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

Myocardial Infarction, Acute Clinical Trial

— HF-REVERT  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05350969
• Other study ID #: CDR132L-P2-01
• Secondary ID: 2021-006040-27
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: June 27, 2022
• Est. completion date: March 11, 2025

Study information

• Verified date: March 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, 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 294
• Est. completion date: March 11, 2025
• Est. primary completion date: September 4, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Heart Failure
• Heart Failure, Left Sided
• Infarction
• Myocardial Infarction
• Myocardial Infarction, Acute

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 to CDR132L
Placebo to CDR132L

Locations

Country	Name	City	State
Czechia	Institut klinicke a experimentalni mediciny	Praha
Czechia	Všeobecná fakultní nemocnice v Praze	Praha
Germany	St. Marien-Krankenhaus Ahaus	Ahaus
Germany	Herzzentrum Dresden Universitätsklinik	Dresden
Germany	Helios Klinikum Erfurt	Erfurt
Germany	Universitätsmedizin Göttingen	Göttingen
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Universitätsklinikum Schleswig-Holstein	Kiel
Germany	Klinikum Leverkusen GmbH	Leverkusen
Germany	Klinikum Ludwigshafen	Ludwigshafen
Germany	Universitätsklinikum Würzburg	Würzburg
Greece	"Attikon" General University Hospital	Athen
Greece	"Alexandra" General Hospital of Athens	Athens
Greece	General University Hospital of Patras "Panagia i Voitheia"	Patra
Hungary	Semmelweis University	Budapest
Hungary	BMKK Pándy Kálmán	Gyula
Hungary	BKS Research Ltd.	Hatvan
Hungary	Somogy County Kaposi Mór Teaching Hospital	Kaposvár
Hungary	Medifarma-98 KFT	Nyíregyháza
Netherlands	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
Poland	Polsko Amerykanskie Kliniki Serca	Kedzierzyn-Kozle
Poland	Specjalistyczna Poradnia Kardiologiczna i Nadcisnienia Tetniczego	Kielce
Poland	Krakowski Szpital Specjalistyczny im. Jana Pawla II	Kraków
Poland	Gabinet Internistyczno-Kardiologiczny Jacek Nowak	Libiaz
Poland	NZOZ SALUS JZ Peruga	Lódz
Poland	One wojskowy Szpital Kliniczny w Lublinie	Lublin
Poland	Medicome Sp. z o.o.	Oswiecim
Poland	Wojewódzki Szpital im. Sw. Ojca Pio w Przemyslu	Przemysl
Poland	NZOZ Pro-Cordis Sopockie Centrum Bad. Kardiolog	Sopot
Poland	Wojewodzki Szpital Zespolony	Torun
Poland	Spec.Szpital im.dr Sokolowskiego	Walbrzych
Poland	Investigational Site	Wroclaw
Spain	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	Sevilla
Spain	Hospital Clinico Universitario de Valencia	Valencia
Spain	Complejo Hospitalario Universitario de Vigo	Vigo
United Kingdom	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

Sponsors (1)

Lead Sponsor	Collaborator
Cardior Pharmaceuticals GmbH

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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