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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
525
Cardurion Investigative Site
Pasadena, California, United States
RECRUITINGCardurion Investigative Site
Bloomfield Hills, Michigan, United States
RECRUITINGChange 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
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
Left ventricular end-systolic volume index
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Change from baseline in left ventricular end-systolic volume index (LVESVI, measured in mL/m²) at 12 and 24 weeks
Time frame: Baseline, Week 12, and Week 24
Early diastolic mitral inflow velocity (E)/early diastolic mitral annular velocity (e') ratio
Change from baseline in early diastolic mitral inflow velocity (E)/early diastolic mitral annular velocity (e') ratio (E/e' ratio, unitless) at 12 and 24 weeks
Time frame: Baseline, Week 12, and Week 24
Global longitudinal strain
Change from baseline in global longitudinal strain (GLS, measured in %) at 12 and 24 weeks
Time frame: Baseline, Week 12, and Week 24
Left atrial volume index
Change from baseline in left atrial volume index (LAVI, measured in mL/m²) at 12 and 24 weeks
Time frame: Baseline, Week 12, and Week 24
Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical summary score
Change from baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical summary score (CSS) at 12 and 24 weeks. a. KCCQ, scored 0 to 100 with higher scores indicating better health.
Time frame: Baseline, Week 12 and Week 24
Kansas City Cardiomyopathy Questionnaire (KCCQ) Total summary score
Change from baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Total summary score (TSS) at 12 and 24 weeks. a. KCCQ scored 0 to 100 with higher scores indicating better health.
Time frame: Baseline, Week 12, and Week 24
Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall summary score
Change from baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall summary score (OSS) at 12 and 24 weeks. KCCQ, scored 0 to 100 with higher scores indicating better health.
Time frame: Baseline, Week 12, and Week 24