Clinical Trials Register

Summary
EudraCT Number:	2013-005528-40
Sponsor's Protocol Code Number:	EPISTOP
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2014-07-14
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

Netherlands - Competent Authority

A.2

EudraCT number

2013-005528-40

A.3

Full title of the trial

Long-term, prospective study evaluating clinical and molecular biomarkers of epileptogenesis in a genetic model of epilepsy – Tuberous Sclerosis Complex.

Een lange-termijn, prospectieve studie om klinische en moleculaire biomarkers van epileptogenese in kaart te brengen in een genetisch model voor epilepsie - Tubereuze Sclerosis Complex.

A.3.1

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

Long-term, prospective study evaluating clinical and molecular biomarkers of epileptogenesis in a genetic model of epilepsy – Tuberous Sclerosis Complex.

Een lange-termijn, prospectieve studie om klinische en moleculaire biomarkers van epileptogenese in kaart te brengen bij patiënten met Tubereuze Sclerosis Complex.

A.3.2

Name or abbreviated title of the trial where available

EPISTOP

A.4.1

Sponsor's protocol code number

EPISTOP

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT02098759

A.5.4

Other Identifiers

Name:

Dutch ABR form

Number:

48101

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	The Children's Memorial Health Institute
B.1.3.4	Country	Poland
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	European Commission
B.4.2	Country	European Union
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	The Children's Memorial Health Institute
B.5.2	Functional name of contact point	EPISTOP Project Office
B.5.3	Address:
B.5.3.1	Street Address	Al. Dzieci Polskich 20
B.5.3.2	Town/ city	Warsaw
B.5.3.3	Post code	04-730
B.5.3.4	Country	Poland
B.5.4	Telephone number	0048228157854
B.5.6	E-mail	epistop@ipczd.pl

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	Yes
D.2.1.1.1	Trade name	Vigabatrin (Sabril)
D.2.1.1.2	Name of the Marketing Authorisation holder	Sanofi-Aventis Netherlands B.V.
D.2.1.2	Country which granted the Marketing Authorisation	Netherlands
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	vigabatrin
D.3.4	Pharmaceutical form	Granules in sachet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Epilepsy in tuberous sclerosis complex (TSC)

Epilepsie bij Tubereuze Sclerosis Complex (TSC)

E.1.1.1

Medical condition in easily understood language

Epilepsy in tuberous sclerosis complex (TSC)

Epilepsie bij Tubereuze Sclerosis Complex

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	17.0
E.1.2	Level	LLT
E.1.2	Classification code	10032061
E.1.2	Term	Other forms of epilepsy
E.1.2	System Organ Class	100000004852

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

The primary objective of clinical part of EPISTOP project is to identify the clinical and molecular biomarkers of epileptogenesis in a prospective clinical study of patients with TSC.

Het primaire doel van de EPISTOP trial is om klinische en moleculaire biomarkers van epileptogenese te identificeren, in een prospectieve klinische studie bij zuigelingen met TSC.

E.2.2

Secondary objectives of the trial

Secondary objective of the clinical part of EPISTOP is to compare the effects of standard antiepileptic treatment in patients diagnosed as having epilepsy after clinical seizures vs after electroencephalographic epileptiform discharges, in a randomized trial in TSC patients.

Het secundaire doel van de EPISTOP trial is om het effect van vroege behandeling - na het ontstaan van epileptiforme EEG afwijkingen - te vergelijken met het effect van standaard behandeling - na het ontstaan van klinische aanvallen -, in een randomized controlled trial.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Male or female infants with a definite diagnosis of TSC (Roach criteria; Roach 1998 or DNA confirmed),
- Age up to 4 months at the moment of enrolment,
- No clinical seizures seen by caregivers or on baseline videoEEG recording,
- Written informed consent of caregivers. It is possible to give consent for the observational part of the study only. In this case, the child will not enter the randomized part of the study.

- Mannelijke of vrouwelijke kinderen met een bevestigde diagnose van TSC (Roach criteria; Roach 1998, of DNA bevestigd);
- Niet ouder dan 4 maanden op het moment van inclusie;
- Geen klinische aanvallen gezien door ouders/verzorgers of op het baseline videoEEG;
- Schriftelijke toestemming van de ouders. Het is mogelijk om alleen toestemming te geven voor het observationele deel van de studie. In dat geval zal het kind niet deelnemen aan de RCT.

E.4

Principal exclusion criteria

- Any type of seizures observed till baseline visit,
- Antiepileptic treatment at or prior to study entry,
- Contraindications to MRI,
- Any severe and/or uncontrolled medical condition that is considered by the investigator as possibly affecting the EPISTOP analyses or procedures.

- Elke type epileptische aanvallen, geobserveerd tot aan inclusie;
- Behandeling met anti-epileptica voor of ten tijde van inclusie;
- Contra-indicaties voor MRI-onderzoek;
- Elke ernstige medische aandoening die volgens de onderzoeker mogelijk de procedures en/of analyses van EPISTOP kan beinvloeden.

E.5 End points

E.5.1

Primary end point(s)

Primary endpoint of the study is the collection of a set of molecular and clinical biomarkers in full analysis set of patients, including all TSC infants participating in the study and the control subjects.

De primaire uitkomstparameter van de studie is de collectie van een set van moleculaire en klinische biomarkers, bij alle deelnemers aan het onderzoek, zowel kinderen met TSC, als controles.

E.5.1.1

Timepoint(s) of evaluation of this end point

vEEG will be performed every 4 weeks (± 1 week) in the children under the age of 6 months, then every 6 weeks (± 1 week) in children under 12 months, and every 8 weeks (± 1 week) thereafter.
MRI will be performed at baseline (unless patient had an MRI performed within 1 month before baseline visit and an additional scan cannot be performed without general anaesthesia) and then as clinically indicated, but not later than at the age of 2 years.
Neuropsychological assessment using a specially designed targeted battery of test will be performed every 6 months.
Blood samples will be collected at study entry, at the onset of epileptiform discharges on vEEG or at the age of 6 months, whichever is applicable, at the onset of clinical seizures and at the end of follow-up (age 2 years)

Er zal elke 4 weken (± 1 week) een videovEEG gemaakt worden bij kinderen jonger dan 6 maanden; daarna elke 6 weken (± 1 week) bij kinderen jonger dan 12 maanden en daarna elke 8 weken tot het einde van de follow-up.
Er zal bij inclusie een MRI-hersenen gemaakt worden (tenzij de patient binnen een maand voor de baseline visit een MRI heeft ondergaan en een extra scan niet kan worden uitgevoerd zonder algehele anesthesie) en daarna wanneer klinisch geïndiceerd, maar niet later dan op de leeftijd van 2 jaar.
Neuropsychologisch onderzoek zal elke 6 maanden plaatsvinden.
Bloedafname zal plaatsvinden bij inclusie, bij het ontstaan van epileptiforme afwijkingen op het EEG of op de leeftijd van 6 maanden, bij de start van klinische aanvallen en aan het einde van de follow-up (2 jaar).

E.5.2

Secondary end point(s)

Key secondary endpoint is better efficacy of antiepileptic treatment in patients diagnosed as epileptic after electroencephalographic epileptiform discharges in comparison to patients diagnosed as having epilepsy after the onset of clinical seizures.

De belangrijkste secundaire uitkomstparameter is het vaststellen van het meest effectieve moment van behandelen: na het ontstaan van epileptiforme EEG afwijkingen of na het ontstaan van klinische aanvallen.

E.5.2.1

Timepoint(s) of evaluation of this end point

The parameters of efficacy assessment include: the distribution of seizure free patients, proportion of patients with drug resistant seizures, proportion of patients with normalized EEG, the neuropsychological outcome recognized as the results in a battery of tests performed at the age of 24 months.

Parameters van effectiviteit omvatten de volgende: de verdeling van aanvalsvrije patienten, de proportie patienten met refractaire epilepsie, de proportie patienten met een genormaliseerd EEG en de uitkomsten van neuropsychologisch onderzoek op de leeftijd van 24 maanden.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

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)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

Yes

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

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Het meest optimale moment van behandelen.

Different time points for treatment of epilepsy.

E.8.2.4

Number of treatment arms in the trial

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

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

Last visit of the last subject

Laatste bezoek van de laatste patient.

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

E.8.9.2

In all countries concerned by the trial 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:

100

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)

Yes

F.1.1.3.1

Number of subjects for this age range:

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)

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

Infants up to 4th month of life can join the study after their caregivers/parents give consent

Zuigelingen tot de leeftijd van 4 maanden kunnen deelnemen aan het onderzoek als hun ouders/verzorgers toestemming geven.

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

100

F.4.2.2

In the whole clinical trial

100

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

geen

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

2014-07-14

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-12-05

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

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