A Trial of CRD-4730 in HFrEF

NCT07750873 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: CRD-4730-210
• Study Type: interventional
• Target: 525
• Locations: 1 country
• Sites: 2

Brief Summary

CRD-4730 is a calcium/calmodulin-dependent protein kinase II (CaMKII) inhibitor. The CALIBRATE-HF trial is a Phase 2, global, multi-center, randomized, double-blind, parallel-group, placebo-controlled trial. The trial will evaluate the efficacy, safety, and tolerability of CRD-4730 in addition to guideline directed medical therapy in participants with heart failure with reduced ejection fraction (HFrEF). Participants will be randomized to 1 of 4 study groups and receive investigational study drug or placebo twice daily (BID) for 24 weeks of treatment.

Conditions

Heart Failure With Reduced Ejection Fraction (HFrEF)

Keywords

Heart failure

Outcome Measures

Primary Outcomes (1)

• Change from Baseline in Composite Z-Score at 24 weeks

  Composite Z-score calculated as the average of Z-scores for the change from baseline at 24 weeks for the following 6 endpoints: NT-proBNP (log-transformed), Left ventricular end-diastolic volume index (LVEDVI), Left ventricular end-systolic volume index (LVESVI), E/e' ratio, Global longitudinal strain (GLS), Left atrial volume index (LAVI). A z-score for each component endpoint is a standardized measure with a common scale with a mean of 0 and a standard deviation of 1. Composite z-score integrates the component z-scores to assess a participant's overall response. Lower composite z-scores indicate more favorable changes from baseline, whereas higher composite z-scores indicate less favorable changes from baseline.

  Baseline and Week 24

Secondary Outcomes (11)

• NT-proBNP biomarker

  Baseline, Week 12, and Week 24

• Left ventricular end-diastolic volume

  Baseline, Week 12, and Week 24

• Left ventricular end-diastolic volume index

  Baseline, Week 12, and Week 24

• Left ventricular end-systolic volume

  Baseline, Week 12, and Week 24

• Left ventricular end-systolic volume index

  Baseline, Week 12, and Week 24

Other Outcomes (1)

• Number and percentage of participants with Treatment-emergent adverse event (TEAEs)

  First dose of investigational drug to Week 28 (end-of-study)

Study Arms (4)

Study Arm 1: CRD-4730 Dose A tablet

EXPERIMENTAL

Participants will receive Dose A of CRD-4730 administered orally twice daily for 24 weeks

Drug: CRD-4730

Study Arm 2: CRD-4730 Dose B tablet

EXPERIMENTAL

Participants will receive Dose B of CRD-4730 administered orally twice daily for 24 weeks

Drug: CRD-4730

Study Arm 3: CRD-4730 Dose C tablet

EXPERIMENTAL

Participants will receive Dose C of CRD-4730 administered orally twice daily for 24 weeks

Drug: CRD-4730

Study Arm 4: Matched Placebo tablet

PLACEBO COMPARATOR

Participants will receive placebo administered orally twice daily for 24 weeks

Drug: Placebo

Interventions

CRD-4730 DRUG

Experimental, Dose A, B and C

Study Arm 1: CRD-4730 Dose A tablet; Study Arm 2: CRD-4730 Dose B tablet; Study Arm 3: CRD-4730 Dose C tablet

Placebo DRUG

Placebo

Study Arm 4: Matched Placebo tablet

Eligibility Criteria

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

You may qualify if:

• Adult male or female patient ≥ 18 years of age and ≤ 85 years of age at the time of screening.
• Has a medical history supporting a diagnosis of clinical chronic heart failure (HF) syndrome with a duration of at least 8 weeks prior to the time of screening and current NYHA functional class II to III (based on investigator's assessment).
• Has left ventricular ejection fraction ≤ 40% by a centrally read transthoracic echocardiogram performed during screening.
• Has NT-proBNP level ≥ 600 pg/mL (70.8 pmol/L) at the time of screening. Patients in atrial fibrillation or flutter at the time of screening are required to have an NT-proBNP level of ≥ 900 pg/mL (106.4 pmol/L).
• Is receiving optimized and stable guideline directed HF therapy (per applicable regional or national guidelines).

You may not qualify if:

• Has evidence of recent HF exacerbation defined by hospitalization or requirement for IV or SQ diuretics within 4 weeks of the time of screening or during the Screening Period.
• Has a requirement for routine, scheduled outpatient IV infusions for HF (ie, inotropes, vasodilators, or diuretics) or routinely scheduled ultrafiltration.
• Has acute coronary syndrome, unstable angina, persistent angina at rest, stroke, transient ischemic attack, cardiac, carotid or other major cardiovascular surgery, cardiac valve repair (surgical or nonsurgical) or surgical replacement, or carotid angioplasty within 8 weeks prior to screening or during the Screening Period.
• Has clinical suspicion of infiltrative cardiomyopathy (eg, amyloid, sarcoid), hypertrophic cardiomyopathy (obstructive or non-obstructive), or HF secondary to severe valvular disease, active myocarditis, active pericarditis, or clinically significant congenital heart disease.

Sponsors & Collaborators

• Cardurion Pharmaceuticals, Inc.: lead

Study Sites (2)

Cardurion Investigative Site

Pasadena, California, 91105, United States

RECRUITING

Cardurion Investigative Site

Bloomfield Hills, Michigan, 48304, United States

RECRUITING

Related Publications (1)

• Takagahara, Shuichi, et al. "Novel, Potent, and Highly Selective Calcium/Calmodulin-Dependent Protein Kinase II (CaMKII) Inhibitors Reduce Substrate Phosphorylation in Rat Hearts and Prolong Survival in a Mouse Model of Severe Heart Failure." Circulation 148.Suppl_1 (2023): A12726-A12726. https://doi.org/10.1161/circ.148.suppl_1.12726

  BACKGROUND

MeSH Terms

Conditions

Heart Failure

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Central Study Contacts

Cardurion Pharmaceuticals

CONTACT

617-863-8088; ClinicalTrialsGov@cardurion.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: July 17, 2026
• First Posted: August 6, 2026
• Study Start: July 15, 2026
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2028
• Last Updated: August 6, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)