Clinical Trials Register

Summary
EudraCT Number:	2013-002419-87
Sponsor's Protocol Code Number:	008722
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2014-02-07
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

2013-002419-87

A.3

Full title of the trial

Oxcarbazepine as a neuroprotective agent in MS: phase 2a trial

A.3.1

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

PROXIMUS (PRotective role of OXcabazepine In MUltiple Sclerosis)

A.3.2

Name or abbreviated title of the trial where available

PROXIMUS - PRotective role of OXcabazepine In MUltiple Sclerosis

A.4.1

Sponsor's protocol code number

008722

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	Queen Mary University London
B.1.3.4	Country	United Kingdom
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	National MS Society
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Barts Health NHS Trust
B.5.2	Functional name of contact point	Sally Burtles
B.5.3	Address:
B.5.3.1	Street Address	Joint Research Management Office QM Innovation Building 5 Walden Street
B.5.3.2	Town/ city	London
B.5.3.3	Post code	E1 2EF
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	02078827260
B.5.6	E-mail	sponsorsrep@bartshealth.nhs.uk

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Comparator
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	Trileptal
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Pharmaceuticals UK 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	Oxcarbazepine
D.3.4	Pharmaceutical form
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	oxcarbazepine
D.3.9.3	Other descriptive name	Trileptal
D.3.9.4	EV Substance Code	AS1
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.3	Concentration number	150
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
D.8.3	Pharmaceutical form of the placebo	Coated tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Multiple sclerosis

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	19.0
E.1.2	Level	PT
E.1.2	Classification code	10028245
E.1.2	Term	Multiple sclerosis
E.1.2	System Organ Class	10029205 - Nervous system disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Does oxcarbazepine protect people with multiple sclerosis (PwMS) from nerve loss? When we compare PwMS who take oxcarbazepine for one year to PwMS who take placebo, is the level of neurofilament light (NFL), a marker of nerve loss, in the CSF significantly reduced?

E.2.2

Secondary objectives of the trial

Can we detect reduction of nerve loss after 6 month of treatment with oxcarbazepine, as measured by lower levels of NFL in the CSF?

Can we detect a change in conventional clinical outcome measure such as the EDSS, 9-hole peg test and the MSIS-29 v2 and neurocognitive tests such as single digit modalities test (SDMT) at the end of the study?

Will will also use conventional and innovative imaging methods such as brain MRI scans and (optico-coherence tomography) OCT and will use CSF, serum and cells to analyse other markers of the effect of degeneration/neuroprotection.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. A diagnosis of definite multiple sclerosis
2. Treatment with DMDs for MS for at least 6 months prior to baseline visit*.
3. CSF NFL level ≥ 0.380ng/mL
4. EDSS score ≥3.5 and ≤ 6.0 at screening
5. No history of relapses in the 6 months prior to the baseline visit
6. A history of slow progression of disability, objective or subjective, over a period of at least 6 months prior to baseline
7. Age 18-60 years at screening

* Temporary interruption is permitted at the discretion of the investigator for a period of up to 8 weeks to prevent inflammatory MS reactivation. The cases where this could happen include for example switching DMDs that require a washout period as per clinical practice. When there are safety concerns, as in Lymphopenia or other side effects induced by the DMD, the interruption period can exceed 8 weeks as per clinical need. If reactivation of MS occurs with a relapse the investigator will assess if this meets withdrawal criteria 6.

E.4

Principal exclusion criteria

1. Pregnant or breastfeeding or unwilling to use adequate contraception*.
2. Participants with a diagnosis of primary progressive PP MS or primary relapsing PR MS.
3. A clinical relapse or pulsed intravenous/ oral steroids for MS relapse in the 6 months preceding the baseline assessment.
4. Participants presenting with medical disorder deemed severe or unstable by the CI such as poorly controlled diabetes or arterial hypertension, severe cardiac insufficiency, unstable ischemic heart disease, abnormal liver function tests (>2.5 times ULN) and abnormal complete blood count (in particular leukopenia, as defined by a lymphocyte count <500, neutrophil count <1.5 or platelet count <100, or thrombocytopenia <1.5 LLN), or any medical condition which, in the opinion of the investigator, would pose additional risk to the participant.
5. Infection with hepatitis B or hepatitis C or human immunodeficiency virus.
6. Exposure to any other investigational drug within 30 days of enrolment in the study.
7. Judged clinically to have a suicidal risk in the opinion of the investigator based upon a clinical interview and the Columbia Suicide-Severity Rating Scale (CSSRS).
8. Prior history of malignancy unless an exception is granted by the investigator.
9. History of uncontrolled drug or alcohol abuse within 6 months prior to screening.
10. Past untoward reactions to OxCbz or Cbz
11. Participants receiving OxCbz or Cbz in the previous 12 weeks from baseline.

*Adequate methods of contraception are non hormonal methods such as barrier methods, intrauterine devices, surgical sterilisation (undergone by the participant or their partner). Female participants using hormonal only forms of contraception will be required to use an additional barrier method. True abstinence can be considered an acceptable method of contraception when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the duration of a trial, and withdrawal are not acceptable methods of contraception. Non sexually active participants or those in same sex relationships will not be required to commence contraception.

E.5 End points

E.5.1

Primary end point(s)

The primary objective is to assess whether OxCbz has a neuroprotective effect in participants with early SP or stable RRMS with history of progression, as measured by the stabilization or decrease of CSF NFL levels.

E.5.1.1

Timepoint(s) of evaluation of this end point

This endpoint is being evaluated from Baseline to 48 weeks post treatment.

E.5.2

Secondary end point(s)

Change over 48 weeks of the study using clinical outcome measures: EDSS 30, and the Questionnaires (Including SF36, MSWS, MSIS-29 v2, Patient Pain Assessment, Patient Fatigue Assessment) and neurocognitive tests such as single digit modalities test (SDMT.

Relative reduction of CSF NFL levels from baseline to 24 weeks and from 24 to 48 weeks.

E.5.2.1

Timepoint(s) of evaluation of this end point

Timelines outlined above and baseline, 24 weeks and 48 weeks.

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

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

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

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

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 Patient's Last Visit.

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

F.1.1