Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic nHCM (ACACIA-HCM)

• ClinicalTrials.gov Identifier: NCT06081894
• Recruitment Status: Recruiting
• First Posted: October 13, 2023
• Last Update Posted: April 29, 2024
• Sponsor: Cytokinetics
• Information provided by (Responsible Party): Cytokinetics

Tracking Information

• First Submitted Date: August 31, 2023
• First Posted Date: October 13, 2023
• Last Update Posted Date: April 29, 2024
• Actual Study Start Date: August 30, 2023
• Estimated Primary Completion Date: June 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 12, 2023)

Change in Kansas City Cardiomyopathy Questionnaire - Clinical Summary Score (KCCQ-CSS) [ Time Frame: Baseline to Week 36 ]

Effect of aficamten compared with placebo on participant health status

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 12, 2023)

• Change in composite of two Z-scores of CPET parameters (pVO2 and VE/VCO2 slope) [ Time Frame: 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 [ Time Frame: Baseline to Week 36 ]
  Effect of aficamten compared with placebo on NYHA Functional Classification
• Change in NT-proBNP [ Time Frame: Baseline to Week 36 ]
  Effect of aficamten compared with placebo on a biomarker of cardiac wall stress
• Change in LAVI [ Time Frame: 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) [ Time Frame: Baseline to End of Study, Week 72 ]
  Effect of aficamten compared with placebo on cardiovascular events

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic nHCM
• Official Title: A Phase 3, Multi-Center, Randomized, Double-Blind Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic Non-Obstructive Hypertrophic Cardiomyopathy
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Symptomatic Non-Obstructive Hypertrophic Cardiomyopathy

Intervention

• Drug: Aficamten
  Oral Tablet
• Drug: Placebo
  Oral Tablet

Study Arms

• Experimental: 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.
  Intervention: Drug: Aficamten
• Placebo Comparator: Placebo
  Participants in this arm will receive placebo, for up to 72 weeks.
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 12, 2023): 420
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: September 2026
• Estimated Primary Completion Date: June 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 85 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Cytokinetics MD; 650-624-2929; medicalaffairs@cytokinetics.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT06081894
• Other Study ID Numbers: CY 6033; 2023-505797-15-00 ( Other Identifier: EU CTR Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Cytokinetics
• Original Responsible Party: Same as current
• Current Study Sponsor: Cytokinetics
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Cytokinetics MD; Cytokinetics

• PRS Account: Cytokinetics
• Verification Date: December 2023