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

NCT ID: NCT04349072

Last Updated: 2025-05-23

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

112 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-07-06

Study Completion Date

2024-05-20

Brief Summary

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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.

Detailed Description

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Conditions

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HOCM, Hypertrophic Obstructive Cardiomyopathy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Drug: Mavacamten

Mavacamten Capsules

Other names:

MYK-461

Group Type EXPERIMENTAL

Mavacamten

Intervention Type DRUG

Mavacamten Capsules Other names: MYK-461

Drug: Placebo

Matching Placebo Capsules

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo

Interventions

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Mavacamten

Mavacamten Capsules Other names: MYK-461

Intervention Type DRUG

Placebo

Placebo

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Bristol-Myers Squibb

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Bristol-Myers Squibb

Role: STUDY_DIRECTOR

Bristol-Myers Squibb

Locations

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Local Institution - 0009

Los Angeles, California, United States

Site Status

Local Institution - 0011

Stanford, California, United States

Site Status

Local Institution - 0001

New Haven, Connecticut, United States

Site Status

Local Institution - 0021

Weston, Florida, United States

Site Status

Local Institution - 0016

Boston, Massachusetts, United States

Site Status

Local Institution - 0007

Boston, Massachusetts, United States

Site Status

Local Institution - 0006

Ann Arbor, Michigan, United States

Site Status

Local Institution - 0013

Grand Rapids, Michigan, United States

Site Status

Local Institution - 0015

Rochester, Minnesota, United States

Site Status

Local Institution - 0005

St Louis, Missouri, United States

Site Status

Local Institution - 0010

New York, New York, United States

Site Status

Local Institution - 0017

Valhalla, New York, United States

Site Status

Local Institution - 0004

Durham, North Carolina, United States

Site Status

Local Institution - 0020

Cleveland, Ohio, United States

Site Status

Local Institution - 0002

Portland, Oregon, United States

Site Status

Local Institution - 0003

Philadelphia, Pennsylvania, United States

Site Status

Local Institution - 0019

Pittsburgh, Pennsylvania, United States

Site Status

Local Institution - 0014

Nashville, Tennessee, United States

Site Status

Local Institution - 0018

Nashville, Tennessee, United States

Site Status

Local Institution

Houston, Texas, United States

Site Status

Local Institution - 0012

Murray, Utah, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 39556124 (View on PubMed)

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.

Reference Type DERIVED
PMID: 39254622 (View on PubMed)

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.

Reference Type DERIVED
PMID: 39221824 (View on PubMed)

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.

Reference Type DERIVED
PMID: 37639243 (View on PubMed)

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.

Reference Type DERIVED
PMID: 36335645 (View on PubMed)

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.

Reference Type DERIVED
PMID: 36335531 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35798455 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34081217 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34038706 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

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Other Identifiers

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CV027-006

Identifier Type: -

Identifier Source: org_study_id

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