Dose-finding Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of CK-3773274 in Adults With Hypertrophic Cardiomyopathy

NCT04219826 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: CY 60212019-002785-12
• Study Type: interventional
• Target: 96
• Locations: 4 countries
• Sites: 22

Brief Summary

This study is being performed to understand the effect of different doses of CK-3773274 on patients with hypertrophic cardiomyopathy (HCM).

Conditions

Hypertrophic Cardiomyopathy (HCM)

Keywords

CK-3773274; CK-274; obstructive hypertrophic cardiomyopathy; oHCM; REDWOOD-HCM; non-obstructive hypertrophic cardiomyopathy; nHCM; hypertrophic cardiomyopathy; HCM; aficamten; CY 6021

Outcome Measures

Primary Outcomes (3)

• Incidence of Adverse Events (AEs)

  Participant incidence of reported AEs to determine the safety and tolerability of aficamten in participants with HCM.

  14 weeks

• Incidence of Left Ventricular Ejection Fraction (LVEF) < 50%

  Participant incidence of LVEF \< 50% as assessed by the core laboratory assessment.

  14 weeks

• Incidence of Serious Adverse Events (SAEs)

  Participant incidence of reported SAEs to determine the safety and tolerability of aficamten in participants with symptomatic HCM.

  14 weeks

Secondary Outcomes (5)

• Slope of the Relationship of the Plasma Concentration of CK-3773274 to the Change From Baseline in the Resting Left Ventricular Outflow Track Gradient (LVOT-G)

  Baseline and 10 weeks

• Slope of the Relationship of the Plasma Concentration of CK-3773274 to the Change From Baseline in the Post-Valsalva LVOT-G

  Baseline and 10 Weeks

• Change From Baseline in Resting LVOT-G Over Time as a Function of Dose.

  Baseline and 10 Weeks

• Change From Baseline in Post-Valsalva LVOT-G Over Time as a Function of Dose.

  10 weeks

• Slope of the Relationship of the Plasma Concentration of CK-3773274 to the Change From Baseline in the Resting LVEF

  Day 1 to End of Study (EOS) (Week 14)

Study Arms (6)

Cohort 1 (oHCM) - Aficamten

EXPERIMENTAL

Participants received CK-3773274 doses of 5 - 15 mg once daily with dose levels guided by echocardiography assessments for up to 10 weeks

Drug: CK-3773274 (5 - 15 mg)

Cohort 1 (oHCM) - Placebo

PLACEBO COMPARATOR

Participants received placebo once daily for up to 10 weeks

Drug: Placebo for CK-3773274

Cohort 2 (oHCM) - Aficamten

EXPERIMENTAL

Participants received CK-3773274 doses 10 - 30 mg once daily with dose levels guided by echocardiography assessments for up to 10 weeks

Drug: CK-3773274 (10 - 30 mg)

Cohort 2 (oHCM) - Placebo

PLACEBO COMPARATOR

Participants received placebo once daily for up to 10 weeks

Drug: Placebo for CK-3773274

Cohort 3 (oHCM) - Aficamten & Background Disopyramide

EXPERIMENTAL

Participants received CK-3773274 doses 5 - 15 mg once daily with dose levels guided by echocardiography assessments for up to 10 weeks while taking disopyramide

Drug: CK-3773274 (5 - 15 mg)

Cohort 4 (nHCM) - Aficamten

EXPERIMENTAL

Participants received CK-3773274 doses of 5 - 15 mg once daily with dose levels guided by echocardiography assessments for up to 10 weeks

Drug: CK-3773274 (5 - 15 mg)

Interventions

CK-3773274 (5 - 15 mg) DRUG

CK-3773274 tablets administered orally once daily

Cohort 1 (oHCM) - Aficamten; Cohort 3 (oHCM) - Aficamten & Background Disopyramide; Cohort 4 (nHCM) - Aficamten

CK-3773274 (10 - 30 mg) DRUG

CK-3773274 tablets administered orally once daily

Cohort 2 (oHCM) - Aficamten

Placebo for CK-3773274 DRUG

Placebo administered orally once daily

Cohort 1 (oHCM) - Placebo; Cohort 2 (oHCM) - Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females between 18 and 85 years of age at screening.
• Body weight is ≥45 kg at screening.
• Diagnosed with HCM per the following criteria:
• Has left ventricular (LV) hypertrophy with non-dilated LV chamber in the absence of other cardiac disease.
• Has minimal wall thickness ≥15 mm (minimal wall thickness ≥13 mm is acceptable with a positive family history of HCM or with a known disease-causing gene mutation).
• Adequate acoustic windows for echocardiography.
• For Cohorts 1, 2 and 3 has LVOT-G during screening as follows:
• Resting gradient ≥50 mmHg OR
• Resting gradient ≥30 mmHg and \<50 mmHg with post-Valsalva LVOT-G ≥50 mmHg
• For Cohort 4 has resting and post-Valsalva LVOT-G \< 30 mmHg at the time of screening
• For Cohort 4 has elevated NT-proBNP \> 300 pg/mL at the time of screening
• LVEF ≥60% at screening.
• New York Heart Association (NYHA) Class II or III at screening.
• Patients on beta-blockers, verapamil, diltiazem, or ranolazine should have been on stable doses for \>4 weeks prior to randomization and anticipate remaining on the same medication regimen during the study.
• For Cohort 3: Patients must be taking disopyramide. Patients should have been on stable disopyramide doses for \>4 weeks prior to screening and anticipate remaining on the same medication regimen during the study.

You may not qualify if:

• Aortic stenosis or fixed subaortic obstruction.
• Known infiltrative or storage disorder causing cardiac hypertrophy that mimics oHCM (eg, Noonan syndrome, Fabry disease, amyloidosis).
• History of LV systolic dysfunction (LVEF \<45%) at any time during their clinical course.
• Documented history of current obstructive coronary artery disease (\>70% stenosis in one or more epicardial coronary arteries) or documented history of myocardial infarction.
• For Cohorts 1, 2 and 4: Has been treated with disopyramide or antiarrhythmic drugs that have negative inotropic activity within 4 weeks prior to screening. (For Cohort 3, use of disopyramide is required).
• Has any ECG abnormality considered by the investigator to pose a risk to patient safety (eg, second degree atrioventricular block type II).
• Paroxysmal atrial fibrillation or flutter documented during the screening period.
• History of syncope or sustained ventricular tachyarrhythmia with exercise within 6 months prior to screening.
• Has received prior treatment with CK-3773274 or mavacamten.

Sponsors & Collaborators

• Cytokinetics: lead

Study Sites (22)

Cedar-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

UCSF Medical Center

San Francisco, California, 94143, United States

Location

Northwestern University

Evanston, Illinois, 60208, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Michigan Medicine - University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

New York University Langone Health Medical Center

New York, New York, 10016, United States

Location

Carolinas Medical Center

Charlotte, North Carolina, 28203, United States

Location

Duke Cardiology at Southpoint

Durham, North Carolina, 27713, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Hospital of the University of Pennsylvania (University of Pennsylvania School of Medicine)

Philadelphia, Pennsylvania, 19104, United States

Location

UMPC Heart and Vascular Institute

Pittsburgh, Pennsylvania, 15213, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

Intermountain Medical Center

Murray, Utah, 84107, United States

Location

University of Virginia Health System

Charlottesville, Virginia, 22903, United States

Location

Azienda Ospedaliero Universitaria Careggi

Florence, Italy

Location

Erasmus University Medical Center (Erasmus MC)

Rotterdam, Netherlands

Location

Complejo Hospitalario Universitario A Coruña

A Coruña, 15003, Spain

Location

Hospital Universitario Puerta de Hierro de Majadahonda

Madrid, Spain

Location

Related Publications (2)

• Masri A, Sherrid MV, Abraham TP, Choudhury L, Garcia-Pavia P, Kramer CM, Barriales-Villa R, Owens AT, Rader F, Nagueh SF, Olivotto I, Saberi S, Tower-Rader A, Wong TC, Coats CJ, Watkins H, Fifer MA, Solomon SD, Heitner SB, Jacoby DL, Kupfer S, Malik FI, Meng L, Sohn RL, Wohltman A, Maron MS; REDWOOD-HCM Investigators. Efficacy and Safety of Aficamten in Symptomatic Nonobstructive Hypertrophic Cardiomyopathy: Results From the REDWOOD-HCM Trial, Cohort 4. J Card Fail. 2024 Nov;30(11):1439-1448. doi: 10.1016/j.cardfail.2024.02.020. Epub 2024 Mar 15.

  PMID: 38493832 DERIVED

• Zampieri M, Argiro A, Marchi A, Berteotti M, Targetti M, Fornaro A, Tomberli A, Stefano P, Marchionni N, Olivotto I. Mavacamten, a Novel Therapeutic Strategy for Obstructive Hypertrophic Cardiomyopathy. Curr Cardiol Rep. 2021 Jun 3;23(7):79. doi: 10.1007/s11886-021-01508-0.

  PMID: 34081217 DERIVED

MeSH Terms

Conditions

Cardiomyopathy, Hypertrophic

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: MD Cytokinetics
• Organization: Cytokinetics, Inc

medicalaffairs@cytokinetics.com

650-624-2929

Study Officials

• Cytokinetics, MD

  Cytokinetics

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 3, 2020
• First Posted: January 7, 2020
• Study Start: January 10, 2020
• Primary Completion: February 28, 2023
• Study Completion: February 28, 2023
• Last Updated: February 24, 2026
• Results First Posted: February 24, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1); US (18); IT (1); ES (2)