AMBER-HFpEF: Assessment of CK-4021586 in a Multi-Center, Blinded Evaluation of Safety and Tolerability Results in HFpEF

NCT06793371 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: CY 90212024-516349-38-00
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 24

Brief Summary

This is a Phase 2 dose-finding study in adult participants with symptomatic HFpEF.

Conditions

Symptomatic Heart Failure With Preserved Ejection Fraction (HFpEF)

Keywords

Symptomatic heart failure with preserved ejection fraction; HFpEF; Heart failure; CK-4021586; CK-586; AMBER-HFpEF; AMBER; Cardiac myosin inhibitor; CMI; CY 9021; ulacamten

Outcome Measures

Primary Outcomes (3)

• Incidence of early drug discontinuation

  Incidence of early drug discontinuation observed during dosing of CK 4021586 in patients with HFpEF

  12 weeks

• Incidence of LVEF < 40%

  Incidence of left-ventricular ejection fraction (LVEF) \< 40% observed during dosing of CK-4021586 in patients with HFpEF

  12 weeks

• Incidence of AEs

  Incidence of adverse events observed during dosing of CK-4021586 in patients with HFpEF

  12 weeks

Secondary Outcomes (5)

• Change in NT-proBNP

  Baseline to Week 6 and Week 12

• Plasma concentrations of CK-4021586

  12 weeks

• Concentration-response relationship of CK-4021586 on NT-proBNP change

  Baseline to Week 12

• Concentration-response relationship of CK-4021586 to LVEF change

  Baseline to Week 12

• Change in LVEF

  Baseline to Week 6 and Week 12

Study Arms (6)

CK-4021586 - Cohort 1

EXPERIMENTAL

Participants may receive 150 mg or 300 mg of CK-4021586 daily, guided by echocardiography assessments, for 12 weeks total.

Drug: CK-4021586 (150 mg, 300 mg, 450 mg, and 600 mg)

Placebo - Cohort 1

PLACEBO COMPARATOR

Participants will receive placebo daily for up to 12 weeks.

Drug: Placebo to match CK-4021586

CK-4021586 - Cohort 2

EXPERIMENTAL

Participants may receive 300 mg or 450 mg of CK-4021586 daily, guided by echocardiography assessments, for 12 weeks total.

Drug: CK-4021586 (150 mg, 300 mg, 450 mg, and 600 mg)

Placebo - Cohort 2

PLACEBO COMPARATOR

Participants will receive placebo daily for up to 12 weeks.

Drug: Placebo to match CK-4021586

CK-4021586 - Cohort 3

EXPERIMENTAL

Participants may receive 450 mg or 600 mg of CK-4021586 daily, guided by echocardiography assessments, for 12 weeks total.

Drug: CK-4021586 (150 mg, 300 mg, 450 mg, and 600 mg)

Placebo - Cohort 3

PLACEBO COMPARATOR

Participants will receive placebo daily for up to 12 weeks.

Drug: Placebo to match CK-4021586

Interventions

Placebo to match CK-4021586 DRUG

Placebo administered orally

Placebo - Cohort 1; Placebo - Cohort 2; Placebo - Cohort 3

CK-4021586 (150 mg, 300 mg, 450 mg, and 600 mg) DRUG

CK-4021586 administered orally

Also known as: ulacamten

CK-4021586 - Cohort 1; CK-4021586 - Cohort 2; CK-4021586 - Cohort 3

Eligibility Criteria

• Age: 40 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females ≥ 40 years and ≤ 85 years of age at screening.
• Diagnosed with HF with NYHA functional class II or III.
• Screening echocardiography with LVEF ≥ 60%.
• Screening NT-proBNP ≥ 300 pg/mL for participants in sinus rhythm and ≥ 900 pg/mL for participants with comorbid atrial fibrillation or flutter.
• Body mass index \< 40 kg/m2.
• Participants on beta-blockers, angiotensin-converting enzyme (ACE)/angiotensin II receptor blocker (ARB) or angiotensin receptor/neprilysin inhibitor (ARNI), must be on stable doses for more than 30 days prior to screening.
• Participants on a glucagon-like peptide-1 (GLP-1) agonist must be on a stable dose for more than 24 weeks prior to screening with no anticipated plans to change dose during this study.

You may not qualify if:

• History or evidence of any other clinically significant disorder, malignancy, active infection, other condition, or disease that, in the opinion of the investigator or the Medical Monitor, would pose a risk to patient safety or interfere with the study evaluation, procedures, or completion.

Sponsors & Collaborators

• Cytokinetics: lead

Study Sites (24)

Eastern Shore Research Institute, LLC

Fairhope, Alabama, 36532, United States

RECRUITING

University of Arizona Sarver Heart Center

Tucson, Arizona, 85724, United States

RECRUITING

John L. McClellan Memorial Veterans Hospital

Little Rock, Arkansas, 72205, United States

RECRUITING

BioSolutions Clinical Research Center

Imperial, California, 92251, United States

RECRUITING

Profound Research LLC

Pasadena, California, 91105, United States

RECRUITING

University of California, San Francisco - Heart and Vascular Center

San Francisco, California, 94143, United States

RECRUITING

FOMAT - Comprehensive Cardiovascular Care

Santa Maria, California, 93454, United States

RECRUITING

Blue Coast Research Center, LLC

Vista, California, 92081, United States

RECRUITING

New Generation of Medical Research

Hialeah, Florida, 33016, United States

RECRUITING

Cleveland Clinic Florida

Weston, Florida, 33331, United States

RECRUITING

Methodist Medical Center of Illinois

Peoria, Illinois, 61636, United States

RECRUITING

Louisiana Heart Center

Slidell, Louisiana, 70458, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02214, United States

RECRUITING

Mayo Clinic

Rochester, Minnesota, 55905, United States

RECRUITING

Washington University Center for Advanced Medicine

St Louis, Missouri, 63110, United States

RECRUITING

Morristown Medical Center

Morristown, New Jersey, 07960, United States

RECRUITING

NYU Langone Health

New York, New York, 10016, United States

RECRUITING

The Lindner Center for Research & Education at The Christ Hospital

Cincinnati, Ohio, 45219, United States

RECRUITING

Oregon Health and Science University

Portland, Oregon, 97239, United States

RECRUITING

University of Texas Southwestern Medical Center, Dallas

Dallas, Texas, 75390, United States

RECRUITING

Center for Advanced Heart Failure

Houston, Texas, 77030, United States

RECRUITING

DelRicht Research

Vienna, Virginia, 22182, United States

RECRUITING

Swedish Heart & Vascular Institute, Advanced Cardiac Support Program

Seattle, Washington, 98122, United States

RECRUITING

Froedtert Hospital - Center for Advanced Care

Milwaukee, Wisconsin, 53226, United States

RECRUITING

MeSH Terms

Conditions

Heart Failure

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Officials

• Cytokinetics MD

  Cytokinetics

  STUDY DIRECTOR

Central Study Contacts

Cytokinetics MD

CONTACT

650-624-2929; medicalaffairs@cytokinetics.com

Study Design

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

Study Record Dates

• First Submitted: January 21, 2025
• First Posted: January 27, 2025
• Study Start: February 6, 2025
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: January 12, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (24)