Phase 2 Study to Assess Efficacy and Safety of CDR132L in Patients with Reduced Left Ventricular Ejection Fraction (≤45%) After Myocardial Infarction (HF-REVERT)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Cardior Pharmaceuticals GmbH

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

20 Jun 2022 → 18 Mar 2025

Decision date (initial)

2024-11-01

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Cardior Pharmaceuticals GmbH

External identifiers

EU CT number

2023-507569-24-00

EudraCT number

2021-006040-27

ClinicalTrials.gov

NCT05350969

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

To assess the efficacy of 2 dose levels (5 and 10 mg/kg) of CDR132L compared with placebo administered in 3 single IV doses given 28-days apart in patients with reduced LVEF ≤ 45% after MI (STEMI or NSTEMI) as add-on therapy to SoC treatment

Secondary objectives 7

1. To assess the safety of 2 dose levels (5 and 10 mg/kg) of CDR132L compared with placebo
2. To assess the effects of CDR132L compared with placebo on cardiac function
3. To assess the effects of CDR132L compared with placebo on efficacy-related biomarkers
4. To assess the effects of CDR132L compared with placebo on patient well-being
5. To determine the effects of CDR132L compared with placebo on HF episodes
6. To determine the effects of CDR132L compared with placebo on cardiac parameters
7. To determine the effect of CDR132L compared with placebo on exploratory biomarkers and immunogenicity

Conditions and MedDRA coding

Myocardial Infarction, Acute Heart Failure, Left Sided

Study design 1 period

Regulatory references

Scientific advice from competent authorities

Medicines Evaluation Board

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

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 15

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 and clinical relevant "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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Percent change from baseline (screening to occur at least 3 days (up to 14 days) after MI diagnosis as measured by ECHO [central laboratory]) in LVESVI at Month 6

Secondary endpoints 9

1. Frequency of adverse events and abnormalities in clinical laboratory assessments, vital signs, physical examination, ECGs, and urinalysis
2. Change from baseline LVEF (absolute/relative) at Months 3, 6, and 12
3. Change from baseline LVESVI at Month 3 (absolute/relative), Month 6 (absolute), and Month 12 (absolute/relative)
4. Change from baseline in absolute/relative troponin T (ng/L) at Months 3, 6, and 12
5. Change from baseline in absolute/relative values over time for the following efficacy-related biomarkers: N-terminal pro B-type natriuretic peptide (NT-proBNP)
6. Well-being as evaluated by change from baseline at Months 6 and 12 in the following parameters: Mean KCCQ score and mean scores of subdomains (symptom burden, physical limitation, and quality of life)
7. Heart failure as assessed by time to first event: Cardiovascular mortality; Hospitalization or emergency department visit(s) for HF conditions.
8. Change from baseline in the following parameters at Months 3, 6, and 12: NYHA class; ECHO: Left ventricular end-diastolic volume (mL), early (E) and late (A) diastolic transmitral flow velocity, early diastolic mitral annular velocity (e'), left atrial volume index, stroke volume (mL), systolic ejection time (ms), and strain analysis for global longitudinal strain; ECG: QRS complex, ECG interpretation
9. Levels of exploratory biomarkers (e.g., MicroRNA-132 [miR-132] for target engagement, LIPCAR, NGAL, Gal-3, PRO-C6, cardiac fibrosis markers) and immunogenic parameters (e.g., anti-drug antibodies) over time.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Cardior Pharmaceuticals GmbH

Sponsor organisation

Cardior Pharmaceuticals GmbH

Address

Hollerithallee 20, Marienwerder Marienwerder

City

Hanover

Postcode

30419

Country

Germany

Scientific contact point

Organisation

Cardior Pharmaceuticals GmbH

Contact name

Prof. Dr. Dr. Thomas Thum

Public contact point

Organisation

Cardior Pharmaceuticals GmbH

Contact name

Clinical Team

Third parties 8

Locations

7 EU/EEA countries · 50 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 40 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications