Clinical Trials Register

Summary
EudraCT Number:	2013-000531-27
Sponsor's Protocol Code Number:	43510
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	GB - no longer in EU/EEA
Date on which this record was first entered in the EudraCT database:	2015-03-27
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

UK - MHRA

A.2

EudraCT number

2013-000531-27

A.3

Full title of the trial

Corticosteroids or clobazam for ESES syndrome: a European, multicenter, randomized, controlled clinical trial

A.3.1

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

Clinical trail in children with ESES syndrome

A.3.2

Name or abbreviated title of the trial where available

RCT in children with ESES syndrome

A.4.1

Sponsor's protocol code number

43510

A.5.1

ISRCTN (International Standard Randomised Controlled Trial) Number

ISRCTN42686094

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	University Medical Center Utrecht
B.1.3.4	Country	Netherlands
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	Dutch Epilepsy Fund
B.4.2	Country	Netherlands
B.4.1	Name of organisation providing support	Wilhelmina Research Fund
B.4.2	Country	Netherlands
B.4.1	Name of organisation providing support	European Clinical Research Infrastructures Network (ECRIN)
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 Center Maastricht
B.5.2	Functional name of contact point	Knaepen
B.5.3	Address:
B.5.3.1	Street Address	Oxfordlaan 70
B.5.3.2	Town/ city	6229 EV Maastricht, Postbus 5800
B.5.3.3	Post code	6202 AZ
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	0031433872132
B.5.5	Fax number	0031433872042
B.5.6	E-mail	liesbeth.knaepen@mumc.nl

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	Deltacortril
D.2.1.1.2	Name of the Marketing Authorisation holder	Alliance Pharmaceuticals Limited
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	Deltacortril
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	prednisolone
D.3.9.1	CAS number	H02AB06
D.3.9.4	EV Substance Code	AS2
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.IMP: 2
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	Solu-Medrone
D.2.1.1.2	Name of the Marketing Authorisation holder	Pharmacia Limited
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	Solu-Medrone
D.3.4	Pharmaceutical form	Powder for injection
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	methylprednisolone sodium succinate
D.3.9.1	CAS number	83-43-2
D.3.9.4	EV Substance Code	AS3
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.IMP: 3
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	Tapclob
D.2.1.1.2	Name of the Marketing Authorisation holder	Martindale Pharmaceuticals Ltd
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	Tapclob
D.3.4	Pharmaceutical form	Oral suspension
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Clobazam
D.3.9.1	CAS number	22316-47-8
D.3.9.4	EV Substance Code	AS4
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Electrical Status Epilepticus in Sleep (ESES)

E.1.1.1

Medical condition in easily understood language

Rare epilepsy syndrome which manifests itself during sleep in children.

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	17.1
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

To compare the effects on cognition of treatment with corticosteroids or clobazam in children with ESES syndrome.

E.2.2

Secondary objectives of the trial

1. To compare the effects of treatment with corticosteroids or clobazam, an anti-epileptic drug, in children with ESES syndrome, as assessed with EEG (a method of recording electrical brain activity).
2. To compare the effects of treatment with corticosteroids or clobazam in children with ESES syndrome on the incidence of seizures.
3. To compare the side effects and tolerability of treatment with corticosteroids or clobazam in children with ESES syndrome.
4. To compare the effects of treatment with corticosteroids or clobazam in children with ESES syndrome
5. To assess demographic and disease-related predictive factors, including immunological factors, of success of treatment with corticosteroids or clobazam in children with ESES syndrome.
6. To identify a marker for disease activity and treatment response.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

· Age 2 up to 12 years (not including children of 12 years old);
· A diagnosis within six months prior to study inclusion (preferably as close to inclusion as possible) of either:
o Bilateral sleep-induced epileptiform activity with SWI in > 85% of nonREM sleep and developmental delay, arrest, or regression (“typical ESES syndrome”);
o Arrest or regression of development and bilateral sleep-induced epileptiform activity with a SWI in > 50%, or unilateral sleep induced epileptiform activity with SWI in > 85% of nonREM sleep (“atypical ESES syndrome”);
o Regression of development and unilateral epileptiform activity with a SWI of > 50%
of nonREM sleep (“atypical ESES syndrome”);
· No previous treatment with either corticosteroids or clobazam
· No current treatment nor in the previous three months with carbamazepine, oxcarbazepine, vigabatrin, tiagabine, gabapentin and pregabalin; These drugs are known to possibly worsen the outcome in children with ESES syndrome and may therefore influence treatment result. Furthermore, these drugs can increase the SWI during sleep and may cause an electrographic pattern fulfilling the criteria for ESES. Inclusion of such cases with possible “treatment induced ESES” is not desirable.
· Written informed consent by parents / legal representatives

E.4

Principal exclusion criteria

· Patients with a SWI during wakefulness of > 50%
· Acute or chronic infectious disease (e.g. TB, HIV)
· Immunodeficiency
· Severe osteopenia/osteoporosis
· Diabetes
· Cushing syndrome
· Severe respiratory insufficiency
· Severe liver failure
· Severe ulcera
· Any other condition that, in the investigator’s judgement, contra-indicates the use of corticosteroids or clobazam.

E.5 End points

E.5.1

Primary end point(s)

Primary outcome measure (at six months)
Cognitive functioning:
· Intelligence quotient, or developmental quotient
· Cognitive sumscore (Neurpsychological assessment)
Improvement is defined as statistically significant when improved by at least 75% of the standard deviation (SD).
(Any positive change may be clinically relevant.)

E.5.1.1

Timepoint(s) of evaluation of this end point

at six months

E.5.2

Secondary end point(s)

· individual absolute test results, and IQ scores; improvement is defined as statistically significant when increased by at least 75% of the SD
· the spike wave index during non-REM sleep improvement is defined as SWI of less than 25%;
· seizure frequency; improvement is defined as 50% or more decrease as compared with baseline;
· assessment of global daily functioning assessed with a VAS score (-5 to 5)
· safety and tolerability, as assessed by the occurrence of serious adverse events;
· differences in pro-inflammatory cytokine levels in patients with ESES who respond to either treatment strategies compared to none-responders.

E.5.2.1

Timepoint(s) of evaluation of this end point

at six and 18 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

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

Yes

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

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

Yes

E.8.1.7.1

Other trial design description

Blinded outcome assessment by clinical neurophysiologist and neuropsychologist

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

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

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

The end of the trial is defined as 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

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