseline in vital signs(systolic and diastolic blood pressure, heart rate, respiratory rate, body temperature, weight) at Week 24, clinical laboratory values (including male reproductive hormones, haematological, and clinical chemistry parameters) at Week 24
    • Changes from Baseline in ECG values at Week 24
    E.5.1.1Timepoint(s) of evaluation of this end point
    Efficacy primary endpoint - Week 24. Safety endpoint - week 2 follow-up visit.
    E.5.2Secondary end point(s)
    CS-VAS
    • Change from Baseline in CS-VAS at Week 24
    • CS-VAS response (achieving ≥ 30 mm reduction or ≥ 20 mm reduction from Baseline in CS-VAS score) at Week 24

    Objective cough frequency recording
    • Awake cough frequency at Week 24
    • 24-hour cough response (achieving 30% reduction) from Baseline at Week 24
    Week 4, Week 8, Week 12, Week 16, Week 20, and Week 24

    LCQ
    • Change from Baseline in the LCQ total score at Week 24
    • LCQ response (achieving ≥ 1.3-point increase from Baseline in total score) at Week 24

    CCD
    • Change from Baseline in CCD score (24-hour symptom scale) at Week 24
    • CCD response (achieving ≥MCIDc improvement from Baseline, 24-hour symptom scale) at Week 24
    E.5.2.1Timepoint(s) of evaluation of this end point
    Week 24
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other Yes
    E.8.1.7.1Other trial design description
    double-blind treatment preceded by single-blind run-in and followed by open-label extension
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial3
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned7
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA23
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    New Zealand
    Taiwan
    Australia
    India
    Korea, Republic of
    United Kingdom
    United States
    Czechia
    Germany
    Slovakia
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned days6
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months6
    E.8.9.2In all countries concerned by the trial days6
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 504
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 321
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state42
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 182
    F.4.2.2In the whole clinical trial 825
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    After a participant has completed the study or has withdrawn prematurely, availability of study treatment for that participant will end. Standard of care treatment should be administered, if required, in accordance with the study site’s standard of care and generally accepted medical practice and depending on the participant’s individual medical needs.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2023-02-09
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2023-01-25
    P. End of Trial
    P.End of Trial StatusOngoing
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Fri May 17 11:08:59 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA