Study to Assess Efficacy and Safety of CDR132L in Patients With Reduced Left Ventricular Ejection Fraction After Myocardial Infarction

NCT ID: NCT05350969

Last Updated: 2025-07-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 294 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-07-07
• Study Completion Date: 2025-03-17

Brief Summary

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.

Conditions

Myocardial Infarction, Acute; Heart Failure, Left Sided

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

CDR132L 5 mg

CDR132L 5 mg/kg body weight intravenous in single dose on Day 1, Day 29 and Day 57

Group Type: EXPERIMENTAL

CDR132L

Intervention Type: 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 10 mg

CDR132L 10 mg/kg body weight intravenous in single dose on Day 1, Day 29 and Day 57

Group Type: EXPERIMENTAL

CDR132L

Intervention Type: 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.

Placebo

Placebo intravenous in single dose on Day 1, Day 29 and Day 57

Group Type: PLACEBO_COMPARATOR

Placebo to CDR132L

Intervention Type: DRUG

Placebo to CDR132L

Interventions

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.

Intervention Type: DRUG

Placebo to CDR132L

Placebo to CDR132L

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cardior Pharmaceuticals GmbH

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Johann Bauersachs, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

Hannover Medical School

Locations

Institut klinicke a experimentalni mediciny

Prague, , Czechia

Všeobecná fakultní nemocnice v Praze

Prague, , Czechia

St. Marien-Krankenhaus Ahaus

Ahaus, , Germany

Herzzentrum Dresden Universitätsklinik

Dresden, , Germany

Helios Klinikum Erfurt

Erfurt, , Germany

Universitätsmedizin Göttingen

Göttingen, , Germany

Medizinische Hochschule Hannover

Hanover, , Germany

Universitätsklinikum Schleswig-Holstein

Kiel, , Germany

Klinikum Ludwigshafen

Ludwigshafen, , Germany

Universitätsklinikum Würzburg

Würzburg, , Germany

"Alexandra" General Hospital of Athens

Athens, , Greece

"Attikon" General University Hospital

Athens, , Greece

General University Hospital of Patras "Panagia i Voitheia"

Pátrai, , Greece

Semmelweis University

Budapest, , Hungary

Jeroen Bosch Ziekenhuis (JBZ) (Hieronymus Bosch Hospital) - locatie Den Bosch

's-Hertogenbosch, , Netherlands

Deventer Ziekenhuis

Deventer, , Netherlands

Slingeland Ziekenhuis

Doetinchem, , Netherlands

Gelderse Vallei Ziekenhuis

Ede, , Netherlands

Medisch Centrum Leeuwarden

Leeuwarden, , Netherlands

St. Jansdal Ziekenhuis

Lelystad, , Netherlands

Erasmus University Medical Center

Rotterdam, , Netherlands

Ikazia Ziekenhuis

Rotterdam, , Netherlands

D & A Research B.V.

Sneek, , Netherlands

Gelre Ziekenhuizen

Zutphen, , Netherlands

Polsko Amerykanskie Kliniki Serca

Kędzierzyn-Koźle, , Poland

Specjalistyczna Poradnia Kardiologiczna i Nadcisnienia Tetniczego

Kielce, , Poland

Krakowski Szpital Specjalistyczny im. Jana Pawla II

Krakow, , Poland

Gabinet Internistyczno-Kardiologiczny Jacek Nowak

Libiąż, , Poland

NZOZ SALUS JZ Peruga

Lodz, , Poland

One wojskowy Szpital Kliniczny w Lublinie

Lublin, , Poland

Medicome Sp. z o.o.

Oświęcim, , Poland

Wojewódzki Szpital im. Sw. Ojca Pio w Przemyslu

Przemyśl, , Poland

NZOZ Pro-Cordis Sopockie Centrum Bad. Kardiolog

Sopot, , Poland

Wojewodzki Szpital Zespolony

Torun, , Poland

Spec.Szpital im.dr Sokolowskiego

Wałbrzych, , Poland

Investigational Site

Wroclaw, , Poland

Hospital Universitari Germans Trias i Pujol

Badalona, , Spain

Hospital de la Santa Creu I Sant Pau

Barcelona, , Spain

Hospital Universitario San Cecilio

Granada, , Spain

Hospital Universitario La Paz

Madrid, , Spain

Hospital Universitario Virgen de la Arrixaca

Murcia, , Spain

Hospital Universitario de Sabadell

Sabadell, , Spain

Hospital Universitario Virgen Macarena

Seville, , Spain

Hospital Clinico Universitario de Valencia

Valencia, , Spain

Complejo Hospitalario Universitario de Vigo

Vigo, , Spain

Queen Elizabeth University Hospital

Glasgow, , United Kingdom

Wycombe Hospital

High Wycombe, , United Kingdom

Richmond Pharmacology Limited

London, , United Kingdom

South Tees Hospital NHS Foundation Trust

Middlesbrough, , United Kingdom

Countries

Czechia; Germany; Greece; Hungary; Netherlands; Poland; Spain; United Kingdom

Other Identifiers

2023-507569-24-00

Identifier Type: CTIS

Identifier Source: secondary_id

2021-006040-27

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CDR132L-P2-01

Identifier Type: -

Identifier Source: org_study_id