REMOD-REVERT: Reverse Remodeling Effects of CDR132L in Patients With Heart Failure With Mildly Reduced or Preserved Ejection Fraction and Cardiac Hypertrophy
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: CDR132L 4.52 mg Six times CDR132L 4.52 mg/kg body weight intravenous in single dose. |
Drug: CDR132L
CDR132L is a synthetic antisense oligonucleotide (ASO) and a selective inhibitor of microRNA-132-3p (miR-132). miR-132 in cardiomyocytes is a central switch affecting the expression of genes that are crucially involved in maladaptive cardiac remodeling, transformation, and pathological cardiac growth (hypertrophy), contributing to adverse cardiac remodeling and heart failure (HF).1-5 Aberrant expression of miR-132 in cardiac cells is causally associated with cardiac remodeling and HF progression.
|
| Placebo Comparator: Placebo Six times Placebo intravenous in single dose. |
Drug: Placebo
Placebo to CDR132L
|
Outcome Measures
Primary Outcome Measures
- Left ventricular mass [6 months]
Left ventricular mass measured by cardiac magnetic resonance imaging (indexed to the height in meters raised to the power of 2)
- Left atrial maximum volume [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 [6 months]
Total cardiac extracellular volume (mL) measured by cardiac magnetic resonance imaging
- Left atrial strain [6 months]
Left atrial strain measured by cardiac magnetic resonance imaging
- Maximum left ventricular wall thickness [6 months]
Maximum left ventricular wall thickness measured by cardiac magnetic resonance imaging
- Age-adjusted e' velocity [6 months]
Age-adjusted e' velocity measured by doppler echocardiography. With e´velocity being the maximal velocity of mitral annular motion (E-wave).
- Global longitudinal strain [6 months]
Global longitudinal strain measured by echocardiography
- E/e' [6 months]
E/e' measured by doppler echocardiography to evaluate the LV filling pressure.
- Concentration of N-terminal pro B-type natriuretic peptide [6 months]
Concentration measured as biomarker from blood samples.
- Concentration of high-sensitivity cardiac troponin T [6 months]
Concentration measured as biomarker from blood samples.
Eligibility Criteria
Criteria
Main Inclusion Criteria:
-
Provision of signed informed consent prior to any study-specific procedures.
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Male or female of non-childbearing potential patients age ≥40 and <85 years.
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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.
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Ejection fraction ≥ 45% (determined by echocardiography at site laboratory)
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Increased intraventricular wall thickness (≥11 mm for female and ≥12 mm for male patients by echocardiography at site laboratory)
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NT-proBNP > 300 pg/ml (sinus rhythm); >900 pg/ml (atrial fibrillation at time of screening/inclusion or documented with the last 6 months)
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BMI between 22 kg/m² and 45 kg/m².
Main Exclusion Criteria:
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Hemoglobin A1C (A1C) ≥10.5%
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eGFR <35 mL/min/1.73m²
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Systolic blood pressure (BP) <90 mmHg on 2 consecutive measurements at 5-minute intervals, at Screening.
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Systolic BP≥180 mmHg on 2 consecutive measurements at 5-minute intervals, at Screening.
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Planned coronary revascularization, ablation of atrial flutter/fibrillation and valve repair/replacement.
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Stroke or transient ischemic attack (TIA) within 12 weeks prior to enrolment.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Cardior Pharmaceuticals GmbH
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CDR132L-P2-06