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

NCT03470545 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: MYK-461-005
• Study Type: interventional
• Target: 251
• Locations: 13 countries
• Sites: 71

Brief Summary

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.

Conditions

Obstructive Hypertrophic Cardiomyopathy

Keywords

Symptomatic, left ventricular outflow tract gradient

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Achieving A Clinical Response

  A positive clinical response (value="YES") is defined as having achieved either an improvement of at least 1.5 mL/kg/min in peak oxygen consumption (pVO2) as determined by cardiopulmonary exercise testing (CPET) and a reduction of one or more class in New York Heart Association (NYHA) functional classification (e.g.I, II, III, or IV) -OR- an improvement of 3.0 mL/kg/min or more in pVO2 with no worsening in NYHA Functional Class.

  30 weeks

Secondary Outcomes (5)

• Changes From Baseline to Week 30 in Post Exercise in LVOT Peak Gradient.

  30 weeks

• Change From Baseline to Week 30 in pVO2 as Assessed by CPET

  30 weeks

• Proportion of Participants With at Least 1 Class Improvement in NYHA Functional Class From Baseline to Week 30

  30 weeks

• Change From Baseline to Week 30 in Participant-reported Health-related Quality of Life as Assessed by the KCCQ Score

  30 weeks

• Change From Baseline to Week 30 in Participant-reported Severity of HCM Symptoms as Assessed by the HCMSQ Score

  30 weeks

Study Arms (2)

mavacamten (MYK-461)

EXPERIMENTAL

Drug: mavacamten

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

mavacamten DRUG

mavacamten capsules

Also known as: MYK-461

mavacamten (MYK-461)

Placebo DRUG

placebo oral capsule

Placebo

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• MyoKardia, Inc.: lead

Study Sites (71)

Mayo Clinic Arizona

Scottsdale, Arizona, 85259, United States

Location

Cedars-Sinai Medical Center (Smidt Heart Institute)

Los Angeles, California, 90048, United States

Location

UCSF School of Medicine

San Francisco, California, 94143, United States

Location

Stanford University

Stanford, California, 94305, United States

Location

Yale New Haven Hospital

New Haven, Connecticut, 16511, United States

Location

Mayo Clinic Jacksonville - PPDS

Jacksonville, Florida, 32224, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University Of Iowa Hospitals And Clinics

Iowa City, Iowa, 52242, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Spectrum Health

Grand Rapids, Michigan, 49512, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

NYU Langone Medical Center

New York, New York, 10017, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Carolinas Medical Center

Charlotte, North Carolina, 28203, United States

Location

Duke Cardiology at Southpoint

Durham, North Carolina, 27710, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

St. Luke's Cardiology Associates

Bethlehem, Pennsylvania, 18018, United States

Location

University of Pennsylvania (Penn Heart and Vascular Center)

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh Medical Center Presbyterian

Pittsburgh, Pennsylvania, 15213, United States

Location

Methodist University Hospital

Memphis, Tennessee, 38163, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75235, United States

Location

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

University of Texas Houston Medical School

Houston, Texas, 77030, United States

Location

Intermountain Medical Center

Salt Lake City, Utah, 84107, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

University of Virginia Health System

Charlottesville, Virginia, 22903, United States

Location

University of Washington Medical Center

Seattle, Washington, 98195, United States

Location

UZ Antwerpen

Edegem, Antwerpen, 2650, Belgium

Location

Onze-Lieve-Vrouwziekenhuis

Aalst, Oost-Vlaanderen, 9300, Belgium

Location

Hôpital Erasme

Brussels, 1070, Belgium

Location

Vseobecna fakultni nemocnice v Praze

Prague, 128 08, Czechia

Location

Institut Klinicke a Experimentalni Mediciny

Prague, Czechia

Location

Aarhus Universitetshospital

Aarhus N, 8200, Denmark

Location

Bispebjerg Hospital

København NV, 2400, Denmark

Location

Odense Universitetshospital

Odense, 5000, Denmark

Location

CHRU Nantes

Nantes, Loire-Atlantique, 44805, France

Location

Groupe Hospitalier Pitié Salpétrière

Paris, 75013, France

Location

Hôpital Européen Georges Pompidou

Paris, 75015, France

Location

Hôpital de Rangueil

Toulouse, 31403, France

Location

University Medicine Göttingen

Göttingen, Neidersachsen, Germany

Location

Kerckhoff-Klinik-Forschungs-GmbH

Bad Nauheim, 61231, Germany

Location

Charité Campus Buch - Experimental and Clinical Research Center

Berlin, 13125, Germany

Location

Charité - Universitätsmedizin Berlin

Berlin, 13353, Germany

Location

Cardiologicum Dresden und Pirna

Dresden, 01277, Germany

Location

University Clinic Heidelberg - PPDS

Heidelberg, 69120, Germany

Location

Universitatsklinikum Schleswig-Holstein

Kiel, 24105, Germany

Location

Tel Aviv Sourasky Medical Center

Tel Aviv, Tel Aviv, 62431, Israel

Location

Barzilai Medical Center

Ashkelon, 78278, Israel

Location

Hadassah Medical Center PPDS -

Jerusalem, 91120, Israel

Location

Rabin Medical Center - PPDS

Petah Tikva, 49100, Israel

Location

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

Ramat Gan, 52621, Israel

Location

Kaplan Medical Center

Rehovot, 76100, Israel

Location

ZIV Medical Center

Safed, 13100, Israel

Location

Azienda Ospedaliera Universitaria Careggi

Florence, Italy

Location

Maastricht University Medical Center

Maastricht, Limburg, 6229 HX, Netherlands

Location

Erasmus MC

Rotterdam, South Holland, 3015GD, Netherlands

Location

Collegium Medicum Uniwersytetu Jagiellonskiego

Krakow, Lesser Poland Voivodeship, 31-501, Poland

Location

Kardio Klinika Brynów

Katowice, Silesian Voivodeship, Poland

Location

Szpital Kliniczny Przemienienia Panskiego Uniwesytetu Medycznego im. Karola Marcinkowskiego

Poznan, 61-848, Poland

Location

Instytut Kardiologii im Prymasa Tysiaclecia Kardynala Stefana Wyszynskiego

Warsaw, 04-628, Poland

Location

Hospital Garcia de Orta

Almada, 2805-267, Portugal

Location

Hospital da Luz

Lisbon, 1500-650, Portugal

Location

Hospital Universitario Virgen de La Arrixaca

El Palmar, Murcia, 30120, Spain

Location

Hospital Universitario A Coruña

A Coruña, Spain

Location

Hospital Universitario Puerta de Hierro - Majadahonda

Madrid, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, Spain

Location

Hospital Universitario Virgen Macarena

Seville, 41009, Spain

Location

University Hospital of Wales

Cardiff, South Glamergon, CF14 4XW, United Kingdom

Location

St Bartholomew's Hospital

London, W1G 8PH, United Kingdom

Location

Related Publications (14)

• 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.

  PMID: 39653325 DERIVED

• 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.

  PMID: 39495835 DERIVED

• 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.

  PMID: 39217450 DERIVED

• 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.

  PMID: 37961906 DERIVED

• 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.

  PMID: 37855754 DERIVED

• 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.

  PMID: 36652223 DERIVED

• 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.

  PMID: 35902155 DERIVED

• 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.

  PMID: 35718845 DERIVED

• 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.

  PMID: 34915982 DERIVED

• 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.

  PMID: 34907813 DERIVED

• 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.

  PMID: 34018809 DERIVED

• 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.

  PMID: 34004177 DERIVED

• 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.

  PMID: 32871100 DERIVED

• 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.

  PMID: 32498620 DERIVED

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

• Medical Information Team

  MyoKardia, Inc.

  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

Study Record Dates

• First Submitted: March 12, 2018
• First Posted: March 20, 2018
• Study Start: May 29, 2018
• Primary Completion: March 14, 2020
• Study Completion: May 6, 2020
• Last Updated: October 4, 2021
• Results First Posted: October 4, 2021

Record last verified: 2020-05

Locations

DE (7); US (29); BE (3); IT (1); PL (4); DK (3); ES (5); IL (7); GB (2); CZ (2); NL (2); PT (2); FR (4)