A Trial of CRD-4730 in HFrEF

ConditionHeart Failure With Reduced Ejection Fraction (HFrEF)

Trial statusRecruiting

Trial phasePhase 2

Trial typeInterventional

Biological sexAll

Age18-85

SponsorCardurion Pharmaceuticals, Inc.

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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).

Disqualifiers

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.

Trial design

Design model

Parallel

Treatments tested in this trial

CRD-4730
Drug
Experimental, Dose A, B and C
Placebo
Drug
Placebo

Treatment groups

525 Participants

are divided into 4 treatment groups

Group A: Study Arm 1: CRD-4730 Dose A tabletExperimental treatment 1 intervention

Group B: Study Arm 2: CRD-4730 Dose B tabletExperimental treatment 1 intervention

Group C: Study Arm 3: CRD-4730 Dose C tabletExperimental treatment 1 intervention

Group D: Study Arm 4: Matched Placebo tabletPlacebo comparator 1 intervention

Trial outcomes

Primary outcomes

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.

Time frame

Baseline and Week 24

Secondary outcomes

NT-proBNP biomarker

Change in NT-proBNP (measured in pg/mL) from baseline at 12 and 24 weeks.

Time frame

Baseline, Week 12, and Week 24

Left ventricular end-diastolic volume

Change from baseline in left ventricular end-diastolic volume (LVEDV, measured in mL) at 12 and 24 weeks

Time frame

Baseline, Week 12, and Week 24

Left ventricular end-diastolic volume index

Change from baseline in left ventricular end-diastolic volume index (LVEDVI, measured in mL/m²) at 12 and 24 weeks

Time frame

Baseline, Week 12, and Week 24

Left ventricular end-systolic volume

Change from baseline in left ventricular end-systolic volume (LVESV, measured in mL) at 12 and 24 weeks

Time frame

Baseline, Week 12, and Week 24

Other outcomes

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

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

Time frame

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

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Cardurion Pharmaceuticals, Inc.

Lead sponsor

Source ClinicalTrials.gov

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