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

A Multi-Center, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of CK-4021586 in Adults With Symptomatic Heart Failure With Preserved Ejection Fraction

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

Study Overview

• Status: Recruiting
• Conditions: Symptomatic Heart Failure With Preserved Ejection Fraction (HFpEF)
• Intervention / Treatment: Drug: CK-4021586 (150 mg, 300 mg, 450 mg, and 600 mg); Drug: Placebo to match CK-4021586

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Cytokinetics MD; Phone Number: 650-624-2929; Email: medicalaffairs@cytokinetics.com

Study Locations

• United States
  • Alabama
    • Fairhope, Alabama, United States, 36532
      • Recruiting
      • Eastern Shore Research Institute, LLC
  • Arizona
    • Tucson, Arizona, United States, 85724
      • Recruiting
      • University of Arizona Sarver Heart Center
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Recruiting
      • John L. McClellan Memorial Veterans Hospital
  • California
    • Imperial, California, United States, 92251
      • Recruiting
      • Biosolutions Clinical Research Center
    • Pasadena, California, United States, 91105
      • Recruiting
      • Profound Research LLC
    • San Francisco, California, United States, 94143
      • Recruiting
      • University of California, San Francisco - Heart and Vascular Center
    • Santa Maria, California, United States, 93454
      • Recruiting
      • FOMAT - Comprehensive Cardiovascular Care
    • Vista, California, United States, 92081
      • Recruiting
      • Blue Coast Research Center, LLC
  • Florida
    • Hialeah, Florida, United States, 33016
      • Recruiting
      • New Generation of Medical Research
    • Weston, Florida, United States, 33331
      • Recruiting
      • Cleveland Clinic Florida
  • Illinois
    • Peoria, Illinois, United States, 61636
      • Recruiting
      • Methodist Medical Center of Illinois
  • Louisiana
    • Slidell, Louisiana, United States, 70458
      • Recruiting
      • Louisiana Heart Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02214
      • Recruiting
      • Massachusetts General Hospital
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University Center for Advanced Medicine
  • New Jersey
    • Morristown, New Jersey, United States, 07960
      • Recruiting
      • Morristown Medical Center
  • New York
    • New York, New York, United States, 10016
      • Recruiting
      • NYU Langone Health
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Recruiting
      • The Lindner Center for Research & Education at The Christ Hospital
  • Oregon
    • Portland, Oregon, United States, 97239
      • Recruiting
      • Oregon Health and Science University
  • Texas
    • Dallas, Texas, United States, 75390
      • Recruiting
      • University of Texas Southwestern Medical Center, Dallas
    • Houston, Texas, United States, 77030
      • Recruiting
      • Center for Advanced Heart Failure
  • Virginia
    • Vienna, Virginia, United States, 22182
      • Recruiting
      • DelRicht Research
  • Washington
    • Seattle, Washington, United States, 98122
      • Recruiting
      • Swedish Heart & Vascular Institute, Advanced Cardiac Support Program
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Recruiting
      • Froedtert Hospital - Center for Advanced Care

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.
• Other protocol-defined Inclusion/Exclusion criteria apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CK-4021586 - Cohort 1; 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); CK-4021586 administered orally; Other Names: ulacamten
Placebo Comparator: Placebo - Cohort 1; Participants will receive placebo daily for up to 12 weeks.	Drug: Placebo to match CK-4021586; Placebo administered orally
Experimental: CK-4021586 - Cohort 2; 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); CK-4021586 administered orally; Other Names: ulacamten
Placebo Comparator: Placebo - Cohort 2; Participants will receive placebo daily for up to 12 weeks.	Drug: Placebo to match CK-4021586; Placebo administered orally
Experimental: CK-4021586 - Cohort 3; 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); CK-4021586 administered orally; Other Names: ulacamten
Placebo Comparator: Placebo - Cohort 3; Participants will receive placebo daily for up to 12 weeks.	Drug: Placebo to match CK-4021586; Placebo administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in NT-proBNP	Change from baseline values in NT-proBNP to Week 6 and Week 12	Baseline to Week 6 and Week 12
Plasma concentrations of CK-4021586	Observed 2-hour post dose plasma concentration (C2hr) and minimum plasma concentration (Cmin) for CK-4021586 over the dosing interval	12 weeks
Concentration-response relationship of CK-4021586 on NT-proBNP change	Slope of the relationship of plasma concentration of CK-4021586 to the change from baseline in the NT-proBNP	Baseline to Week 12
Concentration-response relationship of CK-4021586 to LVEF change	Slope of the relationship of plasma concentration of CK-4021586 to the change from baseline in the LVEF	Baseline to Week 12
Change in LVEF	Change from baseline in LVEF at Week 6 and Week 12	Baseline to Week 6 and Week 12

Collaborators and Investigators

• Sponsor: Cytokinetics
• Investigators: Study Director: Cytokinetics MD, Cytokinetics

Study record dates

Study Major Dates

• Study Start (Actual): February 6, 2025
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: January 21, 2025
• First Submitted That Met QC Criteria: January 21, 2025
• First Posted (Actual): January 27, 2025

Study Record Updates

• Last Update Posted (Estimated): January 12, 2026
• Last Update Submitted That Met QC Criteria: January 8, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Heart failure; CMI; HFpEF; AMBER; CK-586; CK-4021586; Symptomatic heart failure with preserved ejection fraction; AMBER-HFpEF; Cardiac myosin inhibitor; CY 9021; ulacamten
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Failure
• Other Study ID Numbers: CY 9021; 2024-516349-38-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No