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ODYSSEY_HCM: A Study of Mavacamten in Non-Obstructive Hypertrophic Cardiomyopathy

Sponsor
Bristol-Myers Squibb (Industry)
Overall Status
Not yet recruiting
CT.gov ID
NCT05582395
Collaborator
(none)
420
Enrollment
73
Locations
2
Arms
29
Anticipated Duration (Months)
5.8
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety, tolerability, and efficacy of mavacamten compared with placebo in participants with symptomatic non-obstructive hypertrophic cardiomyopathy (nHCM).

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Anticipated Enrollment :
420 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Randomized, Double-blind, Placebo-controlled Clinical Study to Evaluate Mavacamten in Adults With Symptomatic Non-obstructive Hypertrophic Cardiomyopathy
Anticipated Study Start Date :
Oct 31, 2022
Anticipated Primary Completion Date :
Mar 31, 2025
Anticipated Study Completion Date :
Mar 31, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: Mavacamten

Drug: Mavacamten
Specified dose on specified days
Other Names:
  • BMS-986427
  • MYK-461

    		•
    Placebo Comparator: Placebo

    Other: Placebo
    Specified dose on specified days

    Outcome Measures

    Primary Outcome Measures

    1. Change from baseline in Kansas City Cardiomyopathy Questionnaire (23-item) Clinical Summary Score (KCCQ-23 CSS) at Week 52 [Up to Week 52]

    2. Change from baseline in peak oxygen consumption (pVO2) at Week 52 [Up to Week 52]

    Secondary Outcome Measures

    1. Change from baseline in ventilatory efficiency (VE/VCO2) slope to Week 52 [Up to Week 52]

    2. Proportion of participants with at least 1 class of New York Heart Association (NYHA) improvement from baseline to Week 52 [Up to Week 52]

    3. Proportion of participants with (1) pVO2 ≥ 1.5 milliliter per kilogram per minute (mL/kg/min) and NYHA improvement ≥ 1; or (2) pVO2 ≥ 3 mL/kg/min and NYHA no worsening, from baseline to Week 52 [Up to Week 52]

    4. Change from baseline in N-terminal pro B-type natriuretic peptide (NT-proBNP) to Week 52 [Up to Week 52]

    5. Change from baseline in cardiac troponin-T (cTn-T) to Week 52 [Up to Week 52]

    6. Change from baseline in hypertrophic cardiomyopathy symptom questionnaire-shortness of breath (HCMSQ-SoB) domain to Week 52 [Up to Week 52]

    7. Time to first major adverse cardiovascular events (MACE)-plus events defined as any cardiovascular (CV) death, nonfatal myocardial infarction, non-fatal stroke, hospitalization for heart failure, or hospitalization for arrhythmias [Up to 124 Weeks]

    8. Change from baseline in peak exercise time to Week 52 [Up to Week 52]

    9. Change from baseline in the Borg index measured by cardiopulmonary exercise testing (CPET) to Week 52 [Up to Week 52]

    10. Change from baseline in echocardiographic measures of diastolic function at Week 52: E/A [Up to Week 52]

    11. Change from baseline in echocardiographic measures of diastolic function at Week 52: average medial E/e' [Up to Week 52]

    12. Change from baseline in echocardiographic measures of diastolic function at Week 52: average lateral E/e' [Up to Week 52]

    13. Change from baseline in echocardiographic measures of diastolic function at Week 52: left atrial volume index (LAVI) [Up to Week 52]

    14. Change from baseline to Week 52 in EuroQol-5 Dimension (EQ-5D) scores (Index) [Up to Week 52]

    15. Change from baseline to Week 52 in EQ-5D scores (visual analogue scale [VAS]) [Up to Week 52]

    16. Summary of trough plasma concentration by visit (Ctrough) [Up to 124 Weeks]

    17. Concentration-response relationship between MYK-461 Ctrough (ng/mL) and left ventricular ejection fraction (LVEF) [Up to 124 Weeks]

      LVEF (%) will be measured through different levels of MYK-461 ctrough.

    18. Concentration-response relationship between MYK-461 Ctrough (ng/mL) and ratio between early mitral inflow velocity and mitral annular early diastolic velocity (E/e') [Up to 124 Weeks]

      E/e' will be measured through different levels of MYK-461 ctrough.

    19. Concentration-response relationship between MYK-461 Ctrough (ng/mL) and N-terminal pro B-type natriuretic peptide (NT-proBNP) [Up to 124 Weeks]

      NT-proBNP (pg/mL) will be measured through different levels of MYK-461 ctrough.

    20. Concentration-response relationship between MYK-461 Ctrough (ng/mL) and cardiac troponin T (cTn-T) [Up to 124 Weeks]

      cTn-T (ng/mL) will be measured through different levels of MYK-461 ctrough.

    21. Time to all-cause death [Up to 124 Weeks]

    22. Time to CV death [Up to 124 Weeks]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Diagnosis of HCM consistent with current American College of Cardiology
    Foundation/American Heart Association and European Society of Cardiology guidelines:

    unexplained left-ventricular hypertrophy with non-dilated ventricular chambers in the absence of other cardiac or systemic disease which can produce the required magnitude of hypertrophy of a maximal left ventricular (LV) wall thickness ≥ 15 millimeters (mm) (or ≥ 13 mm with positive family history of hypertrophic cardiomyopathy [HCM]) as determined by core laboratory interpretation

    • Peak left ventricular outflow tract (LVOT) pressure gradient < 30 millimeters mercury (mm Hg) at rest and < 50 mm Hg with provocation (Valsalva maneuver and stress echocardiography)

    • New York Heart Association (NYHA) Class II or III

    Exclusion Criteria:

    • Known infiltrative or storage disorder causing cardiac hypertrophy that mimics non-obstructive hypertrophic cardiomyopathy (nHCM) such as Fabry disease, amyloidosis, or Noonan syndrome with LV hypertrophy

    • History of unexplained syncope within 6 months prior to screening

    • History of sustained ventricular tachyarrhythmia (> 30 seconds) within 6 months prior to screening

    Additional inclusion and exclusion criteria apply.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of California San Diego La Jolla California United States 92037-1337
    2 UCSF School of Medicine San Francisco California United States 94143-2204
    3 Harbor UCLA Medical Center Torrance California United States 90509
    4 University of Florida Gainesville Florida United States 32610
    5 Indiana University School of Medicine-Indianapolis Indianapolis Indiana United States 46202
    6 University of Kansas Medical Center Kansas City Kansas United States 66160
    7 Brigham and Womens Hospital Boston Massachusetts United States 02215
    8 University of Michigan Ann Arbor Michigan United States 48109
    9 Spectrum Health Grand Rapids Michigan United States 49525-6427
    10 Mayo Clinic - PPDS Rochester Minnesota United States 55905
    11 Saint Luke's Hospital of Kansas City Kansas City Missouri United States 64111
    12 Washington University School of Medicine Saint Louis Missouri United States 63110-1025
    13 University of Nebraska Medical Center Omaha Nebraska United States 681980-7680
    14 North Shore University Hospital-(Manhasset) Manhasset New York United States 11030-3816
    15 Westchester Medical Center Valhalla New York United States 10595-1530
    16 Lancaster General Hospital Lancaster Pennsylvania United States 17604
    17 University of Texas Southwestern Medical Center Dallas Texas United States 75390-7202
    18 Local Institution - 0357 Wagga Wagga New South Wales Australia 2650
    19 Local Institution - 0429 Wien Austria 1090
    20 Local Institution - 0462 Edegem Antwerpen Belgium 2650
    21 Local Institution - 0413 Salvador Bahia Brazil 40170-130
    22 Local Institution - 0437 Fortaleza Ceara Brazil 60430-372
    23 Local Institution - 0438 Brasília Distrito Federal Brazil 70710-140
    24 Local Institution - 0425 Belo Horizonte Minas Gerais Brazil 30110-934
    25 Local Institution - 0432 Belo Horizonte Minas Gerais Brazil 30210-090
    26 Local Institution - 0447 Porto Alegre RIO Grande DO SUL Brazil 90560-030
    27 Local Institution - 0450 Porto Alegre RIO Grande DO SUL Brazil 90620-001
    28 Local Institution - 0430 Bragança Paulista SAO Paulo Brazil 12916-542
    29 Local Institution - 0422 Ribeirão Preto SAO Paulo Brazil 14026-900
    30 Local Institution - 0418 São Paulo SAO Paulo Brazil 04012-909
    31 Local Institution - 0412 São Paulo SAO Paulo Brazil 05403-000
    32 Local Institution - 0446 Rio De Janeiro Brazil 20551-030
    33 Local Institution - 0451 Rio de Janeiro Brazil 22061-080
    34 Local Institution - 0467 Vancouver British Columbia Canada V6E 1M7
    35 Local Institution - 0414 Hamilton Ontario Canada L8L 2X2
    36 Local Institution - 0411 London Ontario Canada N6A 5A5
    37 Local Institution - 0470 Montreal Quebec Canada H1T 1C8
    38 Local Institution - 0428 Aabenraa South Denmark Denmark 6200
    39 Local Institution - 0463 Brest Finistère France 29200
    40 Local Institution - 0440 Regensburg Bayern Germany 93053
    41 Local Institution - 0448 Hannover Niedersachsen Germany 30625
    42 Local Institution - 0439 Bad Oeynhausen Nordrhein-Westfalen Germany 32545
    43 Local Institution - 0420 Mainz Rheinland-Pfalz Germany 55131
    44 Local Institution - 0454 München Germany 80636
    45 Local Institution - 0404 Ulm Germany 89081
    46 Local Institution - 0423 Balatonfüred Veszprém Hungary 8230
    47 Local Institution - 0088 Debrecen Hungary 4032
    48 Local Institution - 0417 Szeged Hungary 6725
    49 Local Institution - 0419 Haifa Israel 3109601
    50 Local Institution - 0427 Petah Tikva Israel 49100
    51 Local Institution - 0474 Fukuoka-Shi Fukuoka Japan 814-0180
    52 Local Institution - 0457 Kanazawa-shi Ishikawa Japan 920-8641
    53 Local Institution - 0453 Tsu-Shi MIE Japan 514-0001
    54 Local Institution - 0456 Sendai-shi Miyagi Japan 980-8574
    55 Local Institution - 0452 Osaka-Shi Osaka Japan 545-0051
    56 Local Institution - 0471 Takatsuki-Shi Osaka Japan 569-8686
    57 Local Institution - 0466 Koto-Ku Tokyo Japan 135-0061
    58 Local Institution - 0405 Osaka Japan 558-8558
    59 Local Institution - 0442 Nijmegen Gelderland Netherlands 6525 GA
    60 Local Institution - 0434 Maastricht Netherlands 6211 LK
    61 Local Institution - 0443 Lørenskog Akershus Norway N-1478
    62 Local Institution - 0473 Trondheim Sør-Trøndelag Norway 7006
    63 Local Institution - 0441 Oslo Norway 0424
    64 Local Institution - 0415 Zabrze Slaskie Poland 41-800
    65 Local Institution - 0416 Lódz Poland 93-338
    66 Local Institution - 0436 Warsaw Poland 04-628
    67 Local Institution - 0036 Zamosc Poland 22-400
    68 Local Institution - 0433 Leiria Portugal 2410-187
    69 Local Institution - 0023 Lisboa Portugal 1500-650
    70 Local Institution - 0421 Madrid Spain 28034
    71 Local Institution - 0445 London Greater London United Kingdom SW3 6NP
    72 Local Institution - 0472 London Middlesex United Kingdom EC1A 7BE
    73 Local Institution - 0407 Birmingham United Kingdom B15 2TH

    Sponsors and Collaborators

    • Bristol-Myers Squibb

    Investigators

    • Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Bristol-Myers Squibb
    ClinicalTrials.gov Identifier:
    NCT05582395
    Other Study ID Numbers:
    • CV027-031
    • 2021-005329-26
    • U1111-1269-8581
    First Posted:
    Oct 17, 2022
    Last Update Posted:
    Oct 26, 2022
    Last Verified:
    Oct 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Bristol-Myers Squibb
    Mavacamten
    non-obstructive HCM
    non-obstructive hypertrophic cardiomyopathy (nHCM)
    Additional relevant MeSH terms:
    Cardiomyopathies
    Cardiomyopathy, Hypertrophic
    Hypertrophy

    Study Results

    No Results Posted as of Oct 26, 2022