Heart Failure With Reduced Ejection Fraction (HFrEF)
Conditions
Keywords
Heart failure
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.
Interventions
DRUGCRD-4730
Experimental, Dose A, B and C
DRUGPlacebo
Placebo
Sponsors
Cardurion Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* 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).
Exclusion criteria
* 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. NOTE: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline in Composite Z-Score at 24 weeks | Baseline and Week 24 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| NT-proBNP biomarker | Baseline, Week 12, and Week 24 | Change in NT-proBNP (measured in pg/mL) from baseline at 12 and 24 weeks. |
| Left ventricular end-diastolic volume | Baseline, Week 12, and Week 24 | Change from baseline in left ventricular end-diastolic volume (LVEDV, measured in mL) at 12 and 24 weeks |
| Left ventricular end-diastolic volume index | Baseline, Week 12, and Week 24 | Change from baseline in left ventricular end-diastolic volume index (LVEDVI, measured in mL/m²) at 12 and 24 weeks |
| Left ventricular end-systolic volume | Baseline, Week 12, and Week 24 | Change from baseline in left ventricular end-systolic volume (LVESV, measured in mL) at 12 and 24 weeks |
| Left ventricular end-systolic volume index | Baseline, Week 12, and Week 24 | Change from baseline in left ventricular end-systolic volume index (LVESVI, measured in mL/m²) at 12 and 24 weeks |
| Early diastolic mitral inflow velocity (E)/early diastolic mitral annular velocity (e') ratio | Baseline, Week 12, and Week 24 | 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 |
| Global longitudinal strain | Baseline, Week 12, and Week 24 | Change from baseline in global longitudinal strain (GLS, measured in %) at 12 and 24 weeks |
| Left atrial volume index | Baseline, Week 12, and Week 24 | Change from baseline in left atrial volume index (LAVI, measured in mL/m²) at 12 and 24 weeks |
| Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical summary score | Baseline, Week 12 and Week 24 | 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. |
| Kansas City Cardiomyopathy Questionnaire (KCCQ) Total summary score | Baseline, Week 12, and Week 24 | 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. |
| Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall summary score | Baseline, Week 12, and Week 24 | 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. |
Countries
United States
Contacts
CONTACTCardurion Pharmaceuticals
Outcome results
None listed