Clinical Trials Register

Summary
EudraCT Number:	2015-001381-26
Sponsor's Protocol Code Number:	CER-001-CLIN-010
National Competent Authority:	Hungary - National Institute of Pharmacy
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2015-05-12
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Hungary - National Institute of Pharmacy

A.2

EudraCT number

2015-001381-26

A.3

Full title of the trial

A PHASE II MULTI-CENTER, DOUBLE-BLIND, PLACEBO-CONTROLLED, DOSE-FOCUSING TRIAL OF CER-001 IN SUBJECTS WITH ACUTE CORONARY SYNDROME

II-ES FÁZISÚ, MULTICENTRIKUS, KETTŐS VAK, PLACEBO-KONTROLLÁLT, DÓZISFÓKUSZÁLÓ VIZSGÁLAT CER-001 VAGY PLACEBO HASZNÁLATÁVAL AKUT KORONÁRIA SZINDRÓMÁS BETEGEKBEN

A.3.1

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

A PHASE II MULTI-CENTER, DOUBLE-BLIND, PLACEBO-CONTROLLED, DOSE-FOCUSING TRIAL OF CER-001 IN SUBJECTS WITH ACUTE CORONARY SYNDROME

II-ES FÁZISÚ, MULTICENTRIKUS, KETTŐS VAK, PLACEBO-KONTROLLÁLT, DÓZISFÓKUSZÁLÓ VIZSGÁLAT CER-001 VAGY PLACEBO HASZNÁLATÁVAL AKUT KORONÁRIA SZINDRÓMÁS BETEGEKBEN

A.3.2

Name or abbreviated title of the trial where available

CARAT - CER-001 ATHEROSCLEROSIS REGRESSION ACS TRIAL

A.4.1

Sponsor's protocol code number

CER-001-CLIN-010

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	CERENIS THERAPEUTICS SA
B.1.3.4	Country	France
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	CERENIS THERAPEUTICS SA
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	InterEuropa Clinical Research B.V.
B.5.2	Functional name of contact point	Clinical Research
B.5.3	Address:
B.5.3.1	Street Address	Mathenesserlaan 247
B.5.3.2	Town/ city	Rotterdam
B.5.3.3	Post code	3021 HC
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	+31103100660
B.5.6	E-mail	cecile.lardinois@intereuropa.org

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.3.1	Product name	Recombinant Human Apolipoprotein A-I/Phospholipids Complex
D.3.2	Product code	CER-001
D.3.4	Pharmaceutical form	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	ApoA-I
D.3.9.2	Current sponsor code	CER-001
D.3.9.3	Other descriptive name	recombinant human apolipoprotein A-I
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	8.0
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Sph
D.3.9.3	Other descriptive name	Sphingomyelin
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20.95
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	DPPG
D.3.9.3	Other descriptive name	1,2-Dihexadecanoyl-sn-Glycero-3-Phospho-(1-raac-glycerol)
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.65
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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

Acute Coronary Syndrome (ACS) with significant plaque volume

E.1.1.1

Medical condition in easily understood language

Acute Coronary Syndrome (ACS) with significant plaque volume

E.1.1.2

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

MedDRA Classification

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 impact of ten intravenous infusions of 3 mg/kg CER-001 vs. placebo, given at weekly intervals, on atherosclerotic plaque volume as measured by coronary IVUS, when administered to subjects presenting with Acute Coronary Syndrome (ACS) with significant plaque volume.

E.2.2

Secondary objectives of the trial

Secondary atherosclerosis efficacy parameters will include the (i) nominal change from baseline to follow-up in normalized total atheroma volume (TAV) and (ii) nominal change in TAV in the 10-mm sub segment of the coronary artery with the largest plaque volume at baseline (the most diseased segment).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Subjects must provide informed consent, as approved by the IRB/EC prior to performance of any screening procedures
2. Male or female at least 18 years of age
3. Subject of non child-bearing potential,
a) Greater than 12 months since last menstrual period; and/or surgically sterilized and agree to use barrier method of birth control for the entire study; and/or
b) On hormonal therapy (including implants, injections, combined oral contraceptives and IUDs) and agree to use a barrier method of birth control for the entire study: and/or
c) Agree to use a double barrier method of birth control defined as condom in combination with diaphragm, contraceptive sponge, spermicidal foam or cervical cap.
4. Subjects who undergo coronary angiography within 7 days of presentation with ACS:
ACS Criteria Myocardial Infarction
a) Cardiac biomarkers (troponin I or T, CKMB mass, or CK-MB activity) with at least one determination > 99th percentile or above the local laboratory upper reference limit
AND one of the following:
b) Chest pain or ischemic symptoms at rest >10 minutes within prior 24 hours
c) New ECG changes of acute ischemia (LBBB, ST elevations, or ST depressions)
d) New pathologic Q-waves or R/S >1 in V1- V2
e) Regional myocardial scar or ischemia by nuclear, magnetic resonance, echocardiographic, or angiographic imaging
OR Biomarker-Negative ACS (Unstable Angina)
a) No elevation of cardiac biomarkers
b) Chest pain or ischemic symptoms at rest >10 minutes
c) Prompting Hospitalization or chest pain observation unit within 24 hours of symptoms
AND one of the following:
d) New or worsening ECG changes (transient ST elevation, ST depression, or T inversion)
e) Definite myocardial ischemia on nuclear or echocardiographic imaging
f) Angiographic stenosis >70% or thrombus in epicardial coronary artery or bypass graft and/or performance of PCI
5. Baseline Coronary angiogram must meet all the following criteria for IVUS interrogation of Target Artery;
Target Artery:
a) Must be accessible to the IVUS catheter
b) Must have a stenotic area of ≤50% in lumen diameter by angiographic visual estimation within the length of the native coronary artery for imaging by IVUS
c) The target artery may not be a bypass graft
d) The target artery may not be the culprit vessel for a previous MI
Target Artery May Have:
a) A lesion up to 60% stenosis, distal to the target segment, provided that this area is not anticipated to be a target for PCI or CABG during the course of the study
b) A single branch of the target artery may have a narrowing ≤70% by visual estimation, provided that the branch is not a target for PCI or CABG during the course of the study
6. Subject is able to be randomized within 14 days of ACS event presentation
7. Baseline IVUS interrogation determined to be of acceptable quality with PAV ≥ 30% in the proximal 10mm at review by the Imaging Core Lab
8. Subject must be willing to participate in the study and comply with all protocol requirements, including willingness to:
a) Return to the clinic weekly for a total of ten IV infusions of study drug
b) Return to the clinic for follow up visits
c) Return to the clinic at the end of the study for follow up IVUS procedure

E.4

Principal exclusion criteria

1. Baseline IVUS not completed due to non-qualifying coronary angiogram as demonstrated by:
a) Greater than 50% reduction in lumen of the left main coronary artery by visual estimation
b) Extensive coronary artery disease with no target vessel for IVUS interrogation
c) Angiographically normal coronary arteries
2. Baseline IVUS interrogation determined to be unacceptable by the Imaging Core Lab
3. Subjects with uncontrolled diabetes defined as HbA1c > 10% at Screening
4. Subjects with triglycerides >500 mg/dL at Screening
5. Subjects with coronary artery bypass graft (CABG) surgery in previous 6 weeks or in whom CABG is planned
6. Myocardial infarction in the target coronary artery for IVUS between the initial IVUS examination and randomization
7. Subjects who have symptomatic congestive heart failure (CHF) (New York Heart Association [NYHA] Class III or IV) at baseline
8. Subjects with a known ejection fraction <35% (investigations to document EF not required)
9. Subjects with clinically significant valvular heart disease likely to require surgical repair or replacement during the treatment period of the study
10. Subject is hemodynamically or clinically unstable in the opinion of the Investigator.
11. Subject has uncontrolled hypertension (e.g., sitting systolic BP > 180 mm Hg on antihypertensive therapy) at time of randomization
12. Subject has known major hematologic, hepatic (liver enzymes greater than twice the upper limits of normal for the performing laboratory), metabolic, gastrointestinal or endocrine dysfunction in the judgment of the Investigator
13. Subject has known renal dysfunction CrCl = ≤30mL/min
14. Any clinically significant medical condition or presence of any laboratory abnormality performed prior to randomization that is considered by the investigator to be clinically important and could interfere with the conduct of the study
15. Subject is likely to be unreliable as a study participant based on the Investigator's (or designee’s) knowledge of the subject (e.g., alcohol or other drug abuse, inability or unwillingness to adhere to the protocol, or psychosis)
16. Subject has participated in any investigational drug or interventional device study within 30 days prior to randomization, or expects to participate in any other investigational drug or interventional device study during his/her planned participation in this study
17. Subject has previously participated in this study or another study involving CER-001.

E.5 End points

E.5.1

Primary end point(s)

Primary endpoint: comparison of the primary efficacy parameter between randomized treatment groups (Placebo vs. CER-001 3 mg/kg) using an analysis of covariance (ANCOVA) with adjustment for baseline PAV.
Adjusted mean endpoint in each treatment group and the difference in means (95% confidence interval) will be presented.
Statistical significance will be assessed at the alpha=0.05 level.

E.5.1.1

Timepoint(s) of evaluation of this end point

Baseline 1st infusion, end of study

E.5.2

Secondary end point(s)

Secondary atherosclerosis efficacy parameters will include the (i) nominal change from baseline to follow-up in normalized Total Atheroma Volume (TAV) and (ii) nominal change in TAV in the 10-mm sub segment of the coronary artery with the largest plaque volume at baseline (the most diseased segment).

E.5.2.1

Timepoint(s) of evaluation of this end point

Baseline 1st infusion, end of study

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

Yes

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

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

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Australia

United States

E.8.7

Trial has a data monitoring committee

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

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:

234

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

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

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

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

146

F.4.2.2

In the whole clinical trial

292

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)

Regular care

G. Investigator Networks to be involved in the Trial

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2015-07-22

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-06-23

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2016-11-30

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials