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HOCM, Hypertrophic Obstructive CardiomyopathyPhase 3VALOR-HCMNCT04349072

A Study to Evaluate Mavacamten in Adults With Symptomatic Obstructive HCM Who Are Eligible for Septal Reduction Therapy

A Phase 3 study testing Mavacamten in people with HOCM, Hypertrophic Obstructive Cardiomyopathy, run by Bristol-Myers Squibb at 21 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is a randomized, double-blind, placebo-controlled, multi-center study in the United States (U.S.) that will evaluate the effect of mavacamten treatment on reducing the number of septal reduction therapy (SRT) procedures performed in subjects with symptomatic obstructive hypertrophic cardiomyopathy (oHCM [also… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Mavacamten
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
112 participants
Where
21 sitesUnited States
Study dates
6 Jul 2020to 20 May 2024
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • At least 18 years old at screening and body weight > 45 kg at screening
  • Diagnosed with oHCM consistent with current ACCF/AHA 2011 and meet their recommendations for invasive therapies
  • Referred or under active consideration within the past 12 months for SRT procedure and willing to have SRT procedure
  • Has documented left ventricular ejection fraction (LVEF) ≥ 60% at Screening
  • Has documented oxygen saturation at rest ≥ 90% at Screening

Who cannot join

  • Persistent or permanent atrial fibrillation and subject not on anticoagulation for ≥ 4 weeks prior to screening and/or not adequately rate controlled ≤ 6 months prior to screening
  • Previously treated with invasive septal reduction (surgical myectomy or percutaneous alcohol septal ablation [ASA])
  • For individuals on beta blockers, calcium channel blockers, or disopyramide, any dose adjustment of these medications < 14 days prior to screening or an anticipated change in regimen during the first 16 weeks of the study
  • Any medical condition that precludes upright exercise stress testing
  • Paroxysmal, intermittent atrial fibrillation with atrial fibrillation present at screening
  • Prior treatment with cardiotoxic agents, such as doxorubicin or similar
  • Has a history or evidence of any other clinically significant disorder, condition, or disease that would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion

Trial locations and contacts

21 sites in 1 country.

21 sites in 1 country

United States21 sites

  • Local Institution - 0006

    Ann Arbor, Michigan, 48109

  • Local Institution - 0016

    Boston, Massachusetts, 02114-2696

  • Local Institution - 0007

    Boston, Massachusetts, 02115

  • Local Institution - 0020

    Cleveland, Ohio, 44195

  • Local Institution - 0004

    Durham, North Carolina, 27710

  • Local Institution - 0013

    Grand Rapids, Michigan, 49503

  • Local Institution

    Houston, Texas, 77030

  • Local Institution - 0009

    Los Angeles, California, 90027

  • Local Institution - 0012

    Murray, Utah, 84107-5701

  • Local Institution - 0014

    Nashville, Tennessee, 37205

  • Local Institution - 0018

    Nashville, Tennessee, 37235

  • Local Institution - 0001

    New Haven, Connecticut, 06520

  • Local Institution - 0010

    New York, New York, 10016

  • Local Institution - 0003

    Philadelphia, Pennsylvania, 19104

  • Local Institution - 0019

    Pittsburgh, Pennsylvania, 15212

  • Local Institution - 0002

    Portland, Oregon, 97239

  • Local Institution - 0015

    Rochester, Minnesota, 55905

  • Local Institution - 0005

    St Louis, Missouri, 63110

  • Local Institution - 0011

    Stanford, California, 94305 5406

  • Local Institution - 0017

    Valhalla, New York, 10595

  • Local Institution - 0021

    Weston, Florida, 33331

Other trials in United States

About this study

Official title: A Randomized, Double-blind, Placebo-controlled Study to Evaluate Mavacamten in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy Who Are Eligible for Septal Reduction Therapy

This is a randomized, double-blind, placebo-controlled, multi-center study in the United States (U.S.) that will evaluate the effect of mavacamten treatment on reducing the number of septal reduction therapy (SRT) procedures performed in subjects with symptomatic obstructive hypertrophic cardiomyopathy (oHCM [also known as HOCM]) who are eligible for SRT based on ACCF/AHA 2011 and/or ESC 2014 guidelines.

Being tested
Mavacamten, Placebo
Medical subject headings
Cardiomyopathy, Hypertrophic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MavacamtenDrug

    Mavacamten Capsules Other names: MYK-461

  • PlaceboDrug

    Placebo

Study groups in NCT04349072
Study groupRoleWhat they receive
Drug: MavacamtenExperimentalMavacamten Capsules Other names: MYK-461
Receives: Drug: Mavacamten
Drug: PlaceboPlacebo comparatorMatching Placebo Capsules
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Composite of Decision to Proceed With Septal Reduction Therapy (SRT) and SRT Guideline Eligible at Week 16

    Participants who decided to proceed with SRT or were eligible for SRT at week 16. Participants with missing assessments were classified as meeting the primary endpoint (did not improve).

    SRT eligibility using the New York Heart Association Functional Class (NYHA) and left ventricular outflow tract (LVOT) assessments per the 2011 ACCF/AHA guideline clinical and hemodynamic criterion are below:

    • NYHA Class III or IV/ NYHA Class II with exertion-induced syncope/near syncope, AND
    • Dynamic LVOT gradient at rest or with provocation >= 50 mmHg.

    NYHA Class II at week 16, the following rules will be applied:

    • NYHA Class II with history of exertional syncope/ syncope at baseline and at W16 is still NYHA Class II, they remain SRT eligible IF their maximal LVOT gradient is ≥ 50mmHg
    • NYHA Class III/IV at baseline and at W16 has improved to Class II, they are no longer SRT eligible UNLESS they have AE of exertional syncope or pre-syncope during the 16 weeks.

    Measured: Week 16

Secondary outcomes (5)

  1. Number of Participants With at Least One Class Improvement From Baseline in New York Heart Association (NYHA) Class at Week 16

    The NYHA functional classification of heart failure assigns participants to 1 of 4 categories based on the participants symptoms. Baseline values are defined generally as the last available value before the first administration of study drug of analysis interest. Participants with missing NYHA class assessments are treated as no improvement.

    Class 1: No limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, dyspnea (shortness of breath).

    Class 2: Slight limitation of physical activity. Comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea (shortness of breath).

    Class 3: Marked limitation of physical activity. Comfortable at rest. Less-than ordinary-activity causes fatigue, palpitation, or dyspnea. Class 4: Unable to carry on any physical activity without discomfort. Symptoms of heart failure at rest. If any physical activity is undertaken, discomfort increases.

    Measured: Baseline and week 16

  2. Change From Baseline to Week 16 in Kansas City Cardiomyopathy Questionnaire 23-item Version, Clinical Summary Score (KCCQ-23, CSS)

    The KCCQ-23 is a 23-item, self-administered questionnaire that measures the impact of a participant's cardiovascular disease or its treatment on 6 distinct domains using a 2-week recall period: symptoms/signs, physical limitation, quality of life (QoL), social limitations, self-efficacy, and symptom stability. The KCCQ 23 Clinical Summary Score (CSS) is derived from the Total Symptom Score (TSS) and the Physical Limitations (PL) score of the KCCQ 23. The CSS, TSS, and the PL score range from 0 to 100 with higher scores representing less severe symptoms and/or physical limitations. The CSS is a mean of the TSS and the PL score.

    Measured: Baseline and week 16

  3. Change From Baseline to Week 16 in N-Terminal Pro-b-Type Natriuretic Peptide (NT-proBNP)

    A geometric mean ratio was used to assess the change from baseline to Week 16 in N-Terminal Pro-b-Type Natriuretic Peptide (NT-proBNP). Baseline values are defined as the last non-missing value prior to the first dose of study drug unless specified otherwise.

    Measured: Baseline and week 16

  4. Change From Baseline to Week 16 in Cardiac Troponin

    A geometric mean ratio was used to assess the change from baseline to week 16 in cardiac troponin. Baseline values are defined as the last non-missing value prior to the first dose of study drug unless specified otherwise.

    Measured: Baseline and week 16

  5. Change From Baseline to Week 16 in Post-Exercise Left Ventricular Outflow Tract (LVOT) Gradient

    Change from baseline to week 16 in post-exercise left ventricular outflow tract (LVOT) gradient. Baseline values are defined as the last non-missing value prior to the first dose of study drug unless specified otherwise.

    Measured: Baseline and week 16

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Apr 2020
  2. Study start6 Jul 2020
  3. Primary completion7 Feb 2022
  4. Study completion20 May 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
This is a parallel group treatment study with 2 treatment groups; subjects and investigators are blinded to treatment and dose for the first 16 weeks of treatment. Mavacamten dose is blinded throughout the study.
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
112 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04349072
Sponsor's protocol ID
CV027-006
Acronym
VALOR-HCM
Status last verified
May 2025
First submitted
7 Apr 2020
Last updated
23 May 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Olivotto I, Garcia-Pavia P, Tian Z, Owens AT, Lakdawala NK MD, Balaratnam G, Zhong Y, Memaj A, Barrett YC, Desai M. Mavacamten monotherapy in obstructive hypertrophic cardiomyopathy: An integrated analysis of phase 3 clinical trials. Am Heart J. 2026 Aug 24;303:107587. doi: 10.1016/j.ahj.2026.107587. Online ahead of print.

    PubMed 42636950

  • Desai MY, Wolski K, Owens A, Geske JB, Saberi S, Wang A, Sherrid M, Cremer PC, Lakdawala NK, Tower-Rader A, Fermin D, Naidu SS, Smedira NG, Schaff H, Gong Z, Mudarris L, Lampl K, Sehnert AJ, Nissen SE; VALOR-HCM Investigators. Mavacamten in Patients With Hypertrophic Cardiomyopathy Referred for Septal Reduction: Week 128 Results From VALOR-HCM. Circulation. 2025 May 13;151(19):1378-1390. doi: 10.1161/CIRCULATIONAHA.124.072445. Epub 2024 Nov 18.

    PubMed 39556124

  • Desai MY, Okushi Y, Wolski K, Geske JB, Owens A, Saberi S, Wang A, Cremer PC, Sherrid M, Lakdawala NK, Tower-Rader A, Fermin D, Naidu SS, Lampl KL, Sehnert AJ, Nissen SE, Popovic ZB; VALOR-HCM Investigators. Mavacamten-Associated Temporal Changes in Left Atrial Function in Obstructive HCM: Insights From the VALOR-HCM Trial. JACC Cardiovasc Imaging. 2025 Mar;18(3):251-262. doi: 10.1016/j.jcmg.2024.08.005. Epub 2024 Sep 2.

    PubMed 39254622

  • Desai MY, Okushi Y, Gaballa A, Wang Q, Geske JB, Owens AT, Saberi S, Wang A, Cremer PC, Sherrid M, Lakdawala NK, Tower-Rader A, Fermin D, Naidu SS, Lampl KL, Sehnert AJ, Nissen SE, Popovic ZB; VALOR-HCM Investigators. Serial Changes in Ventricular Strain in Symptomatic Obstructive Hypertrophic Cardiomyopathy Treated With Mavacamten: Insights From the VALOR-HCM Trial. Circ Cardiovasc Imaging. 2024 Sep;17(9):e017185. doi: 10.1161/CIRCIMAGING.124.017185. Epub 2024 Sep 2.

    PubMed 39221824

  • Desai MY, Owens A, Wolski K, Geske JB, Saberi S, Wang A, Sherrid M, Cremer PC, Lakdawala NK, Tower-Rader A, Fermin D, Naidu SS, Smedira NG, Schaff H, McErlean E, Sewell C, Mudarris L, Gong Z, Lampl K, Sehnert AJ, Nissen SE. Mavacamten in Patients With Hypertrophic Cardiomyopathy Referred for Septal Reduction: Week 56 Results From the VALOR-HCM Randomized Clinical Trial. JAMA Cardiol. 2023 Oct 1;8(10):968-977. doi: 10.1001/jamacardio.2023.3342.

    PubMed 37639243

  • Cremer PC, Geske JB, Owens A, Jaber WA, Harb SC, Saberi S, Wang A, Sherrid M, Naidu SS, Schaff H, Smedira NG, Wang Q, Wolski K, Lampl KL, Sehnert AJ, Nissen SE, Desai MY. Myosin Inhibition and Left Ventricular Diastolic Function in Patients With Obstructive Hypertrophic Cardiomyopathy Referred for Septal Reduction Therapy: Insights From the VALOR-HCM Study. Circ Cardiovasc Imaging. 2022 Dec;15(12):e014986. doi: 10.1161/CIRCIMAGING.122.014986. Epub 2022 Nov 6.

    PubMed 36335645

  • Desai MY, Owens A, Geske JB, Wolski K, Saberi S, Wang A, Sherrid M, Cremer PC, Naidu SS, Smedira NG, Schaff H, McErlean E, Sewell C, Balasubramanyam A, Lampl K, Sehnert AJ, Nissen SE. Dose-Blinded Myosin Inhibition in Patients With Obstructive Hypertrophic Cardiomyopathy Referred for Septal Reduction Therapy: Outcomes Through 32 Weeks. Circulation. 2023 Mar 14;147(11):850-863. doi: 10.1161/CIRCULATIONAHA.122.062534. Epub 2022 Nov 6.

    PubMed 36335531

  • Desai MY, Owens A, Geske JB, Wolski K, Naidu SS, Smedira NG, Cremer PC, Schaff H, McErlean E, Sewell C, Li W, Sterling L, Lampl K, Edelberg JM, Sehnert AJ, Nissen SE. Myosin Inhibition in Patients With Obstructive Hypertrophic Cardiomyopathy Referred for Septal Reduction Therapy. J Am Coll Cardiol. 2022 Jul 12;80(2):95-108. doi: 10.1016/j.jacc.2022.04.048.

    PubMed 35798455

  • Zampieri M, Argiro A, Marchi A, Berteotti M, Targetti M, Fornaro A, Tomberli A, Stefano P, Marchionni N, Olivotto I. Mavacamten, a Novel Therapeutic Strategy for Obstructive Hypertrophic Cardiomyopathy. Curr Cardiol Rep. 2021 Jun 3;23(7):79. doi: 10.1007/s11886-021-01508-0.

    PubMed 34081217

  • Desai MY, Wolski K, Owens A, Naidu SS, Geske JB, Smedira NG, Schaff H, Lampl K, McErlean E, Sewell C, Zhang D, Edelberg JM, Sehnert AJ, Nissen SE. Study design and rationale of VALOR-HCM: evaluation of mavacamten in adults with symptomatic obstructive hypertrophic cardiomyopathy who are eligible for septal reduction therapy. Am Heart J. 2021 Sep;239:80-89. doi: 10.1016/j.ahj.2021.05.007. Epub 2021 May 24.

    PubMed 34038706

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Mavacamten in people with HOCM, Hypertrophic Obstructive Cardiomyopathy, run by Bristol-Myers Squibb at 21 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 May 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 21 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Mar 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Composite of Decision to Proceed With Septal Reduction Therapy (SRT) and SRT Guideline Eligible at Week 16 (time frame: Week 16). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04349072, which also lists 10 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 May 2025.

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