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

NCT05953831 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: CDR132L-P2-06
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Heart Failure With Preserved Ejection Fraction

Keywords

HFpEF; Heart failure; Cardiac Hypertrophy

Outcome Measures

Primary Outcomes (10)

• 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

Study Arms (2)

CDR132L 4.52 mg

EXPERIMENTAL

Six times CDR132L 4.52 mg/kg body weight intravenous in single dose.

Drug: CDR132L

Placebo

PLACEBO COMPARATOR

Six times Placebo intravenous in single dose.

Drug: Placebo

Interventions

CDR132L DRUG

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.

CDR132L 4.52 mg

Placebo DRUG

Placebo to CDR132L

Placebo

Eligibility Criteria

• Age: 40 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• BMI between 22 kg/m² and 45 kg/m².

You may not qualify if:

• 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.

Sponsors & Collaborators

• Cardior Pharmaceuticals GmbH: lead

MeSH Terms

Conditions

Heart Failure; Cardiomegaly

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Hypertrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: IMP to be masked after preparation by unblinded staff.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 29, 2023
• First Posted: July 20, 2023
• Study Start: April 1, 2024
• Primary Completion: September 1, 2025
• Study Completion: September 1, 2025
• Last Updated: January 9, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share