Study to Assess Efficacy and Safety of CDR132L in Patients With Reduced Left Ventricular Ejection Fraction After Myocardial Infarction (HF-REVERT)

Phase 2, Multicenter, Randomized, Parallel, 3-arm, Placebo-controlled Study to Assess Efficacy and Safety of CDR132L in Patients With Reduced Left Ventricular Ejection Fraction (≤ 45%) After Myocardial Infarction

This is a Phase 2, multicenter, randomized, parallel, 3-arm, placebo-controlled study to assess efficacy and safety of CDR132L in patients with reduced Left Ventricular Ejection Fraction (LVEF) (≤ 45%) after myocardial infarction (MI). This study consists of a screening period (to occur at least 3 days after MI diagnosis), a 6-month double-blind period, and a 6-month extension period with the End of Study (EOS) Visit at Day 360/Month 12.

Two dosages of CDR132L will be tested against placebo on their effects on patients, who just had a heart attack in addition to standard care. The aim of the study is to show that CDR132L is safe and effective to improve heart failure in such patients.

Study Overview

• Status: Active, not recruiting
• Conditions: Myocardial Infarction, Acute; Heart Failure, Left Sided
• Intervention / Treatment: Drug: CDR132L; Drug: Placebo to CDR132L

• Study Type: Interventional
• Enrollment (Actual): 294
• Phase: Phase 2

Contacts and Locations

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

Study Locations

• Czechia
  • Praha, Czechia
    • Vseobecna fakultni nemocnice v Praze
  • Praha, Czechia
    • Institut Klinicke A Experimentalni Mediciny
• Germany
  • Ahaus, Germany
    • St. Marien-Krankenhaus Ahaus
  • Dresden, Germany
    • Herzzentrum Dresden Universitätsklinik
  • Erfurt, Germany
    • Helios Klinikum Erfurt
  • Göttingen, Germany
    • Universitätsmedizin Göttingen
  • Hannover, Germany
    • Medizinische Hochschule Hannover
  • Kiel, Germany
    • Universitätsklinikum Schleswig-Holstein
  • Leverkusen, Germany
    • Klinikum Leverkusen GmbH
  • Ludwigshafen, Germany
    • Klinikum Ludwigshafen
  • Würzburg, Germany
    • Universitätsklinikum Würzburg
• Greece
  • Athen, Greece
    • "Attikon" General University Hospital
  • Athens, Greece
    • "Alexandra" General Hospital of Athens
  • Patra, Greece
    • General University Hospital of Patras "Panagia i Voitheia"
• Hungary
  • Budapest, Hungary
    • Semmelweis University
  • Gyula, Hungary
    • BMKK Pándy Kálmán
  • Hatvan, Hungary
    • BKS Research Ltd.
  • Kaposvár, Hungary
    • Somogy County Kaposi Mór Teaching Hospital
  • Nyíregyháza, Hungary
    • Medifarma-98 KFT
• Netherlands
  • 's-Hertogenbosch, Netherlands
    • Jeroen Bosch Ziekenhuis (JBZ) (Hieronymus Bosch Hospital) - locatie Den Bosch
  • Deventer, Netherlands
    • Deventer Ziekenhuis
  • Doetinchem, Netherlands
    • Slingeland Ziekenhuis
  • Ede, Netherlands
    • Gelderse Vallei Ziekenhuis
  • Leeuwarden, Netherlands
    • Medisch Centrum Leeuwarden
  • Lelystad, Netherlands
    • St. Jansdal Ziekenhuis
  • Rotterdam, Netherlands
    • Erasmus University Medical Center
  • Rotterdam, Netherlands
    • Ikazia Ziekenhuis
  • Sneek, Netherlands
    • D & A Research B.V.
  • Zutphen, Netherlands
    • Gelre Ziekenhuizen
• Poland
  • Kielce, Poland
    • Specjalistyczna Poradnia Kardiologiczna i Nadcisnienia Tetniczego
  • Kraków, Poland
    • Krakowski Szpital Specjalistyczny im. Jana Pawla II
  • Kędzierzyn-Koźle, Poland
    • Polsko Amerykanskie Kliniki Serca
  • Libiąż, Poland
    • Gabinet Internistyczno-Kardiologiczny Jacek Nowak
  • Lublin, Poland
    • One wojskowy Szpital Kliniczny w Lublinie
  • Oświęcim, Poland
    • Medicome Sp. z o.o.
  • Przemyśl, Poland
    • Wojewodzki Szpital im. Sw. Ojca Pio w Przemyslu
  • Sopot, Poland
    • NZOZ Pro-Cordis Sopockie Centrum Bad. Kardiolog
  • Toruń, Poland
    • Wojewodzki Szpital Zespolony
  • Wałbrzych, Poland
    • Spec.Szpital im.dr Sokolowskiego
  • Wrocław, Poland
    • Investigational Site
  • Łódź, Poland
    • NZOZ SALUS JZ Peruga
• Spain
  • Badalona, Spain
    • Hospital Universitari Germans Trias i Pujol
  • Barcelona, Spain
    • Hospital de la Santa Creu i Sant Pau
  • Granada, Spain
    • Hospital Universitario San Cecilio
  • Madrid, Spain
    • Hospital Universitario La Paz
  • Murcia, Spain
    • Hospital Universitario Virgen de la Arrixaca
  • Sabadell, Spain
    • Hospital Universitario de Sabadell
  • Sevilla, Spain
    • Hospital Universitario Virgen Macarena
  • Valencia, Spain
    • Hospital Clínico Universitario de Valencia
  • Vigo, Spain
    • Complejo Hospitalario Universitario de Vigo
• United Kingdom
  • Glasgow, United Kingdom
    • Queen Elizabeth University Hospital
  • High Wycombe, United Kingdom
    • Wycombe Hospital
  • London, United Kingdom
    • Richmond Pharmacology Limited
  • Middlesbrough, United Kingdom
    • South Tees Hospital NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Main Inclusion Criteria:

1. Male or female patients, aged ≥ 30 to ≤ 80 years at the date of signing informed consent which is defined as the beginning of the Screening Period.
2. Spontaneous acute mycardial infarction (AMI) (type I) based on the universal MI definition with randomization to occur no later than 14 days after index event diagnosis.
3. Patient with a LVEF ≤ 45% as measured by ECHO after MI diagnosis (STEMI or NSTEMI).
4. Patient with previous MI events in history can be included.
5. Patient with body weight of ≤ 120 kg.
6. N-terminal pro B-type natriuretic peptide level ≥ 125 pg/ml and < 8000 pg/ml at screening.
7. Patient with STEMI/NSTEMI who underwent percutaneous coronary intervention for this event.

Exclusion Criteria:

1. A woman of childbearing potential (WOCBP).
2. Patient with HF of non-ischemic origin; e.g., myocarditis, alcoholic cardiomyopathy.
3. Patient with New York Heart Association (NYHA) class IV at screening or randomization.
4. Patient has any planned cardiac intervention (angiogram without angioplasty is acceptable) or any other planned surgery after the Screening Period.
5. Patient has severe valvular heart disease.
6. Patient has systolic BP < 90 mmHg or > 180 mmHg, diastolic BP < 50 mmHg or > 110 mmHg, and/or heart rate < 50 or > 100 beats/minute at screening or randomization.
7. Patient with an estimated glomerular filtration rate < 30 mL/min/1.73 m2 or on dialysis.
8. Patient with hepatic insufficiency classified as Child-Pugh B or C.
9. Patient has medical history of disease(s) affecting the blood-brain-barrier, e.g., stroke within 6 months or multiple sclerosis.
10. Patient has medical history of bleeding disorders or has thrombocytopenia (platelets < 100,000/μL).
11. Patient has poorly controlled diabetes as determined by the Investigator.
12. Patient has a history or presence of any of the following cardiac conditions: known structural cardiac abnormalities beyond HF, family history of long QT syndrome, cardiac syncope, or recurrent, idiopathic syncope.
13. Any clinically significant abnormalities, at the discretion of the Investigator, in rhythm, conduction, or morphology of resting ECG that pose an additional safety risk to patients.
14. Patient with active "severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)" infection confirmed as per the local testing guidelines at screening.
15. Patient is not to be enrolled into the study if they received any prohibited therapy within 3 months of screening.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CDR132L 5 mg; CDR132L 5 mg/kg body weight intravenous in single dose on Day 1, Day 29 and Day 57	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.
Experimental: CDR132L 10 mg; CDR132L 10 mg/kg body weight intravenous in single dose on Day 1, Day 29 and Day 57	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; Placebo intravenous in single dose on Day 1, Day 29 and Day 57	Drug: Placebo to CDR132L; Placebo to CDR132L

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Echocardiography (ECHO)	Percent change from baseline (screening to occur at least 3 days after MI diagnosis as measured by ECHO [central laboratory]) in Left Ventricular End-Systolic Volume (LVESVI) at Month 6.	6 months

Collaborators and Investigators

• Sponsor: Cardior Pharmaceuticals GmbH
• Investigators: Principal Investigator: Johann Bauersachs, Prof. Dr., Hannover Medical School

Study record dates

Study Major Dates

• Study Start (Actual): June 27, 2022
• Primary Completion (Estimated): September 4, 2024
• Study Completion (Estimated): March 11, 2025

Study Registration Dates

• First Submitted: April 20, 2022
• First Submitted That Met QC Criteria: April 27, 2022
• First Posted (Actual): April 28, 2022

Study Record Updates

• Last Update Posted (Actual): March 19, 2024
• Last Update Submitted That Met QC Criteria: March 18, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; Heart Failure
• Other Study ID Numbers: CDR132L-P2-01; 2021-006040-27 (EudraCT Number)

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