A Trial of CRD-4730 in HFrEF

Официальное название

A Phase 2, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Efficacy, Safety, and Tolerability of CRD-4730 in Patients With Heart Failure With Reduced Ejection Fraction (HFrEF)

Обзор

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.

Вмешательства

• Препарат CRD-4730
  Experimental, Dose A, B and C
• Препарат Placebo
  Placebo

Первичные конечные точки

• Change from Baseline in Composite Z-Score at 24 weeks [Срок оценки: Baseline and Week 24]

Вторичные конечные точки (11)

• NT-proBNP biomarker [Срок оценки: Baseline, Week 12, and Week 24]
• Left ventricular end-diastolic volume [Срок оценки: Baseline, Week 12, and Week 24]
• Left ventricular end-diastolic volume index [Срок оценки: Baseline, Week 12, and Week 24]
• Left ventricular end-systolic volume [Срок оценки: Baseline, Week 12, and Week 24]
• Left ventricular end-systolic volume index [Срок оценки: Baseline, Week 12, and Week 24]
• Early diastolic mitral inflow velocity (E)/early diastolic mitral annular velocity (e') ratio [Срок оценки: Baseline, Week 12, and Week 24]
• Global longitudinal strain [Срок оценки: Baseline, Week 12, and Week 24]
• Left atrial volume index [Срок оценки: Baseline, Week 12, and Week 24]
• Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical summary score [Срок оценки: Baseline, Week 12 and Week 24]
• Kansas City Cardiomyopathy Questionnaire (KCCQ) Total summary score [Срок оценки: Baseline, Week 12, and Week 24]
• Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall summary score [Срок оценки: Baseline, Week 12, and Week 24]

Критерии участия

Критерии включения

• 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).

Критерии исключения

• 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/Exclusion criteria may apply.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Лечение

Центры проведения

США · 2 центра

• Cardurion Investigative Site — Pasadena
• Cardurion Investigative Site — Bloomfield Hills

Публикации

• 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

Идентификаторы

NCT: NCT07750873 · CRD-4730-210

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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