Heart Failure With Preserved Ejection Fraction
Conditions
Keywords
HFpEF, Heart failure, Cardiac Hypertrophy
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.
Interventions
DRUGCDR132L
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.
DRUGPlacebo
Placebo to CDR132L
Sponsors
Cardior Pharmaceuticals GmbH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
IMP to be masked after preparation by unblinded staff.
Eligibility
Sex/Gender
ALL
Age
40 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
Main Inclusion Criteria: 1. Provision of signed informed consent prior to any study-specific procedures. 2. Male or female of non-childbearing potential patients age ≥40 and \<85 years. 3. 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. 4. Ejection fraction ≥45% (determined by echocardiography at site laboratory) 5. Increased intraventricular wall thickness (≥11 mm for female and ≥12 mm for male patients by echocardiography at site laboratory) 6. NT-proBNP \> 300 pg/ml (sinus rhythm); \>900 pg/ml (atrial fibrillation at time of screening/inclusion or documented with the last 6 months) 7. BMI between 22 kg/m² and 45 kg/m². Main
Exclusion criteria
1. Hemoglobin A1C (A1C) ≥10.5% 2. eGFR \<35 mL/min/1.73m² 3. Systolic blood pressure (BP) \<90 mmHg on 2 consecutive measurements at 5-minute intervals, at Screening. 4. Systolic BP≥180 mmHg on 2 consecutive measurements at 5-minute intervals, at Screening. 5. Planned coronary revascularization, ablation of atrial flutter/fibrillation and valve repair/replacement. 6. Stroke or transient ischemic attack (TIA) within 12 weeks prior to enrolment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Outcome results
None listed