Reverse Remodeling Effects of CDR132L in Patients With Heart Failure With Mildly Reduced or Preserved Ejection Fraction and Cardiac Hypertrophy

Heart Failure With Preserved Ejection Fraction Clinical Trial

— REMOD-REVERT  

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT05953831
• Other study ID #: CDR132L-P2-06
• Status: Withdrawn
• Phase: Phase 2
• Start date: April 2024
• Est. completion date: September 2025

Study information

• Verified date: June 2024
• Source: Cardior Pharmaceuticals GmbH
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: September 2025
• Est. primary completion date: September 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 85 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cardiomegaly
• Heart Failure
• Heart Failure With Preserved Ejection Fraction
• Hypertrophy

Intervention

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
Placebo to CDR132L

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Cardior Pharmaceuticals GmbH

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Left ventricular mass	Left ventricular mass measured by cardiac magnetic resonance imaging (indexed to the height in meters raised to the power of 2)	6 months
Primary	Left atrial maximum volume	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))	6 months
Primary	Total cardiac extracellular volume	Total cardiac extracellular volume (mL) measured by cardiac magnetic resonance imaging	6 months
Primary	Left atrial strain	Left atrial strain measured by cardiac magnetic resonance imaging	6 months
Primary	Maximum left ventricular wall thickness	Maximum left ventricular wall thickness measured by cardiac magnetic resonance imaging	6 months
Primary	Age-adjusted e' velocity	Age-adjusted e' velocity measured by doppler echocardiography. With e´velocity being the maximal velocity of mitral annular motion (E-wave).	6 months
Primary	Global longitudinal strain	Global longitudinal strain measured by echocardiography	6 months
Primary	E/e'	E/e' measured by doppler echocardiography to evaluate the LV filling pressure.	6 months
Primary	Concentration of N-terminal pro B-type natriuretic peptide	Concentration measured as biomarker from blood samples.	6 months
Primary	Concentration of high-sensitivity cardiac troponin T	Concentration measured as biomarker from blood samples.	6 months