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

Phase 2

Recruiting

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

• Registration Number: NCT06793371
• Lead Sponsor: Cytokinetics

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2025-01-21
• Study First Submitted QC: 2025-01-21
• Study First Posted: 2025-01-27
• Study Start: 2025-02-06
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-20
• Last Update Posted: 2025-05-23
• Primary Completion: 2026-09
• Study Completion: 2026-09

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 60

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), or sodium-glucose contransporter-2 (SGLT2)-inhibitors must be on stable doses for more than 4 weeks 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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CK-4021586 - Cohort 1	CK-4021586 (150 mg, 300 mg, 450 mg, and 600 mg)	Participants may receive 150 mg or 300 mg of CK-4021586 daily, guided by echocardiography assessments, for 12 weeks total.
Placebo - Cohort 2	Placebo to match CK-4021586	Participants will receive placebo daily for up to 12 weeks.
CK-4021586 - Cohort 3	CK-4021586 (150 mg, 300 mg, 450 mg, and 600 mg)	Participants may receive 450 mg or 600 mg of CK-4021586 daily, guided by echocardiography assessments, for 12 weeks total.
Placebo - Cohort 3	Placebo to match CK-4021586	Participants will receive placebo daily for up to 12 weeks.
Placebo - Cohort 1	Placebo to match CK-4021586	Participants will receive placebo daily for up to 12 weeks.
CK-4021586 - Cohort 2	CK-4021586 (150 mg, 300 mg, 450 mg, and 600 mg)	Participants may receive 300 mg or 450 mg of CK-4021586 daily, guided by echocardiography assessments, for 12 weeks total.

Primary Outcome Measures

Name	Time	Method
Incidence of early drug discontinuation	12 weeks	Incidence of early drug discontinuation observed during dosing of CK 4021586 in patients with HFpEF
Incidence of LVEF < 40%	12 weeks	Incidence of left-ventricular ejection fraction (LVEF) \< 40% observed during dosing of CK-4021586 in patients with HFpEF
Incidence of AEs	12 weeks	Incidence of adverse events observed during dosing of CK-4021586 in patients with HFpEF

Secondary Outcome Measures

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

Trial Locations

Locations (5)

Eastern Shore Research Institute, LLC; 🇺🇸 Fairhope, Alabama, United States

Morristown Medical Center; 🇺🇸 Morristown, New Jersey, United States

The Lindner Center for Research & Education at The Christ Hospital; 🇺🇸 Cincinnati, Ohio, United States

Oregon Health and Science University; 🇺🇸 Portland, Oregon, United States

University of Texas Southwestern Medical Center, Dallas; 🇺🇸 Dallas, Texas, United States