Clinical Study to Evaluate Mavacamten (MYK-461) in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy

NCT ID: NCT03470545

Last Updated: 2021-10-04

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

251 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-05-29

Study Completion Date

2020-05-06

Brief Summary

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This is a multicenter, international, double-blind study of the administration of mavacamten in participants with symptomatic obstructive HCM (oHCM). Approximately 220 participants will be randomized to receive placebo or mavacamten.

Detailed Description

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Conditions

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Obstructive Hypertrophic Cardiomyopathy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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mavacamten (MYK-461)

Group Type EXPERIMENTAL

mavacamten

Intervention Type DRUG

mavacamten capsules

Placebo

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

placebo oral capsule

Interventions

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mavacamten

mavacamten capsules

Intervention Type DRUG

Placebo

placebo oral capsule

Intervention Type DRUG

Other Intervention Names

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MYK-461

Eligibility Criteria

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Inclusion Criteria

* Age 18 and greater, body weight ≥ 45kg
* Has adequate acoustic windows to enable accurate transthoracic echocardiograms (TTEs)
* Diagnosed with oHCM consistent with current American College of Cardiology Foundation/American Heart Association and European Society of Cardiology guidelines and satisfy both criteria:
* Has documented left ventricular ejection fraction (LVEF) ≥55%
* NYHA Class II or III
* Has documented oxygen saturation at rest ≥90% at Screening
* Is able to perform an upright CPET and has a respiratory exchange ratio (RER) ≥1.0 at Screening per central reading

Exclusion Criteria

* Known infiltrative or storage disorder causing cardiac hypertrophy that mimics oHCM, such as Fabry disease, amyloidosis, or Noonan syndrome with LV hypertrophy
* History of syncope or sustained ventricular tachyarrhythmia with exercise within 6 months prior to Screening
* History of resuscitated sudden cardiac arrest (at any time) or known history of appropriate implantable cardioverter defibrillator (ICD) discharge for life-threatening ventricular arrhythmia within 6 months prior to Screening
* Paroxysmal, intermittent atrial fibrillation with atrial fibrillation present at Screening
* Persistent or permanent atrial fibrillation not on anticoagulation for at least 4 weeks prior to Screening and/or not adequately rate controlled within 6 months prior to Screening
* Treatment (within 14 days prior to Screening) or planned treatment during the study with disopyramide or ranolazine
* Treatment (within 14 days prior to Screening) or planned treatment during the study with a combination of β-blockers and calcium channel blockers
* LVOT gradient with Valsalva maneuver \<30 mmHg at Screening
* Has been successfully treated with invasive septal reduction (surgical myectomy or percutaneous alcohol septal ablation \[ASA\]) within 6 months prior to Screening or plans to have either of these treatments during the study
* ICD placement within 2 months prior to Screening or planned ICD placement during the study
* Has a history or evidence of any other clinically significant disorder, condition, or disease that, in the opinion of the investigator, would pose a risk to participant safety or interfere with the study evaluation, procedures, or completion
* Prior treatment with cardiotoxic agents such as doxorubicin or similar
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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MyoKardia, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Information Team

Role: STUDY_DIRECTOR

MyoKardia, Inc.

Locations

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Mayo Clinic Arizona

Scottsdale, Arizona, United States

Site Status

Cedars-Sinai Medical Center (Smidt Heart Institute)

Los Angeles, California, United States

Site Status

UCSF School of Medicine

San Francisco, California, United States

Site Status

Stanford University

Stanford, California, United States

Site Status

Yale New Haven Hospital

New Haven, Connecticut, United States

Site Status

Mayo Clinic Jacksonville - PPDS

Jacksonville, Florida, United States

Site Status

Northwestern University

Chicago, Illinois, United States

Site Status

University Of Iowa Hospitals And Clinics

Iowa City, Iowa, United States

Site Status

Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status

University of Michigan

Ann Arbor, Michigan, United States

Site Status

Spectrum Health

Grand Rapids, Michigan, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

NYU Langone Medical Center

New York, New York, United States

Site Status

Columbia University Medical Center

New York, New York, United States

Site Status

Carolinas Medical Center

Charlotte, North Carolina, United States

Site Status

Duke Cardiology at Southpoint

Durham, North Carolina, United States

Site Status

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Site Status

Oregon Health & Science University

Portland, Oregon, United States

Site Status

St. Luke's Cardiology Associates

Bethlehem, Pennsylvania, United States

Site Status

University of Pennsylvania (Penn Heart and Vascular Center)

Philadelphia, Pennsylvania, United States

Site Status

University of Pittsburgh Medical Center Presbyterian

Pittsburgh, Pennsylvania, United States

Site Status

Methodist University Hospital

Memphis, Tennessee, United States

Site Status

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Site Status

Houston Methodist Hospital

Houston, Texas, United States

Site Status

University of Texas Houston Medical School

Houston, Texas, United States

Site Status

Intermountain Medical Center

Salt Lake City, Utah, United States

Site Status

University of Utah

Salt Lake City, Utah, United States

Site Status

University of Virginia Health System

Charlottesville, Virginia, United States

Site Status

University of Washington Medical Center

Seattle, Washington, United States

Site Status

UZ Antwerpen

Edegem, Antwerpen, Belgium

Site Status

Onze-Lieve-Vrouwziekenhuis

Aalst, Oost-Vlaanderen, Belgium

Site Status

Hôpital Erasme

Brussels, , Belgium

Site Status

Vseobecna fakultni nemocnice v Praze

Prague, , Czechia

Site Status

Institut Klinicke a Experimentalni Mediciny

Prague, , Czechia

Site Status

Aarhus Universitetshospital

Aarhus N, , Denmark

Site Status

Bispebjerg Hospital

København NV, , Denmark

Site Status

Odense Universitetshospital

Odense, , Denmark

Site Status

CHRU Nantes

Nantes, Loire-Atlantique, France

Site Status

Groupe Hospitalier Pitié Salpétrière

Paris, , France

Site Status

Hôpital Européen Georges Pompidou

Paris, , France

Site Status

Hôpital de Rangueil

Toulouse, , France

Site Status

University Medicine Göttingen

Göttingen, Neidersachsen, Germany

Site Status

Kerckhoff-Klinik-Forschungs-GmbH

Bad Nauheim, , Germany

Site Status

Charité Campus Buch - Experimental and Clinical Research Center

Berlin, , Germany

Site Status

Charité - Universitätsmedizin Berlin

Berlin, , Germany

Site Status

Cardiologicum Dresden und Pirna

Dresden, , Germany

Site Status

University Clinic Heidelberg - PPDS

Heidelberg, , Germany

Site Status

Universitatsklinikum Schleswig-Holstein

Kiel, , Germany

Site Status

Tel Aviv Sourasky Medical Center

Tel Aviv, Tel Aviv, Israel

Site Status

Barzilai Medical Center

Ashkelon, , Israel

Site Status

Hadassah Medical Center PPDS -

Jerusalem, , Israel

Site Status

Rabin Medical Center - PPDS

Petah Tikva, , Israel

Site Status

The Chaim Sheba Medical Center - The Edmond and Lily Safra Children's Hospital

Ramat Gan, , Israel

Site Status

Kaplan Medical Center

Rehovot, , Israel

Site Status

ZIV Medical Center

Safed, , Israel

Site Status

Azienda Ospedaliera Universitaria Careggi

Florence, , Italy

Site Status

Maastricht University Medical Center

Maastricht, Limburg, Netherlands

Site Status

Erasmus MC

Rotterdam, South Holland, Netherlands

Site Status

Collegium Medicum Uniwersytetu Jagiellonskiego

Krakow, Lesser Poland Voivodeship, Poland

Site Status

Kardio Klinika Brynów

Katowice, Silesian Voivodeship, Poland

Site Status

Szpital Kliniczny Przemienienia Panskiego Uniwesytetu Medycznego im. Karola Marcinkowskiego

Poznan, , Poland

Site Status

Instytut Kardiologii im Prymasa Tysiaclecia Kardynala Stefana Wyszynskiego

Warsaw, , Poland

Site Status

Hospital Garcia de Orta

Almada, , Portugal

Site Status

Hospital da Luz

Lisbon, , Portugal

Site Status

Hospital Universitario Virgen de La Arrixaca

El Palmar, Murcia, Spain

Site Status

Hospital Universitario A Coruña

A Coruña, , Spain

Site Status

Hospital Universitario Puerta de Hierro - Majadahonda

Madrid, , Spain

Site Status

Hospital Universitario Ramon y Cajal

Madrid, , Spain

Site Status

Hospital Universitario Virgen Macarena

Seville, , Spain

Site Status

University Hospital of Wales

Cardiff, South Glamergon, United Kingdom

Site Status

St Bartholomew's Hospital

London, , United Kingdom

Site Status

Countries

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United States Belgium Czechia Denmark France Germany Israel Italy Netherlands Poland Portugal Spain United Kingdom

References

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Wang A, Lakdawala NK, Abraham TP, Nilles EK, Wojdyla DM, Owens AT, Bach RG, Saberi S, Sehnert A, Cresci S. Association Between age or Duration of Diagnosis in Obstructive Hypertrophic Cardiomyopathy and Response to Mavacamten Treatment: Exploratory Analysis of the EXPLORER-HCM Trial. J Card Fail. 2025 Jun;31(6):901-911. doi: 10.1016/j.cardfail.2024.10.449. Epub 2024 Dec 7.

Reference Type DERIVED
PMID: 39653325 (View on PubMed)

Arnold SV, Gosch KL, Dolan C, Fine JT, Masri A, Saberi S, Wang A, Elliott PM, Hegde SM, Lam J, Sehnert AJ, Cresci S, Bach RG, Spertus JA. Association of Echocardiographic Parameters and Health Status in Patients With Obstructive Hypertrophic Cardiomyopathy: Insights From EXPLORER-HCM. Circulation. 2024 Nov 5;150(19):1560-1562. doi: 10.1161/CIRCULATIONAHA.123.067470. Epub 2024 Nov 4. No abstract available.

Reference Type DERIVED
PMID: 39495835 (View on PubMed)

Garcia-Pavia P, Oreziak A, Masri A, Barriales-Villa R, Abraham TP, Owens AT, Jensen MK, Wojakowski W, Seidler T, Hagege A, Lakdawala NK, Wang A, Wheeler MT, Choudhury L, Balaratnam G, Shah A, Fox S, Hegde SM, Olivotto I. Long-term effect of mavacamten in obstructive hypertrophic cardiomyopathy. Eur Heart J. 2024 Dec 16;45(47):5071-5083. doi: 10.1093/eurheartj/ehae579.

Reference Type DERIVED
PMID: 39217450 (View on PubMed)

Cresci S, Bach RG, Saberi S, Owens AT, Spertus JA, Hegde SM, Lakdawala NK, Nilles EK, Wojdyla DM, Sehnert AJ, Wang A. Effect of Mavacamten in Women Compared With Men With Obstructive Hypertrophic Cardiomyopathy: Insights From EXPLORER-HCM. Circulation. 2024 Feb 13;149(7):498-509. doi: 10.1161/CIRCULATIONAHA.123.065600. Epub 2023 Nov 14.

Reference Type DERIVED
PMID: 37961906 (View on PubMed)

Wang A, Spertus JA, Wojdyla DM, Abraham TP, Nilles EK, Owens AT, Saberi S, Cresci S, Sehnert A, Lakdawala NK. Mavacamten for Obstructive Hypertrophic Cardiomyopathy With or Without Hypertension: Post-Hoc Analysis of the EXPLORER-HCM Trial. JACC Heart Fail. 2024 Mar;12(3):567-579. doi: 10.1016/j.jchf.2023.07.030. Epub 2023 Oct 18.

Reference Type DERIVED
PMID: 37855754 (View on PubMed)

Wheeler MT, Olivotto I, Elliott PM, Saberi S, Owens AT, Maurer MS, Masri A, Sehnert AJ, Edelberg JM, Chen YM, Florea V, Malhotra R, Wang A, Oreziak A, Myers J. Effects of Mavacamten on Measures of Cardiopulmonary Exercise Testing Beyond Peak Oxygen Consumption: A Secondary Analysis of the EXPLORER-HCM Randomized Trial. JAMA Cardiol. 2023 Mar 1;8(3):240-247. doi: 10.1001/jamacardio.2022.5099.

Reference Type DERIVED
PMID: 36652223 (View on PubMed)

Nassif M, Fine JT, Dolan C, Reaney M, Addepalli P, Allen VD, Sehnert AJ, Gosch K, Spertus JA. Validation of the Kansas City Cardiomyopathy Questionnaire in Symptomatic Obstructive Hypertrophic Cardiomyopathy. JACC Heart Fail. 2022 Aug;10(8):531-539. doi: 10.1016/j.jchf.2022.03.002. Epub 2022 May 4.

Reference Type DERIVED
PMID: 35902155 (View on PubMed)

Reaney M, Addepalli P, Allen V, Spertus JA, Dolan C, Sehnert AJ, Fine JT. Longitudinal Psychometric Analysis of the Hypertrophic Cardiomyopathy Symptom Questionnaire (HCMSQ) Using Outcomes from the Phase III EXPLORER-HCM Trial. Pharmacoecon Open. 2022 Jul;6(4):575-586. doi: 10.1007/s41669-022-00340-8. Epub 2022 Jun 20.

Reference Type DERIVED
PMID: 35718845 (View on PubMed)

Hegde SM, Lester SJ, Solomon SD, Michels M, Elliott PM, Nagueh SF, Choudhury L, Zemanek D, Zwas DR, Jacoby D, Wang A, Ho CY, Li W, Sehnert AJ, Olivotto I, Abraham TP. Effect of Mavacamten on Echocardiographic Features in Symptomatic Patients With Obstructive Hypertrophic Cardiomyopathy. J Am Coll Cardiol. 2021 Dec 21;78(25):2518-2532. doi: 10.1016/j.jacc.2021.09.1381.

Reference Type DERIVED
PMID: 34915982 (View on PubMed)

Xie J, Wang Y, Xu Y, Fine JT, Lam J, Garrison LP. Assessing health-related quality-of-life in patients with symptomatic obstructive hypertrophic cardiomyopathy: EQ-5D-based utilities in the EXPLORER-HCM trial. J Med Econ. 2022 Jan-Dec;25(1):51-58. doi: 10.1080/13696998.2021.2011301.

Reference Type DERIVED
PMID: 34907813 (View on PubMed)

Burstein Waldman C, Owens A. A plain language summary of the EXPLORER-HCM study: mavacamten for obstructive hypertrophic cardiomyopathy. Future Cardiol. 2021 Oct;17(7):1269-1275. doi: 10.2217/fca-2021-0044. Epub 2021 May 21.

Reference Type DERIVED
PMID: 34018809 (View on PubMed)

Spertus JA, Fine JT, Elliott P, Ho CY, Olivotto I, Saberi S, Li W, Dolan C, Reaney M, Sehnert AJ, Jacoby D. Mavacamten for treatment of symptomatic obstructive hypertrophic cardiomyopathy (EXPLORER-HCM): health status analysis of a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2021 Jun 26;397(10293):2467-2475. doi: 10.1016/S0140-6736(21)00763-7. Epub 2021 May 15.

Reference Type DERIVED
PMID: 34004177 (View on PubMed)

Olivotto I, Oreziak A, Barriales-Villa R, Abraham TP, Masri A, Garcia-Pavia P, Saberi S, Lakdawala NK, Wheeler MT, Owens A, Kubanek M, Wojakowski W, Jensen MK, Gimeno-Blanes J, Afshar K, Myers J, Hegde SM, Solomon SD, Sehnert AJ, Zhang D, Li W, Bhattacharya M, Edelberg JM, Waldman CB, Lester SJ, Wang A, Ho CY, Jacoby D; EXPLORER-HCM study investigators. Mavacamten for treatment of symptomatic obstructive hypertrophic cardiomyopathy (EXPLORER-HCM): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2020 Sep 12;396(10253):759-769. doi: 10.1016/S0140-6736(20)31792-X. Epub 2020 Aug 29.

Reference Type DERIVED
PMID: 32871100 (View on PubMed)

Ho CY, Olivotto I, Jacoby D, Lester SJ, Roe M, Wang A, Waldman CB, Zhang D, Sehnert AJ, Heitner SB. Study Design and Rationale of EXPLORER-HCM: Evaluation of Mavacamten in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy. Circ Heart Fail. 2020 Jun;13(6):e006853. doi: 10.1161/CIRCHEARTFAILURE.120.006853. Epub 2020 Jun 5.

Reference Type DERIVED
PMID: 32498620 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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MYK-461-005

Identifier Type: -

Identifier Source: org_study_id

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