Clinical Trials Register

Summary
EudraCT Number:	2015-003713-23
Sponsor's Protocol Code Number:	CER-001-CLIN-009
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2015-09-28
Trial results	View 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

Netherlands - Competent Authority

A.2

EudraCT number

2015-003713-23

A.3

Full title of the trial

PHASE III, MULTI-CENTER, RANDOMIZED, 48 WEEKS, DOUBLE-BLIND, PARALLEL-GROUP, PLACEBO-CONTROLLED STUDY TO EVALUATE EFFICACY AND SAFETY OF CER-001 ON VESSEL WALL AREA IN PATIENTS WITH GENETICALLY DEFINED FAMILIAL PRIMARY HYPOALPHALIPOPROTEINEMIA AND RECEIVING BACKGROUND OPTIMIZED LIPID THERAPY, WITH OPTIONAL OPEN-LABEL SAFETY EXTENSION

A.3.1

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

PHASE III, MULTI-CENTER STUDY TO EVALUATE EFFICACY AND SAFETY OF 48 WEEKS CER-001 TREATMENT IN PATIENTS WITH GENETICALLY DEFINED FAMILIAL PRIMARY HYPOALPHALIPOPROTEINEMIA AND RECEIVING BACKGROUND OPTIMIZED LIPID THERAPY. CER-001 WILL BE COMPARED TO THE PLACEBO, AND NEITHER THE PATIENTS NOR THE DOCTORS WILL KNOW THE TREATMENT TAKEN BY THE PATIENTS. AN OPTIONAL CER-001 TREATMENT EXTENSION PERIOD WILL BE PROPOSED.

A.3.2

Name or abbreviated title of the trial where available

TANGO

A.4.1

Sponsor's protocol code number

CER-001-CLIN-009

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	Clinical Trial Service B.V.
B.5.2	Functional name of contact point	Ms. D. Ekkel
B.5.3	Address:
B.5.3.1	Street Address	Gronausestraat 98
B.5.3.2	Town/ city	Losser
B.5.3.3	Post code	7581 CJ
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	0031535362220
B.5.5	Fax number	0031535382022
B.5.6	E-mail	dianne.ekkel@clinicaltrialservice.com

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	Yes
D.2.5.1	Orphan drug designation number	EU/3/14/1314 (ABCA1) EU/3/14/1315 (ApoA-1)
D.3 Description of the IMP
D.3.1	Product name	Recombinant Human Apolipoprotein A-1/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/kg milligram(s)/kilogram
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

GENETICALLY DEFINED FAMILIAL PRIMARY HYPOALPHALIPOPROTEINEMIA (FPHA mutation in ApoA1 and/or ABCA1 gene)

E.1.1.1

Medical condition in easily understood language

Very low HDL-C level and either mutations in your ApoA-I or/and ABCA1 gene

E.1.1.2

Therapeutic area

Body processes [G] - Genetic Phenomena [G05]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	19.1
E.1.2	Level	LLT
E.1.2	Classification code	10019185
E.1.2	Term	HDL cholesterol decreased
E.1.2	System Organ Class	100000004848

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate the effect of 24 weeks treatment with CER-001 on carotid Mean Vessel Wall Area (MVWA) as compared to placebo using 3T magnetic resonance imaging (3T-MRI);
To evaluate the safety and tolerability of CER-001 administered for 24 weeks

E.2.2

Secondary objectives of the trial

To evaluate the effect of 8 weeks and 48 weeks treatment with CER-001 on MVWA as compared to placebo using 3T-MRI;
To evaluate the effect of 8 weeks, 24 weeks and 48 weeks treatment with CER-001 on femoral artery as compared to placebo using 3T-MRI;
To evaluate the effect of 24 weeks treatment with CER-001 in the target (plaque) to background (blood) ratio (TBR) from an index vessel (either right carotid, left carotid) based on the standardized 18FDG uptake measured with PET/CT;
To evaluate safety and tolerability of CER-001 administered for 48 weeks

Other objectives:
To evaluate safety and tolerability of 72 week treatment with CER-001.
To evaluate the effect of 72 week treatment with CER-001 on MVWA using 3T-MRI;
To evaluate the effect of 72 week treatment with CER-001 on femoral artery using 3T-MRI;

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male and female patients, aged 18 and above.
2. Female patients who are not either surgically sterile (e.g., tubal ligation or removal of ovaries or uterus) or post-menopausal (no spontaneous menstrual periods for at least one year) must agree to use one of the following forms of contraception from screening until 90 days after the completion of the study medication: (1) systemic hormonal treatment (2) an IUD which was implanted at least 2 months prior to screening or (3) "double-barrier" contraception (condom, diaphragm and spermicide are each considered a barrier), or (4) agree to remain sexually abstinent during the entire study period (when contraception is not acceptable for cultural or religious beliefs)
3. Sign written informed consent after the scope and nature of the investigation have been explained to them before screening evaluations and willing to comply with the study restrictions
4. Are fluent in the language of the investigator, study staff (including raters), and the informed consent
5. Diagnosis of genetically confirmed HDL-c deficiency due to defects in genes coding for e.g. ABCA1 and/or ApoA-1
6. IF the subject is on lipid-lowering therapy or NEEDS to be treated with lipid-lowering therapy then the subject must be on a stable dose at least 6 weeks prior to the baseline procedures.
7. Background symptomatic or asymptomatic cardiovascular disease should be present as such:
- For symptomatic cardiovascular disease: i) history of cardio or cerebrovascular events, ii) diagnosed coronary artery disease (CAD), iii) diagnosed carotid or peripheral stenosis, iv) previous myocardial revascularisation - percutaneous coronary intervention (PCI), or coronary artery bypass graft (CABG).
- For asymptomatic cardiovascular disease: patients with subclinical atherosclerosis diagnosed using imaging method such as i)vDoppler ultrasound, ii)vB-mode ultrasonography – measurement of carotid intima media thickness, iii)vintravascular ultrasonography, iv) Computed Tomography, v) Magnetic Resonance Imaging
8. ApoA-1 ≤ 110 mg/dL
9. HDL-cholesterol ≤ 35 mg/dL or 0.9 mmol/L

E.4

Principal exclusion criteria

EXCLUSION CRITERIA
Patients meeting any one of the following criteria are not eligible for the study:
1. Patient with LCAT mutation will be excluded
2. Patient who experienced a cardiovascular event within 6 months prior to the onset of screening
3. Patient who experienced stroke or other cerebrovascular event within 1 year prior to the onset of screening
4. Patients with triglycerides level above 500 mg/dL
5. The patient has evidence of clinically significant, uncontrolled or unstable cardiovascular, renal, hepatic (incl. AST or ALT at or above 3x ULN, or bilirubin at or above 2x ULN), gastrointestinal, hematologic, immunological, neurological, endocrine, metabolic or pulmonary disease (as determined by medical history, clinical laboratory or ECG results, or physical examination) or any other medical disorder that would increase the risk associated with taking study medication or would confound the interpretation of study results.
6. Patients with a body mass index (BMI) < 17 kg/m2 or > 40 kg/m2
7. Patients with severe anemia defined as hemoglobin level below or equal to 10 g/dL
8. Any clinically significant abnormal laboratory data, vital signs, physical examination at screening or baseline, which in the opinion of the investigator, would interfere with safety assessments
9. Clinically significant ECG abnormality at screening, including sinus bradycardia (resting heart rate < 50 beats per minute), 2nd or 3rd degree atrioventricular block, prolonged QTc (QTcF ≥ 450 ms in males and ≥ 470 ms in females) history of congenital long QT syndromes, or risk of Torsades de Pointes because of family history of sudden death, etc.
10. Positive result on the serum pregnancy test or are breast feeding at screening, or intend to become pregnant during the course of the trial
11. Male intending to get a child during the study
12. Likely to be unreliable as a study participant based on the Investigator's (or designee’s) knowledge of the patient (e.g., alcohol or other drug abuse, inability or unwillingness to adhere to the protocol, or psychosis)
13. Symptomatic (NYHA Class II or greater) congestive heart failure requiring and persisting despite appropriate medical treatment
14. Uncontrolled blood pressure: systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg at screening or any other pre-randomization visit
15. Uncontrolled diabetes mellitus defined as HbA1c >10%
16. Unexplained creatine phosphokinase level > 3 times the ULN
17. History of malignancy during the 3 years prior to screening, with the exception of basal cell carcinoma of the skin
18. Current alcohol or drug abuse or history thereof within 5 years prior to screening
19. Contraindication to MRI scanning such as imbedded metal (e.g., schrapnel), implanted metal objects (e.g., pacemaker), claustrophobia.
20. Participated in any investigational study or taken an investigational drug within 30 days (or 5 times the half-life of the investigational drug, whatever is longer)
21. Ever received CER-001 within 6 months from the onset of screening
22. Medically non-compliant in the management of their disease in the investigator’s opinion

E.5 End points

E.5.1

Primary end point(s)

PRIMARY EFFICACY PARAMETER:
The primary efficacy parameter of this study will be the change from baseline after 24 weeks treatment with CER-001 on carotid Mean Vessel Wall Area (MVWA) as compared to placebo using 3T-MRI when administered to patients with genetically defined FPHA.

E.5.1.1

Timepoint(s) of evaluation of this end point

After 24 weeks treatment with CER-001

E.5.2

Secondary end point(s)

SECONDARY EFFICACY PARAMETERS:
• Change from baseline after 8 week and 48 week treatment with CER-001 on MVWA as compared to placebo using 3T-MRI when administered to patients with genetically defined FPHA.
• Change from baseline after 8, 24 and 48 week treatment with CER-001 on femoral artery as compared to placebo using 3T-MRI when administered to patients with genetically defined FPHA.
• Change from baseline at 24 weeks in the TBR from an index vessel (either right carotid or left carotid) based on the standardized 18FDG uptake measured with PET/CT in patients with genetically defined FPHA.
SECONDARY SAFETY PARAMETERS:
• Incidence and severity of AEs from routine monitoring.
• Incidence of abnormalities and changes from baseline in clinical laboratory parameters from testing of blood and urine, including anti-ApoA-1 antibody.
• Incidence of cardiovascular events.

OTHER EFFICACY PARAMETERS:
• Change from baseline after 72 week treatment with CER-001 on carotid Mean Vessel Wall Area (MVWA) using 3T-MRI when administered to patients with genetically defined FPHA
• Change from baseline after 72 week treatment with CER-001 on femoral artery using 3T-MRI when administered to patients with genetically defined FPHA

E.5.2.1

Timepoint(s) of evaluation of this end point

After 8, 24, 48 and 72 week treatment with CER-001

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

Yes

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)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

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

Yes

E.8.1.7.1

Other trial design description

Open-labeled treatment phase after 48 week double blind phase

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

Belgium

Canada

France

Israel

Italy

Netherlands

United States

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:

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

F.4.2.2

In the whole clinical trial

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)

The sponsor intends to prepare an open extension study protocol to include any patient depending on the outcome of TANGO study.

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

2015-09-28

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-11-11

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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