Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled Safety and Efficacy Study of CDR132L on Reverse Cardiac Remodeling in Patients With Heart Failure With Mildly Reduced or Preserved Ejection Fraction and Cardiac Hypertrophy
Overview
- Phase
- Phase 2
- Intervention
- CDR132L
- Conditions
- Heart Failure With Preserved Ejection Fraction
- Sponsor
- Cardior Pharmaceuticals GmbH
- Primary Endpoint
- Left atrial maximum volume
- Status
- Withdrawn
- Last Updated
- 3 months ago
Overview
Brief Summary
This is a Phase 2, multicenter, randomized, double-blind, placebo-controlled study including approximately 130 randomized HF patients with heart failure with mildly reduced or preserved ejection fraction (LVEF ≥45%), to assess efficacy and safety of CDR132L on reverse remodeling. In this study, patients with HFpEF (EF ≥50%) or HFmrEF (LVEF 45-49%) will be included.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Main Inclusion Criteria:
- •Provision of signed informed consent prior to any study-specific procedures.
- •Male or female of non-childbearing potential patients age ≥40 and \<85 years.
- •Documented diagnosis of symptomatic heart failure (NYHA class II-IV) at enrollment, and a medical history of typical symptoms/signs of heart failure ≥6 weeks before enrollment with at least intermittent need for diuretic treatment.
- •Ejection fraction ≥ 45% (determined by echocardiography at site laboratory)
- •Increased intraventricular wall thickness (≥11 mm for female and ≥12 mm for male patients by echocardiography at site laboratory)
- •NT-proBNP \> 300 pg/ml (sinus rhythm); \>900 pg/ml (atrial fibrillation at time of screening/inclusion or documented with the last 6 months)
- •BMI between 22 kg/m² and 45 kg/m².
Exclusion Criteria
- •Hemoglobin A1C (A1C) ≥10.5%
- •eGFR \<35 mL/min/1.73m²
- •Systolic blood pressure (BP) \<90 mmHg on 2 consecutive measurements at 5-minute intervals, at Screening.
- •Systolic BP≥180 mmHg on 2 consecutive measurements at 5-minute intervals, at Screening.
- •Planned coronary revascularization, ablation of atrial flutter/fibrillation and valve repair/replacement.
- •Stroke or transient ischemic attack (TIA) within 12 weeks prior to enrolment.
Arms & Interventions
CDR132L 4.52 mg
Six times CDR132L 4.52 mg/kg body weight intravenous in single dose.
Intervention: CDR132L
Placebo
Six times Placebo intravenous in single dose.
Intervention: Placebo
Outcomes
Primary Outcomes
Left atrial maximum volume
Time Frame: 6 months
Left atrial maximum volume (measured by cardiac magnetic resonance imaging in end systole(indexed to the height in meters raised to the power of 2))
Total cardiac extracellular volume
Time Frame: 6 months
Total cardiac extracellular volume (mL) measured by cardiac magnetic resonance imaging
Left atrial strain
Time Frame: 6 months
Left atrial strain measured by cardiac magnetic resonance imaging
Concentration of N-terminal pro B-type natriuretic peptide
Time Frame: 6 months
Concentration measured as biomarker from blood samples.
Maximum left ventricular wall thickness
Time Frame: 6 months
Maximum left ventricular wall thickness measured by cardiac magnetic resonance imaging
Age-adjusted e' velocity
Time Frame: 6 months
Age-adjusted e' velocity measured by doppler echocardiography. With e´velocity being the maximal velocity of mitral annular motion (E-wave).
Concentration of high-sensitivity cardiac troponin T
Time Frame: 6 months
Concentration measured as biomarker from blood samples.
Left ventricular mass
Time Frame: 6 months
Left ventricular mass measured by cardiac magnetic resonance imaging (indexed to the height in meters raised to the power of 2)
Global longitudinal strain
Time Frame: 6 months
Global longitudinal strain measured by echocardiography
E/e'
Time Frame: 6 months
E/e' measured by doppler echocardiography to evaluate the LV filling pressure.