Clinical Trials Register

Summary
EudraCT Number:	2012-002470-31
Sponsor's Protocol Code Number:	MT-1303-E04
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:	2012-09-03
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

2012-002470-31

A.3

Full title of the trial

A phase II, multicentre, randomised, double-blind, parallel group, placebo-controlled, dose-finding study to evaluate the safety and efficacy of three different oral doses of MT-1303 administered for a period of 24 weeks in subjects with relapsing-remitting multiple sclerosis

A.3.1

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

A study to assess safety and effectiveness of the study drug MT-1303 at different dosage strengths

A.4.1

Sponsor's protocol code number

MT-1303-E04

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	Mitsubishi Tanabe Pharma Corporation (MTPC)
B.1.3.4	Country	Japan
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Mitsubishi Tanabe Pharma Corporation (MTPC)
B.4.2	Country	Japan
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Mitsubishi Pharma Europe Ltd (MPE)
B.5.2	Functional name of contact point	Clinical Project Manager
B.5.3	Address:
B.5.3.1	Street Address	Dashwood House, 69 Old Broad Street
B.5.3.2	Town/ city	London
B.5.3.3	Post code	EC2M 1QS
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	00442070655000
B.5.5	Fax number	00442070655050
B.5.6	E-mail	KGreenough@m-pharma.co.uk

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	MT-1303
D.3.2	Product code	MT-1303
D.3.4	Pharmaceutical form	Capsule
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	MT-1303
D.3.9.2	Current sponsor code	MT-1303
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.1
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	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	MT-1303
D.3.2	Product code	MT-1303
D.3.4	Pharmaceutical form	Capsule
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	MT-1303
D.3.9.2	Current sponsor code	MT-1303
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.2
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	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	MT-1303
D.3.2	Product code	MT-1303
D.3.4	Pharmaceutical form	Capsule
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	MT-1303
D.3.9.2	Current sponsor code	MT-1303
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.4
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	Capsule
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

Relapsing-Remitting Multiple Sclerosis

E.1.1.1

Medical condition in easily understood language

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	15.0
E.1.2	Level	PT
E.1.2	Classification code	10063399
E.1.2	Term	Relapsing-remitting 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

To evaluate the safety, tolerability and effects of three oral doses of MT-1303 compared to placebo given for a period of 24 weeks in subjects with relapsing-remitting multiple sclerosis (RRMS) on MRI parameters.

E.2.2

Secondary objectives of the trial

• To evaluate the effects of MT-1303 compared to placebo on clinical outcomes
• To explore the dose-response relationship of three dose levels of MT-1303 in subjects with RRMS
• To evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of MT-1303 and its phosphorylated metabolite (MT-1303-P) in subjects with RRMS
• To evaluate the effects of MT-1303 compared to placebo on quality of life as measured by the Multiple Sclerosis Quality of Life-54 (MSQOL-54)
• To obtain deoxyribonucleic acid (DNA) for exploratory purposes (optional).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. RRMS as defined by the revised McDonald criteria
2. Evidence of recent MS activity defined as either:
• at least one documented relapse in the previous 12 months, OR
• a positive gadolinium (Gd)-enhanced MRI scan within 3 months prior to screening, OR
• at least two documented relapses in the previous 24 months with a positive Gd-enhanced MRI scan within the previous 12 months
3. Expanded Disability Status Score (EDSS) score ≥0.0 and
≤5.5 points.

E.4

Principal exclusion criteria

1. Primary progressive, secondary progressive or progressive relapsing MS at screening
2. Disease duration >15 years combined with an EDSS score ≤2.0
3. Relapse of MS during the Screening Period
4. History or known presence of other neurological disorders likely to render the subject unsuitable for the study
5. History of any of a list of pre-defined cardiovascular diseases
6. History or known presence of any significant central nervous system, infectious, metabolic, oncological, ophthalmological or respiratory system disease or illness likely to render the subject unsuitable for the study
7. Previous exposure to any sphingosine 1-phosphate receptor modulator
8. Receipt of a live vaccine or systemic corticosteroid use within 28 days prior to randomisation
9. Previous treatment with beta-interferons or glatiramer acetate within 14 days prior to randomisation
10. Previous treatment with intravenous immunoglobulin, plasmapheresis, certain immunosuppressants, lymphocyte-depleting therapy, total body irradiation or bone marrow transplantation
11. Need, or likely need for, treatment with Class I or III
anti-arrhythmic drugs or with heart-rate-lowering beta-blockers or calcium-channel blockers, or with any other drugs which can reduce the heart rate
12. Evidence of significant anaemia, thrombocytopenia, leucopoenia or lymphocytopenia, renal or hepatic impairment
13. Clinically significant electrocardiogram (ECG) findings.

E.5 End points

E.5.1

Primary end point(s)

• Total number of monthly MRI Gd-enhanced T1-weighted lesions observed across post-baseline visits (Weeks 8-24)

E.5.1.1

Timepoint(s) of evaluation of this end point

Various timepoints throughout the study - please refer to the detailed Time and Events Schedule in the protocol for full details

E.5.2

Secondary end point(s)

• Total number of monthly MRI Gd-enhanced T1-weighted lesions observed across all scheduled post-baseline visits (Weeks 4-24)
• Total number of and volume of new or enlarged T2-weighted lesions observed across all scheduled post-baseline visits (Weeks 4-24)
• Change from baseline in brain volume at Week 24
• Exploratory Magnetisation Transfer Ratio (MTR)
endpoints detailed in Statistical Analysis Plan (SAP) (selected centres only)
• Clinical endpoints
o Annualised Relapse Rate (ARR) at Week 24
o Change from baseline in total EDSS score and total Multiple Sclerosis Functional Composite (MSFC) score at Week 24

Pharmacodynamic endpoints:
• Lymphocyte counts
• Lymphocyte subsets (selected centres only)

Safety Endpoints:
• Adverse events (AEs)
• Vital signs
• 12-lead ECG
• 3-lead Holter ECG monitoring
• Routine safety laboratory assessments
• Physical examination
• Optical coherence tomography (OCT)

Pharmacokinetic Endpoint:
• MT-1303 and MT-1303-P concentrations

Subject-reported Outcome:
• Change from baseline in MSQOL-54 at Week 24.

E.5.2.1

Timepoint(s) of evaluation of this end point

Various timepoints throughout the study - please refer to the detailed Time and Events Schedule in the protocol for full details

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

Yes

E.6.7

Pharmacodynamic

Yes

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

Yes

E.6.13.1

Other scope of the trial description

Tolerability

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

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

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Belgium

Bosnia and Herzegovina

Bulgaria

Canada

Croatia

Czech Republic

Finland

Germany

Hungary

Italy

Latvia

Lithuania

Poland

Russian Federation

Serbia

Spain

Sweden

Switzerland

Turkey

Ukraine

United Kingdom

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

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

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)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

400

F.1.3

Elderly (>=65 years)

F.1.3.1

Number of subjects for this age range:

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

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.4.2

For a multinational trial

F.4.2.1

In the EEA

250

F.4.2.2

In the whole clinical trial

400

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

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

2012-09-27

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-10-29

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2014-10-23

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