Clinical Trials Register

Summary
EudraCT Number:	2020-004511-27
Sponsor's Protocol Code Number:	S64647
National Competent Authority:	Belgium - FPS Health-DGM
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-01-21
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

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A. Protocol Information

A.1

Member State Concerned

Belgium - FPS Health-DGM

A.2

EudraCT number

2020-004511-27

A.3

Full title of the trial

Add-on clioquinol in drug-resistant childhood epilepsy: an exploratory study

Clioquinol bij kinderen met pharmaco-resistente epilepsie

A.3.1

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

Administering Clioquinol to children with drug-resistant epilepsy

Clioquinol geven aan kinderen met drug resistente epilepsie

A.3.2

Name or abbreviated title of the trial where available

CLIOKID: clioquinol for Drug Resistant Epilepsy in Kids

CLIOKID: clioquinol voor drug resistente epilepsie in kinderen

A.4.1

Sponsor's protocol code number

S64647

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 Hospital Leuven
B.1.3.4	Country	Belgium
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	University Hospital Leuven
B.4.2	Country	Belgium
B.4.1	Name of organisation providing support	Catholic University Leuven
B.4.2	Country	Belgium
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	University Hospital Leuven
B.5.2	Functional name of contact point	Clinical Trial Assistant
B.5.3	Address:
B.5.3.1	Street Address	Herestraat 49
B.5.3.2	Town/ city	Leuven
B.5.3.3	Post code	3000
B.5.3.4	Country	Belgium
B.5.4	Telephone number	+3216345495
B.5.5	Fax number	+3216343889
B.5.6	E-mail	eva.gielis@uzleuven.be

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	Clioquinol
D.3.4	Pharmaceutical form	Oral solution
D.3.4.1	Specific paediatric formulation	Yes
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	CLIOQUINOL
D.3.9.1	CAS number	130-26-7
D.3.9.3	Other descriptive name	PBT-1
D.3.9.4	EV Substance Code	SUB06669MIG
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	100
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

Drug resistant epilepsy in children

Drug resistente epilepsie in kinderen

E.1.1.1

Medical condition in easily understood language

Drug resistant epilepsy in children

Drug resistente epilepsie in kinderen

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	21.0
E.1.2	Level	PT
E.1.2	Classification code	10015037
E.1.2	Term	Epilepsy
E.1.2	System Organ Class	10029205 - Nervous system 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 study whether add-on clioquinol decreases the seizure frequency and severity in children with drug-resistant epilepsy.

Nagaan of add-on clioquinol de aanvalsfrequentie en -intensiteit bij kinderen met drug resistente epilepsie verlaagt.

E.2.2

Secondary objectives of the trial

a. Safety during trial (systematic recording of adverse events)
b. Assessment of seizure severity with the National Hospital Seizure Severity Scale (NHS3 scale)
c. Assessment of overall impact of seizures, medication
side effects, comorbidities, and overall Quality of Life (QoL) using the Personal Impact of Epilepsy Scale (PIES)

a. Veiligheid tijdens de proef (systematische registratie van ongewenste voorvallen)
b. Beoordeling van de ernst van de inbeslagneming met de National Hospital Seizure Severity Scale (NHS3-schaal)
c. Beoordeling van het totale effect van inbeslagnemingen, medicatie
bijwerkingen, comorbiditeiten en algemene kwaliteit van leven (QoL) met behulp van de persoonlijke impact van de epilepsieschaal (PIES)

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Voluntary written informed consent of the participant or their legally authorized representative has been obtained prior to any screening procedures
2. In females with child bearing potential: negative pregnancy test or use of highly effective methods of birth control; defined as those that, alone or in combination, result in low failure rate (i.e., less than 1% per year) when used consistently and correctly; such as implants, injectables, combined oral contraceptives, some intra-uterine devices, true sexual abstinence (i.e. refraining from heterosexual intercourse during the entire period of risk associated with the Trial treatment(s)) or commitment to a vasectomized partner
3. Age ≥ 4 years and < 18 years at time of inclusion
4. Weight ≥ 20 kg at time of inclusion
5. Well defined epilepsy history with convulsive seizures (with observable and countable motor component)
6. Drug-resistant epilepsy: before inclusion failure of at least 2 AEDs
7. Drug-resistant epilepsy: ≥ 4 seizures in the 2 week prospective period (baseline) before visit 2, not all (4) seizures observed in 1 of the 2 weeks. Baseline period can be extended with 1 or 2 weeks.
8. The patient is at the moment of inclusion on max 3 anti-epileptic drugs (VNS and ketogenic diet not included)

1. De deelnemer of zijn wettelijke vertegenwoordiger heeft voorafgaand aan de screening vrijwillig schriftelijk en op basis van informatie toestemming gegeven.
2. Bij vrouwen met een potentieel kind: negatieve zwangerschapstest of gebruik van zeer effectieve methoden voor geboortebeperking; gedefinieerd als methoden die, alleen of in combinatie, resulteren in een laag faalpercentage (d.w.z. minder dan 1% per jaar) bij consequent en correct gebruik; zoals implantaten, injectables, gecombineerde orale anticonceptiemiddelen, sommige intra-uteriene hulpmiddelen, ware seksuele onthouding (d.w.z. afzien van heteroseksuele gemeenschap gedurende de gehele risicoperiode die met de proefbehandeling(en) gepaard gaat) of verbintenis met een vasectomized partner.
3. Leeftijd ≥ 4 jaar en < 18 jaar op het moment van opname
4. Gewicht ≥ 20 kg op het moment van opname
5. Goed gedefinieerde epilepsiegeschiedenis met motorische aanvallen (met waarneembare en telbare motorische component)
6. Drugsresistente epilepsie: voordat de opname van ten minste 2 AED's mislukt.
7. Drugsresistente epilepsie: ≥ 4 aanvallen in de 2 weken voor bezoek 2 (basisperiode), niet alle (4) aanvallen waargenomen in 1 van de 2 weken. De basisperiode kan worden verlengd met 1 of 2 weken.
8. De patiënt is op het moment van opname op max. 3 anti-epileptica (VNS en ketogeen dieet niet inbegrepen)

E.4

Principal exclusion criteria

1. Participant has a history of liver or kidney disease. Children with a co-existing active neuropathy (such as neuritis optica, transverse myelitis)
2. Asian etnicity
3. Abnormal low blood level of vitamin B12 or Zn
4. Patients with hypothyroidism
5. Any disorder, which in the Investigator’s opinion might jeopardize the participant’s safety or compliance with the protocol
6. Any prior or concomitant treatment(s) that might jeopardize the participant’s safety or that would compromise the integrity of the Trial
7. Exposure to clioquinol before the trial
8. Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using an adequate, highly effective contraceptive
9. Participation in an interventional Trial with an IMP or device

1. Deelnemer heeft een geschiedenis van lever- of nierziekte. Kinderen met een co-existente actieve neuropathie (zoals neuritis optica, transversale myelitis)
2. Aziatische etniciteit
3. Abnormale lage bloedspiegel van vitamine B12 of Zn
4. Patiënten met hypothyreoïdie
5. Elke aandoening die naar het oordeel van de onderzoeker de veiligheid van de deelnemer of de naleving van het protocol in gevaar kan brengen
6. Elke voorafgaande of gelijktijdige behandeling(en) die de veiligheid van de deelnemer in gevaar kan (kunnen) brengen of die de integriteit van het proces in gevaar kan (kunnen) brengen.
7. Blootstelling aan clioquinol vóór het onderzoek
8. Vrouwen die zwanger zijn, borstvoeding geven of van plan zijn zwanger te worden of zwanger te worden en geen adequaat, zeer effectief anticonceptiemiddel gebruiken
9. Deelname aan een interventieproef met een gvo of apparaat

E.5 End points

E.5.1

Primary end point(s)

Efficacy of Clioquinol will be measured:
a. percentage of 50% responders after 2 weeks and 10 weeks exposure to low (1mg/kg BID) and higher dose (4mg/kg BID) of clioquinol respectively (visit 3 and 5)
b. median % reduction of the seizure frequency at visit 5

De werkzaamheid van Clioquinol zal worden gemeten:
a. percentage van 50% respondenten na 2 weken en 10 weken blootstelling aan respectievelijk lage (1mg/kg BID) en hogere dosis (4mg/kg BID) clioquinol (bezoek 3 en 5)
b. mediaan % verlaging van de inbeslagnemingsfrequentie bij het bezoek 5

E.5.1.1

Timepoint(s) of evaluation of this end point

A and B is evaluated on visit 3 and 5.

A en b worden bij bezoek 3 en 6 geëvalueerd.

E.5.2

Secondary end point(s)

(Cardiac) Safety, QoL and seizure severity

(Cardiale) Veiligheid, QoL en ernst van de aanvallen

E.5.2.1

Timepoint(s) of evaluation of this end point

ECG: Screening and visit 5
AE + Concomitant medication: every visit
QoL and seizure severity: Visit 2, 3, 5 and 6

ECG: Screening en bezoek 5
AE + medicatie: elk bezoek
QoL en de ernst van de aanvallen: Bezoek 2, 3, 5 en 6

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

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

E.8.1.1

Randomised

E.8.1.2

Open

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)

E.8.2.2

Placebo

E.8.2.3

Other

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

Last visit, last patient

Laatste bezoek, laatste patiënt

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)

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)

Yes

F.1.1.6.1

Number of subjects for this age range:

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 For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2021-01-21.

Yes

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.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)

Subjects who show a sustained and >75% seizure frequency reduction at the end of core trial, will be offered to continue in an extension phase of the trial. Follow up visits will be organized every 12 weeks. Only when the response to the drug remains >75% the patient can continue in the extension phase.

Proefpersonen die aan het einde van het kern onderzoek een aanhoudende en >75% vermindering van de aanvalsfrequentie laten zien, zullen worden aangeboden om door te gaan in een extensie fase van de proef. Er zullen om de 12 weken follow-up bezoeken worden georganiseerd. Alleen wanneer de respons op het geneesmiddel >75% blijft, kan de patiënt doorgaan in de extensie fase.

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

2021-08-05

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-01-06

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

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