Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic nHCM
- Conditions
- Symptomatic Non-Obstructive Hypertrophic Cardiomyopathy
- Interventions
- Drug: Placebo
- 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
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 500
-
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 ≤ 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
-
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)
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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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 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. Placebo Placebo Participants in this arm will receive placebo, 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
Change in pVO2 Baseline to Week 36 Effect of aficamten compared with placebo on maximal exercise capacity
- Secondary Outcome Measures
Name Time Method Time to first CV event Baseline to End of Study, Week 72 Effect of aficamten compared with placebo on cardiovascular events (ie, CV death, heart transplantation or left ventricular assist device, aborted sudden cardiac death, non-fatal stroke, heart failure hospitalization, or cardiac arrhythmia (atrial fibrillation or ventricular tachyarrhythmia) requiring treatment or hospitalization)
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
Trial Locations
- Locations (180)
Keck Medical Center of USC (Outpatient Clinic)
🇺🇸Los Angeles, California, United States
UCLA Medical Center Cardiovascular Clinic
🇺🇸Los Angeles, California, United States
Northwell Health North Shore University Hospital
🇺🇸Manhasset, New York, United States
University Hospitals Cleveland Medical Center
🇺🇸Cleveland, Ohio, United States
VCU Health Downtown Medical Campus
🇺🇸Richmond, Virginia, United States
Aurora St. Luke's Medical Center
🇺🇸Milwaukee, Wisconsin, United States
ICBA - Instituto Cardiovascular de Buenos Aires
🇦🇷Buenos Aires, Argentina
Hospital Privado Centro Medico de Cordoba S.A
🇦🇷Córdoba, Argentina
CLINICOR Clinica Cardiologica LTDA
🇧🇷Ribeirão Preto, Brazil
Royal Alexandra Hospital
🇨🇦Edmonton, Alberta, Canada
Scroll for more (170 remaining)Keck Medical Center of USC (Outpatient Clinic)🇺🇸Los Angeles, California, United States