Clinical Trials Register

Summary
EudraCT Number:	2021-006040-27
Sponsor's Protocol Code Number:	CDR132L-P2-01
National Competent Authority:	Poland - Office for Medicinal Products
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2022-09-29
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Poland - Office for Medicinal Products

A.2

EudraCT number

2021-006040-27

A.3

Full title of the trial

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 (HF-REVERT)

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

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

A.3.2

Name or abbreviated title of the trial where available

HF-REVERT

A.4.1

Sponsor's protocol code number

CDR132L-P2-01

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Cardior Pharmaceuticals GmbH
B.1.3.4	Country	Germany
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Cardior Pharmaceuticals GmbH
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Cardior Pharmaceuticals GmbH
B.5.2	Functional name of contact point	Clinical Department
B.5.3	Address:
B.5.3.1	Street Address	Hollerithallee 20,
B.5.3.2	Town/ city	Hannover
B.5.3.3	Post code	30419
B.5.3.4	Country	Germany
B.5.4	Telephone number	004951133 85 99 30
B.5.5	Fax number	004951133 85 99 39
B.5.6	E-mail	clinical@cardior.de

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.2	Product code	CDR132L
D.3.4	Pharmaceutical form	Powder for concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Not yet defined
D.3.9.2	Current sponsor code	CDR132L
D.3.9.3	Other descriptive name	CDR132L
D.3.9.4	EV Substance Code	SUB258482
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for infusion
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Reduced Left Ventricular Ejection Fraction After Myocardial Infarction

E.1.1.1

Medical condition in easily understood language

Heart Failure after Myocardial Infarction

E.1.1.2

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10036233
E.1.2	Term	Post myocardial infarction syndrome
E.1.2	System Organ Class	10007541 - Cardiac disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

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

E.2.2

Secondary objectives of the trial

•To assess the safety of 2 dose levels (5 and 10 mg/kg) of CDR132L compared with placebo
•To assess the effects of CDR132L compared with placebo on cardiac function
•To assess the effects of CDR132L compared with placebo on efficacy related biomarkers
•To assess the effects of CDR132L compared with placebo on patient well being

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male or female of non-childbearing potential 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 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 NSTEMI with evidence of significant myocardial necrosis, evidenced through a troponin T or troponin I increase to at least 5 times the upper limit of normal (ULN) at MI index event diagnosis.
5. Patient with previous MI events in history can be included.
6. A male patient must agree to use contraception as detailed in Appendix 5 of this protocol during the treatment period and for at least 30 days after the last dose of study treatment and refrain from donating sperm during this period.
7. Patient with body weight of ≤ 120 kg.
8. N-terminal pro B-type natriuretic peptide level ≥ 125 pg/mL and < 8000 pg/mL.
Note: NT-proBNP values required for eligibility confirmation may be collected at any time post MI either through medical history (e.g., site has collected it as SoC once the patient came to the hospital), through a local laboratory assessment, or by sending a sample to the central laboratory.
9. Patient with STEMI/NSTEMI who underwent percutaneous coronary intervention or angiography (if no indication for stent placement or balloon procedure) for this event.
10. Capable of giving signed informed consent as described in Appendix 2 of the protocol, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

E.4

Principal exclusion criteria

1.A woman of childbearing potential (WOCBP) as defined in Appendix 5.
2.Patient with HF of non-ischemic origin; e.g., myocarditis, alcoholic cardiomyopathy.
3.Patient with history of decompensated HF or a history of LVEF < 30% within 6 months prior to MI index event.
4.Patient with NYHA class IV at screening or randomization.
5.Patient has any planned cardiac intervention (angiogram without angioplasty is acceptable) or any other planned surgery after the Screening Period.
6.Patient has severe valvular heart disease.
7.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.
8.Patient with an estimated glomerular filtration rate < 30 mL/min/1.73 m2 or on dialysis.
9.Patient with hepatic insufficiency classified as Child Pugh B or C.
10.Patient with known active human immunodeficiency virus, Hepatitis B, or Hepatitis C infection at screening.
11.Impaired hepatic function defined by a total bilirubin level of ≥ 2 × the ULN and ALT levels of ≥ 3 × ULN.
12.Patient has medical history of disease(s) affecting the blood-brain-barrier, e.g., stroke within 6 months or multiple sclerosis.
13.Patient has medical history of bleeding disorders or has thrombocytopenia (platelets < 100,000/µL).
14.Patient has poorly controlled diabetes as determined by the Investigator.
15.Patient is currently on treatment for epilepsy.
16.Patient has a current or relevant history of physical or psychiatric illness that is/are not stable or may require a change in treatment, use of prohibited therapies during the study, or cause the patient to be unlikely to fully comply with the requirements of the study or complete the study, or any condition that presents undue risk from the study drug or study procedures.
17.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.
18.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. This will include patients with any of the following (at Screening Visit or Day -1):
a)Clinically significant PR (PQ) interval prolongation.
b)Intermittent second- or third degree atrioventricular block.
c)Sustained cardiac arrhythmia including (but not limited to) supraventricular tachycardia, any symptomatic arrhythmia with the exception of isolated extra systoles.
19.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.
20.Patient has other significant disease or disorder which, in the opinion of the Investigator, may put the patient at risk because of participation in the study or may influence the result of the study or the patient's ability to participate in the study.
21.Patient has received an investigational product or treated with an investigational device within 90 days prior to first study drug administration.
22.Patient has known or suspected intolerance or hypersensitivity to the study drug, any closely related compound, or any of the stated ingredients.
23.Patient is not to be enrolled into the study if they received any prohibited therapy within 3 months before the first administration of study drug (please see also section 6.5.1):
a) Treatment with anticancer therapy (chemotherapy, immunotherapy, radiotherapy, targeted therapy, or gene therapy)
b) Administration of any other investigational agent
24.Patient is involved in the planning and/or conduct of the study (applies to Sponsor staff, staff at the study site, and third-party vendors).

E.5 End points

E.5.1

Primary end point(s)

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

E.5.1.1

Timepoint(s) of evaluation of this end point

6 months

E.5.2

Secondary end point(s)

Secondary Endpoint 1: Frequency of adverse events and abnormalities in clinical laboratory assessments, vital signs, physical examination, ECGs, and urinalysis
Secondary Endpoint 2: Change from baseline LVEF (absolute/relative) at Months 3, 6, and 12. Change from baseline LVESVI at Month 3 (absolute/relative), Month 6 (absolute), and Month 12 (absolute/relative)
Secondary Endpoint 3: Change from baseline in absolute/relative troponin T (ng/L) at Months 3, 6, and 12. Change from baseline in absolute/relative values over time for the following efficacy related biomarkers:
oN-terminal pro B-type natriuretic peptide (NT-proBNP)
Secondary Endpoint 4: • Well-being as evaluated by change from baseline at Months 6 and 12 in the following parameters:
oMean KCCQ score and mean scores of subdomains (symptom burden, physical limitation, and quality of life)

E.5.2.1

Timepoint(s) of evaluation of this end point

Secondary Endpoint 1: Through out the study
Secondary Endpoint 2: 3,6 and 12 months
Secondary Endpoint 3: 3,6 and 12 months
Secondary Endpoint 4: 6 and 12 months

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

140

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

140

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

280

F.4.2.2

In the whole clinical trial

280

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1
G.4.1	Name of Organisation	Werkgroep Cardiovasculaire centra Nederland
G.4.3.4	Network Country	Netherlands

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2022-12-09

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-05-26

P. End of Trial
P.	End of Trial Status	Ongoing

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