Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic nHCM

Phase 3

Recruiting

• Conditions: Symptomatic Non-Obstructive Hypertrophic Cardiomyopathy
• Interventions: Drug: Placebo; Drug: Aficamten

• Registration Number: NCT06081894
• Lead Sponsor: Cytokinetics

Brief Summary

This clinical trial will study the effects of aficamten (versus placebo) on the quality of life, exercise capacity, and clinical outcomes of patients with non-obstructive hypertrophic cardiomyopathy.

Detailed Description

Not available

Study Timeline

• Study Start: 2023-08-30
• Study First Submitted: 2023-08-31
• Study First Submitted QC: 2023-10-12
• Study First Posted: 2023-10-13
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-03
• Last Update Posted: 2024-12-04
• Primary Completion: 2026-06
• Study Completion: 2026-09

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 420

Inclusion Criteria

• Between 18-85 years of age

• Body mass index < 40 kg/m2

• Diagnosed with nHCM and has a screening echocardiogram with the following:

  • End-diastolic left ventricular (LV) wall thickness:

    • ≥ 15 mm in one or more myocardial segments OR
    • ≥ 13 mm in one or more wall segments and a known disease-causing gene mutation or positive family history of HCM AND
    • Resting LVOT-G < 30 mmHg AND Valsalva LVOT-G < 50 mmHg AND
    • LVEF ≥ 60%

  • Participants with a history of intracavitary obstruction are eligible.

• NYHA class II or III

• Respiratory exchange ratio of ≥ 1.00 at screening by cardiopulmonary exercise testing (CPET) and predicted peak oxygen uptake (pVO2) ≤ 90% for age and sex

• KCCQ-CSS score of ≥ 30 and ≤ 85

• NT-proBNP of:

  • NT-pro BNP ≥ 300 pg/mL or NT-proBNP ≥ 900 pg/mL if in atrial fibrillation or atrial flutter OR
  • For Black participants, an NT-pro BNP ≥ 225 pg/mL or NT-proBNP ≥ 675 pg/mL if in atrial fibrillation or atrial flutter

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Exclusion Criteria

• Significant valvular heart disease (per Investigator judgment)

  • Moderate or severe valvular aortic stenosis or fixed subaortic obstruction
  • Moderate or severe mitral regurgitation

• Known or suspected infiltrative, genetic or storage disorder causing cardiac hypertrophy that mimics nHCM (eg, Noonan syndrome, Fabry disease, amyloidosis)

• Known current unrevascularized coronary artery stenosis of ≥ 70% or documented history of myocardial infarction.

• History of LV systolic dysfunction (LVEF < 45%) or stress cardiomyopathy

• Inability to exercise on a treadmill or bicycle (eg, orthopedic limitations)

• Documented room air oxygen saturation reading < 90% at screening or history of significant chronic obstructive pulmonary disease or severe/significant pulmonary hypertension

• History of syncope, symptomatic ventricular arrhythmia, or sustained ventricular tachyarrhythmia with exercise within 3 months prior to screening

• History of resistant hypertension (persistently elevated blood pressure despite maximal doses of 3 or more classes of medications for hypertension control)

• Screening diastolic blood pressure ≥ 100 mmHg

• Received prior treatment with aficamten

• Received treatment with mavacamten within 3 months prior to screening (must be discussed with the medical monitor prior to screening)

• Undergone septal reduction therapy < 6 months prior to screening

• Is being considered for or is likely to be considered for heart transplant listing or left ventricular assist device placement during the study period

• Paroxysmal or permanent atrial fibrillation is excluded only if:

  • rhythm restoring treatment (e.g., direct-current cardioversion, atrial fibrillation ablation procedure, or antiarrhythmic therapy) has been required ≤ 3 months prior to screening
  • rate control and anticoagulation have not been achieved for at least 3 months prior to screening.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Participants in this arm will receive placebo, for up to 72 weeks.
Aficamten	Aficamten	Participants in this arm will receive a single daily oral dose of 5 mg, 10 mg, 15 mg, or 20 mg of aficamten with dose levels guided by echocardiography assessments, for up to 72 weeks.

Primary Outcome Measures

Name	Time	Method
Change in Kansas City Cardiomyopathy Questionnaire - Clinical Summary Score (KCCQ-CSS)	Baseline to Week 36	Effect of aficamten compared with placebo on participant health status

Secondary Outcome Measures

Name	Time	Method
Change in composite of two Z-scores of CPET parameters (pVO2 and VE/VCO2 slope)	Baseline to Week 36	Effect of aficamten compared with placebo on global exercise capacity based on maximal and sub-maximal exercise performance
Proportion of participants with ≥ 1 class improvement in NYHA Functional Class	Baseline to Week 36	Effect of aficamten compared with placebo on NYHA Functional Classification
Change in NT-proBNP	Baseline to Week 36	Effect of aficamten compared with placebo on a biomarker of cardiac wall stress
Change in LAVI	Baseline to Week 36	Effect of aficamten compared with placebo on echocardiographic measures of structural remodeling
Time to first CV event (CV death; heart transplantation or left ventricular assist device; aborted sudden cardiac death; non-fatal stroke; heart failure hospitalization; or cardiac arrhythmia requiring treatment or hospitalization)	Baseline to End of Study, Week 72	Effect of aficamten compared with placebo on cardiovascular events

Trial Locations

Locations (84)

Virginia Mason Medical Center; 🇺🇸 Seattle, Washington, United States

Medical College of Wisconsin/Froedtert Hospital; 🇺🇸 Milwaukee, Wisconsin, United States

Fundacao Felice Rocho / Hospital Felicio Rocho; 🇧🇷 Minas Gerais, Brazil

Hospital das Clinicas de Faculdade de Medicina de Ribeirao Preto da Universidade de Sao Paulo - HCFMRP; 🇧🇷 São Paulo, Brazil

People's Hospital of Liaoning Province; 🇨🇳 Shenyang, China

The Barzilai University Medical Center 2 - Cardiology Division; 🇮🇱 Ashkelon, Israel

Division of Cardiology Hadassah Medical Center; 🇮🇱 Jerusalem, Israel

Ziv Medical Center; 🇮🇱 Safed, Israel

NHS Tayside Ninewells Hospital & Medical School; 🇬🇧 Dundee, Scotland, United Kingdom

NHS Greater Glasgow and Clyde Queen Elizabeth University Hospital; 🇬🇧 Glasgow, United Kingdom

Barts Health NHS Trust St Bartholomew's Hospital; 🇬🇧 London, United Kingdom

Royal Brompton Hospital; 🇬🇧 London, United Kingdom

University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States

Westchester Medical Center; 🇺🇸 Valhalla, New York, United States

WVU Medicine; 🇺🇸 Morgantown, West Virginia, United States

NUPEC Cardio / Cardio HVC; 🇧🇷 Minas Gerais, Brazil

Instituto Dante Pazzanese de Cardiologia; 🇧🇷 São Paulo, Brazil

Instituto do Coracao do Hospital de Aguiar; 🇧🇷 São Paulo, Brazil

Associacao Lar Sao Francisco de Assis na Providencia de Deus - Hospital Universitario Sao Francisco na Providencia de Deus (HUSF); 🇧🇷 São Paulo, Brazil

Saraiva & Berlinger LTDA - EPP/IPECC - Instituto de Pesquisa Clinical de Campinas; 🇧🇷 São Paulo, Brazil

Guangdong Provincial People's Hospital; 🇨🇳 Guangzhou, China

Shanghai Ruijin Hospital Luwan Branch; 🇨🇳 Shanghai, China

Remin Hospital of Wuhan University; 🇨🇳 Wuhan, China

The 1st affi. Hospital of Xi'an Jiaotong University; 🇨🇳 Xi'an, China

Assistance Publique Hopitaux de Marseille; 🇫🇷 Marseille, France

Clinique Du Millenaire; 🇫🇷 Montpellier, France

Centre Hospitalier Universitaire De Montpellier; 🇫🇷 Montpellier, France

Assistance Publique Hopitaux de Paris; 🇫🇷 Paris, France

Alaska Heart and Vascular Institute; 🇺🇸 Anchorage, Alaska, United States

UC San Diego Health - Sulpizio Cardiovascular Center; 🇺🇸 La Jolla, California, United States

Cedars-Sinai Medical Center (Smidt Heart Institute); 🇺🇸 Los Angeles, California, United States

University of California San Francisco; 🇺🇸 San Francisco, California, United States

Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center; 🇺🇸 Torrance, California, United States

Yale New Haven Hospital; 🇺🇸 New Haven, Connecticut, United States

MedStar Washington Hospital Center; 🇺🇸 Washington, District of Columbia, United States

Holy Cross Medical Group - Cardiology Associates; 🇺🇸 Fort Lauderdale, Florida, United States

Investigational Drug Services, AdventHealth Orlando; 🇺🇸 Orlando, Florida, United States

Emory Clinic; 🇺🇸 Atlanta, Georgia, United States

Piedmont Heart Institute (CPET); 🇺🇸 Fayetteville, Georgia, United States

The Queen's Medical Center-Punchbowl; 🇺🇸 Honolulu, Hawaii, United States

Northwestern University; 🇺🇸 Evanston, Illinois, United States

Ascension St. Vincent; 🇺🇸 Indianapolis, Indiana, United States

MedStar Union Memorial Hospital; 🇺🇸 Baltimore, Maryland, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Brigham and Women's Hospital; 🇺🇸 Boston, Massachusetts, United States

Lahey Hospital & Medical Center; 🇺🇸 Burlington, Massachusetts, United States

Michigan Medicine; 🇺🇸 Ann Arbor, Michigan, United States

Henry Ford Hospital; 🇺🇸 Detroit, Michigan, United States

M Health Fairview University of Minnesota Medical Center - East Bank; 🇺🇸 Minneapolis, Minnesota, United States

Saint Luke's Hospital of Kansas City; 🇺🇸 Kansas City, Missouri, United States

Arizona Cardiovascular Research Center; 🇺🇸 Las Vegas, Nevada, United States

Morristown Medical Center; 🇺🇸 Morristown, New Jersey, United States

NYU Langone Health; 🇺🇸 New York, New York, United States

Columbia University Medical Center/New York Presbyterian Hospital; 🇺🇸 New York, New York, United States

Sanger Heart & Vascular Institute - HCM Clinic; 🇺🇸 Charlotte, North Carolina, United States

The Lindner Research Center at The Christ Hospital; 🇺🇸 Cincinnati, Ohio, United States

Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States

Providence St. Vincent Medical Center; 🇺🇸 Portland, Oregon, United States

Oregon Health & Science University; 🇺🇸 Portland, Oregon, United States

Hospital of the University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States

Medical University of South Carolina; 🇺🇸 Charleston, South Carolina, United States

Greenville Memorial Hospital; 🇺🇸 Greenville, South Carolina, United States

Ascension Saint Thomas Heart West; 🇺🇸 Nashville, Tennessee, United States

Vanderbilt University Medical Center; 🇺🇸 Nashville, Tennessee, United States

Baylor College of Medicine; 🇺🇸 Houston, Texas, United States

Houston Methodist Hospital; 🇺🇸 Houston, Texas, United States

Intermountain Medical Center; 🇺🇸 Murray, Utah, United States

University of Virginia; 🇺🇸 Charlottesville, Virginia, United States

Inova Health Care Services; 🇺🇸 Falls Church, Virginia, United States

Carilion Clinic Cardiology; 🇺🇸 Roanoke, Virginia, United States

The First Hospital of Jilin University; 🇨🇳 Jilin, China

Zhongda Hospital Southeast University; 🇨🇳 Nanjin, China

Zhongshan Hospital Fudan University; 🇨🇳 Shanghai, China

University of Iowa Hospitals and Clinics; 🇺🇸 Iowa City, Iowa, United States

The University of Kansas Medical Center; 🇺🇸 Kansas City, Kansas, United States

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States

Weill Cornell Medicine; 🇺🇸 New York, New York, United States

Mount Sinai Hospital; 🇺🇸 New York, New York, United States

UPMC Presbyterian; 🇺🇸 Pittsburgh, Pennsylvania, United States

University of Utah Health; 🇺🇸 Salt Lake City, Utah, United States

Providence Sacred Heart Medical Center & Children's Hospital (CPET); 🇺🇸 Spokane, Washington, United States

University of Wisconsin Hospitals and Clinics; 🇺🇸 Madison, Wisconsin, United States

The Prince Charles Hospital; 🇦🇺 Chermside, Queensland, Australia

Flinders Medical Centre Cardiology Research; 🇦🇺 Adelaide, South Australia, Australia