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

NCT04349072 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: CV027-006
• Study Type: interventional
• Target: 112
• Locations: 1 country
• Sites: 21

Brief 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 \[also known as HOCM\]) who are eligible for SRT based on ACCF/AHA 2011 and/or ESC 2014 guidelines.

Conditions

HOCM, Hypertrophic Obstructive Cardiomyopathy

Outcome Measures

Primary Outcomes (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.

  Week 16

Secondary Outcomes (5)

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

  Baseline and week 16

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

  Baseline and week 16

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

  Baseline and week 16

• Change From Baseline to Week 16 in Cardiac Troponin

  Baseline and week 16

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

  Baseline and week 16

Study Arms (2)

Drug: Mavacamten

EXPERIMENTAL

Mavacamten Capsules Other names: MYK-461

Drug: Mavacamten

Drug: Placebo

PLACEBO COMPARATOR

Matching Placebo Capsules

Drug: Placebo

Interventions

Mavacamten DRUG

Mavacamten Capsules Other names: MYK-461

Drug: Mavacamten

Placebo DRUG

Placebo

Drug: Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (21)

Local Institution - 0009

Los Angeles, California, 90027, United States

Location

Local Institution - 0011

Stanford, California, 94305 5406, United States

Location

Local Institution - 0001

New Haven, Connecticut, 06520, United States

Location

Local Institution - 0021

Weston, Florida, 33331, United States

Location

Local Institution - 0016

Boston, Massachusetts, 02114-2696, United States

Location

Local Institution - 0007

Boston, Massachusetts, 02115, United States

Location

Local Institution - 0006

Ann Arbor, Michigan, 48109, United States

Location

Local Institution - 0013

Grand Rapids, Michigan, 49503, United States

Location

Local Institution - 0015

Rochester, Minnesota, 55905, United States

Location

Local Institution - 0005

St Louis, Missouri, 63110, United States

Location

Local Institution - 0010

New York, New York, 10016, United States

Location

Local Institution - 0017

Valhalla, New York, 10595, United States

Location

Local Institution - 0004

Durham, North Carolina, 27710, United States

Location

Local Institution - 0020

Cleveland, Ohio, 44195, United States

Location

Local Institution - 0002

Portland, Oregon, 97239, United States

Location

Local Institution - 0003

Philadelphia, Pennsylvania, 19104, United States

Location

Local Institution - 0019

Pittsburgh, Pennsylvania, 15212, United States

Location

Local Institution - 0014

Nashville, Tennessee, 37205, United States

Location

Local Institution - 0018

Nashville, Tennessee, 37235, United States

Location

Local Institution

Houston, Texas, 77030, United States

Location

Local Institution - 0012

Murray, Utah, 84107-5701, United States

Location

Related Publications (9)

• 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.

  PMID: 39556124 DERIVED

• 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.

  PMID: 39254622 DERIVED

• 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.

  PMID: 39221824 DERIVED

• 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.

  PMID: 37639243 DERIVED

• 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.

  PMID: 36335645 DERIVED

• 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.

  PMID: 36335531 DERIVED

• 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.

  PMID: 35798455 DERIVED

• 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.

  PMID: 34081217 DERIVED

• 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.

  PMID: 34038706 DERIVED

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Cardiomyopathy, Hypertrophic

Interventions

MYK-461

Condition Hierarchy (Ancestors)

Cardiomyopathies; Heart Diseases; Cardiovascular Diseases; Aortic Stenosis, Subvalvular; Aortic Valve Stenosis; Aortic Valve Disease; Heart Valve Diseases

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Please email

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: April 7, 2020
• First Posted: April 16, 2020
• Study Start: July 6, 2020
• Primary Completion: February 7, 2022
• Study Completion: May 20, 2024
• Last Updated: May 23, 2025
• Results First Posted: March 7, 2023

Record last verified: 2025-05

Locations

US (21)