Reverse Remodeling Effects of CDR132L in Patients With Heart Failure With Mildly Reduced or Preserved Ejection Fraction and Cardiac Hypertrophy (REMOD-REVERT)

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Heart Failure With Preserved Ejection Fraction
• Intervention / Treatment: Drug: CDR132L; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 130
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Cardior Clinical Team; Phone Number: 30 +49511338599; Email: clinical@cardior.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
Total cardiac extracellular volume	Total cardiac extracellular volume (mL) measured by cardiac magnetic resonance imaging	6 months
Left atrial strain	Left atrial strain measured by cardiac magnetic resonance imaging	6 months
Maximum left ventricular wall thickness	Maximum left ventricular wall thickness measured by cardiac magnetic resonance imaging	6 months
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
Global longitudinal strain	Global longitudinal strain measured by echocardiography	6 months
E/e'	E/e' measured by doppler echocardiography to evaluate the LV filling pressure.	6 months
Concentration of N-terminal pro B-type natriuretic peptide	Concentration measured as biomarker from blood samples.	6 months
Concentration of high-sensitivity cardiac troponin T	Concentration measured as biomarker from blood samples.	6 months

Collaborators and Investigators

• Sponsor: Cardior Pharmaceuticals GmbH

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): September 1, 2025
• Study Completion (Estimated): September 1, 2025

Study Registration Dates

• First Submitted: June 29, 2023
• First Submitted That Met QC Criteria: July 18, 2023
• First Posted (Actual): July 20, 2023

Study Record Updates

• Last Update Posted (Estimated): January 8, 2024
• Last Update Submitted That Met QC Criteria: January 5, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Heart failure; HFpEF; Cardiac Hypertrophy
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Pathological Conditions, Anatomical; Heart Failure; Hypertrophy; Cardiomegaly
• Other Study ID Numbers: CDR132L-P2-06

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No