Dose-finding Study to Evaluate the Safety, Tolerability, PK, and PD of CK-3773274 in Adults With HCM

NCT ID: NCT04219826

Last Updated: 2025-02-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

96 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-01-10

Study Completion Date

2023-02-28

Brief Summary

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

Detailed Description

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Conditions

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Hypertrophic Cardiomyopathy (HCM)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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CK-3773274 - Cohort 1 (Obstructive HCM)

Subjects will receive doses of 5 - 15 mg of CK-3773274 with dose levels guided by echocardiography assessments for up to 10 weeks

Group Type EXPERIMENTAL

CK-3773274 (5 - 15 mg)

Intervention Type DRUG

CK-3773274 tablets administered orally

Placebo - Cohort 1 (Obstructive HCM)

Subjects will receive placebo for up to 10 weeks

Group Type PLACEBO_COMPARATOR

Placebo for CK-3773274

Intervention Type DRUG

Placebo administered orally

CK-3773274 - Cohort 2 (Obstructive HCM)

Subjects will receive doses 10 - 30 mg of CK-3773274 with dose levels guided by echocardiography assessments for up to 10 weeks

Group Type EXPERIMENTAL

CK-3773274 (10 - 30 mg)

Intervention Type DRUG

CK-3773274 tablets administered orally

Placebo - Cohort 2 (Obstructive HCM)

Subjects will receive placebo for up to 10 weeks

Group Type PLACEBO_COMPARATOR

Placebo for CK-3773274

Intervention Type DRUG

Placebo administered orally

CK-3773274 & disopyramide - Cohort 3 (Obstructive HCM)

Subjects will receive doses 5 - 15 mg of CK-3773274 with dose levels guided by echocardiography assessments for up to 10 weeks while taking disopyramide

Group Type EXPERIMENTAL

CK-3773274 (5 - 15 mg)

Intervention Type DRUG

CK-3773274 tablets administered orally

CK-3773274 - Cohort 4 (non-obstructive HCM)

Subjects will receive doses of 5 - 15 mg of CK-3773274 with dose levels guided by echocardiography assessments for up to 10 weeks

Group Type EXPERIMENTAL

CK-3773274 (5 - 15 mg)

Intervention Type DRUG

CK-3773274 tablets administered orally

Interventions

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CK-3773274 (5 - 15 mg)

CK-3773274 tablets administered orally

Intervention Type DRUG

CK-3773274 (10 - 30 mg)

CK-3773274 tablets administered orally

Intervention Type DRUG

Placebo for CK-3773274

Placebo administered orally

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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.

Exclusion Criteria

* 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.
* Has been treated with septal reduction therapy (surgical myectomy or percutaneous alcohol septal ablation) or has plans for either treatment during the study period (Cohorts 1, 2, and 3 only). Patients having undergone septal reduction therapy \> 12 months prior to screening who remain symptomatic from nHCM, and who meet all other criteria for inclusion, may be enrolled in Cohort 4.
* 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.
* Paroxysmal or permanent atrial fibrillation requiring rhythm restoring treatment (eg, direct-current cardioversion, ablation procedure, or antiarrhythmic therapy) ≤6 months prior to screening. (This exclusion does not apply if atrial fibrillation has been treated with anticoagulation and adequately rate-controlled for \>6 months).
* History of syncope or sustained ventricular tachyarrhythmia with exercise within 6 months prior to screening.
* Has received prior treatment with CK-3773274 or mavacamten.
Minimum Eligible Age

18 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Cytokinetics

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Cytokinetics, MD

Role: STUDY_DIRECTOR

Cytokinetics

Locations

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Cedar-Sinai Medical Center

Los Angeles, California, United States

Site Status

UCSF Medical Center

San Francisco, California, United States

Site Status

Northwestern University

Evanston, Illinois, United States

Site Status

Tufts Medical Center

Boston, Massachusetts, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status

Michigan Medicine - University of Michigan

Ann Arbor, Michigan, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

New York University Langone Health Medical Center

New York, New York, United States

Site Status

Carolinas Medical Center

Charlotte, North Carolina, United States

Site Status

Duke Cardiology at Southpoint

Durham, North Carolina, United States

Site Status

Oregon Health and Science University

Portland, Oregon, United States

Site Status

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

Philadelphia, Pennsylvania, United States

Site Status

UMPC Heart and Vascular Institute

Pittsburgh, Pennsylvania, United States

Site Status

UT Southwestern Medical Center

Dallas, Texas, United States

Site Status

Houston Methodist Hospital

Houston, Texas, United States

Site Status

Intermountain Medical Center

Murray, Utah, United States

Site Status

University of Virginia Health System

Charlottesville, Virginia, United States

Site Status

Azienda Ospedaliero Universitaria Careggi

Florence, , Italy

Site Status

Erasmus University Medical Center (Erasmus MC)

Rotterdam, , Netherlands

Site Status

Complejo Hospitalario Universitario A Coruña

A Coruña, , Spain

Site Status

Hospital Universitario Puerta de Hierro de Majadahonda

Madrid, , Spain

Site Status

Countries

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United States Italy Netherlands Spain

References

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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.

Reference Type DERIVED
PMID: 38493832 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34081217 (View on PubMed)

Other Identifiers

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2019-002785-12

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CY 6021

Identifier Type: -

Identifier Source: org_study_id

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