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

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ClinicalTrials.gov Identifier: NCT06081894
Recruitment Status : Recruiting
First Posted : October 13, 2023
Last Update Posted : May 20, 2024
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Symptomatic Non-Obstructive Hypertrophic Cardiomyopathy Drug: Aficamten Drug: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 420 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : August 30, 2023
Estimated Primary Completion Date : June 2026
Estimated Study Completion Date : September 2026

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cardiomyopathy

Arm Intervention/treatment
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.
Drug: Aficamten
Oral Tablet

Placebo Comparator: Placebo
Participants in this arm will receive placebo, for up to 72 weeks.
Drug: Placebo
Oral Tablet




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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

  2. 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

  3. Change in NT-proBNP [ Time Frame: Baseline to Week 36 ]
    Effect of aficamten compared with placebo on a biomarker of cardiac wall stress

  4. Change in LAVI [ Time Frame: Baseline to Week 36 ]
    Effect of aficamten compared with placebo on echocardiographic measures of structural remodeling

  5. 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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT06081894


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

Locations
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Sponsors and Collaborators
Cytokinetics
Investigators
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Study Director: Cytokinetics MD Cytokinetics
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Responsible Party: Cytokinetics
ClinicalTrials.gov Identifier: NCT06081894    
Other Study ID Numbers: CY 6033
2023-505797-15-00 ( Other Identifier: EU CTR Number )
First Posted: October 13, 2023    Key Record Dates
Last Update Posted: May 20, 2024
Last Verified: December 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Cytokinetics:
CK-3773274
CK-274
Aficamten
Symptomatic Non-Obstructive Hypertrophic Cardiomyopathy
nHCM
ACACIA-HCM
ACACIA
Additional relevant MeSH terms:
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Cardiomyopathies
Cardiomyopathy, Hypertrophic
Hypertrophy
Heart Diseases
Cardiovascular Diseases
Pathological Conditions, Anatomical
Aortic Stenosis, Subvalvular
Aortic Valve Stenosis
Aortic Valve Disease
Heart Valve Diseases