ICH GCP - EU Clinical trials Registry - 2012-000856-33 (FR)

Prove cliniche Nct

Summary
EudraCT Number:	2012-000856-33
Sponsor's Protocol Code Number:	2012-40
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2014-05-15
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

A. Protocol Information

A.1

Member State Concerned

France - ANSM

A.2

EudraCT number

2012-000856-33

A.3

Full title of the trial

A phase I/II, open-label, study of intracerebral administration of adeno-associated viral vector containing the human alpha-N-acetylglucosaminidase cDNA in children with Sanfilippo type B syndrome

A.3.1

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

Intracerebral Gene therapy in children with Sanfilippo type B syndrome

A.4.1

Sponsor's protocol code number

2012-40

A.5.1

ISRCTN (International Standard Randomised Controlled Trial) Number

ISRCTN19853672

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	Institut Pasteur
B.1.3.4	Country	France
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Association Française contre les Myopathies
B.4.2	Country	France
B.4.1	Name of organisation providing support	Institut Pasteur
B.4.2	Country	France
B.4.1	Name of organisation providing support	Vaincre les Maladies Lysosomales
B.4.2	Country	France
B.4.1	Name of organisation providing support	Astellas
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	Institut Pasteur
B.5.2	Functional name of contact point	PIRC
B.5.3	Address:
B.5.3.1	Street Address	25-28 rue du Dr Roux
B.5.3.2	Town/ city	Paris
B.5.3.3	Post code	75015
B.5.3.4	Country	France
B.5.4	Telephone number	+33144389101
B.5.5	Fax number	+33140613977
B.5.6	E-mail	ecsanfilippo@pasteur.fr

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/3/11/917
D.3 Description of the IMP
D.3.1	Product name	rAAV2/5-hNaGlu
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	Yes
D.3.7	Routes of administration for this IMP	Intracerebral use
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)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	Yes
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	Yes
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	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	Yes
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Mucopolysaccharidosis III B

E.1.1.1

Medical condition in easily understood language

sanfilippo B syndrome

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	17.0
E.1.2	Level	PT
E.1.2	Classification code	10056890
E.1.2	Term	Mucopolysaccharidosis III
E.1.2	System Organ Class	10010331 - Congenital, familial and genetic disorders

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 clinical, radiological, biological tolerance associated to the proposed treatment

E.2.2

Secondary objectives of the trial

To collect samples and data to define exploratory tests that could become evaluation criteria and further clinical efficacy studies (Brain MRI; neurological tests and biological markers)

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Age: 18 months up to the 5th birthday;
Onset of clinical manifestations related to MPSIIIB;
NaGlu activity in peripheral blood cell and/or cultured fibroblast extracts of less than 10% of controls;
Patient affiliated to, or covered by a French social security regimen or European patients with European Health Insurance Card
Family understanding the procedure and the informed consent;
Signed informed consent by both parents or legal representative
Vital laboratory parameters within normal range

E.4

Principal exclusion criteria

Presence of brain atrophy on pre-inclusion MRI judged on a cortico-dural distance of more than 0.6 cm
Any condition that would contraindicate general anaesthesia;
Any other permanent medical condition not related to MPSIIIB that could contraindicate the study participation;
No independent walking (Ability to walk without help);
Any medication aiming at modifying the natural course of MPSIIIB given during the 6 months before vector injection (sleep and mood regulators are accepted)
Any condition that would contraindicate treatment with Tacrolimus, Cellcept® and Solupred®/Solumedrol®.

E.5 End points

E.5.1

Primary end point(s)

Occurrence, intensity and relationship of all TEAEs. It will be presented overall by Prefered Term and System Organ Class (SOC).
Occurrence, intensity and relationship of TEAEs per periods: 15 days post-surgery and during the 1 year follow-up in order to discriminate short- and mid-term safety.
Occurrence and relationship of all TESAEs occurring during the study period.
Occurrence, intensity and relationship of clinically significant abnormal haematology or biochemistry values (grade 3 or 4) occurring from immunosuppressant regimen start to the end of the study participation.

E.5.1.1

Timepoint(s) of evaluation of this end point

1year

E.5.2

Secondary end point(s)

Endpoints related to the secondary objective of the protocol will show the accuracy of the data and samples collection and the ability of the children to be evaluated by the different neuropsychological tests that have been chosen.

E.5.2.1

Timepoint(s) of evaluation of this end point

1year

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

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)

Yes

E.7.1.1

First administration to humans

Yes

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

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

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)

Information not present in EudraCT

E.8.2.2

Placebo

Information not present in EudraCT

E.8.2.3

Other

Information not present in EudraCT

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

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

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1

Number of subjects for this age range:

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)

Yes

F.1.1.4.1

Number of subjects for this age range:

F.1.1.5

Children (2-11years)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

F.1.3

Elderly (>=65 years)

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

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

patients are under 5 years old at inclusion. Sanfilippo type B disease induces severe mental deficiency when growing-up.

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

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)

An extension study will be proposed for the long term safety evaluation of the proposed treatment. Immunosuppressant treatment under tacrolimus will be extended. The initial duration of the extension phase will be of one year and will be repeated each year. Parents will sign a new informed consent before each extension phase.

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

2013-09-09

Ethics Committee Opinion of the trial application

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2019-11-27

Prove cliniche Nct

Sponsor e collaboratori

Condizioni mediche

Interventi farmacologici