Clinical Trials Register

Summary
EudraCT Number:	2010-018705-11
Sponsor's Protocol Code Number:	ONO-4641POU007
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2010-10-14
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

Germany - BfArM

A.2

EudraCT number

2010-018705-11

A.3

Full title of the trial

A SAFETY AND EFFICACY EXTENSION STUDY OF ONO-4641 IN PATIENTS WITH RELAPSING-REMITTING MULTIPLE SCLEROSIS

A.3.1

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

A SAFETY AND EFFICACY EXTENSION STUDY OF ONO-4641 IN PATIENTS WITH RELAPSING-REMITTING MULTIPLE SCLEROSIS

A.4.1

Sponsor's protocol code number

ONO-4641POU007

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01226745

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	Merck KGaA
B.1.3.4	Country	Germany
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	Merck KGaA
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Merck KGaA
B.5.2	Functional name of contact point	Communication Center Merck KGaA
B.5.3	Address:
B.5.3.1	Street Address	Frankfurter Strasse 250
B.5.3.2	Town/ city	Darmstadt
B.5.3.3	Post code	64293
B.5.3.4	Country	Germany
B.5.4	Telephone number	496151725200
B.5.5	Fax number	496151722000
B.5.6	E-mail	service@merck.de

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	ONO-4641/ MSC2430913A
D.3.2	Product code	ONO-4641/ MSC2430913A
D.3.4	Pharmaceutical form	Film-coated 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.3.9.2	Current sponsor code	ONO-4641/ MSC2430913A
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	0.05
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	ONO-4641/ MSC2430913A
D.3.2	Product code	ONO-4641/ MSC2430913A
D.3.4	Pharmaceutical form	Film-coated 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.3.9.2	Current sponsor code	ONO-4641/ MSC2430913A
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: 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	ONO-4641/ MSC2430913A
D.3.2	Product code	ONO-4641/ MSC2430913A
D.3.4	Pharmaceutical form	Film-coated 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.3.9.2	Current sponsor code	ONO-4641/ MSC2430913A
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	0.15
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

Relapsing-remitting Multiple Sclerosis

E.1.1.1

Medical condition in easily understood language

Multiple sclerosis is the result of damage to myelin a protective sheath surrounding nerve fibres of the central nervous system. This interferes with messages between the brain and rest of the body.

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	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

The primary objective of this 225-week active-drug Extension Study is to evaluate the continuing safety and efficacy of ONO-4641 in patients with relapsing-remitting multiple sclerosis (RRMS) in patients who have completed an initial 26-week study (ONO-4641POU006).

E.2.2

Secondary objectives of the trial

N/A

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Patients will be eligible to participate in this study if they meet all of the following criteria:

1. Completed 26 weeks of double-blind phase of Study ONO-4641POU006.

2. From participation and throughout the duration of the study, male and female subjects of childbearing potential (ie, non-sterilized, premenopausal females) who are sexually active must use adequate contraception until 2 months after the last dose of study medication. An acceptable method of contraception is defined as one that has no failure rate or a <1% failure rate. It is recommended to combine a hormonal method (PEARL index < 1) with a barrier method. The following contraception methods are especially reliable according to the guidelines of the German Association of Gynaecology and Obstetrics:

• Oral contraceptive pill with estrogen and gestagen (no micro pill)
• Vaginal ring (i.e.. NuvaRing®)
• Contraception plaster (i.e. EVRA®)
• Estrogen-free ovulation inhibitor (i.e. Cerazette®)
• Intradermal contraception sticks with progesteron (i.e. Implanon®)
• an injection of gestagen every 3 months
• Contraceptive coil with Progesteron (i.e. Minera®)
• Contraception with double barrier method (condom, contraceptive sponge, diaphragm, or vaginal ring with spermicidal gel or foam)

Male subjects and women of child bearing potential will be provided with information on acceptable methods of contraception as part of the subject informed consent process, and will be advised of the requirements for avoidance of pregnancy until 2 months after the last dose of study medication. Subjects will receive continued guidance with respect to the avoidance of pregnancy as part of the study procedures. In addition to a negative serum hCG pregnancy test throughout the study period, subjects also must have a negative urine hCG pregnancy test on the day of the first dose of study medication, prior to receiving the first dose of the extension study drug.

4. Able and willing to provide signed, written, Informed Consent.

E.4

Principal exclusion criteria

Patients will not be eligible to participate in this study if any of the following criteria apply:

1. Presence of any dermatological abnormalities during Study ONO-4641POU006 that in the opinion of the investigator or the Sponsor (Ono Pharmaceutical Co., Ltd.) could increase the risk of the patient developing a skin cancer.

2. In the opinion of the Investigator, a patient who may not be able to cooperate fully with the study staff, may have difficulty in some study requirements, or is otherwise not qualified for the study.

3. Any of the following cardiovascular conditions:
a. History of significant cardiac (e.g. coronary heart disease, myocarditis, cardiomyopathy, heart failure NYHA II-IV) condition;
b. History of syncope;
c. Resting heart rate < 55 beat/min based on ECG at Visit 9 predose or history of any cardiac conditions that might increase the risk of a significant reduction in heart rate (e.g. any delay in the cardiac stimulus conduction on ECG);
d. Any medical condition that poses a significant risk of predisposing a patient to induction of cardiac arrhythmias (e.g. status post catheter ablation, hyperkalemia [defined as 2 consecutive measures of K+ above 6.0 mEq/L]).

E.5 End points

E.5.1

Primary end point(s)

The number of Gd-enhanced lesions, lesion volume, and brain volume obtained by MRI at Weeks 13, 16, 20, 4, 27, 29, Follow up Visit 30 and Early Termination Visit will be compared with that of the baseline of the Extension Study

E.5.1.1

Timepoint(s) of evaluation of this end point

Weeks 13, 16, 20, 4, 27, 29, Follow up Visit 30 and Early Termination Visit

E.5.2

Secondary end point(s)

N/A

E.5.2.1

Timepoint(s) of evaluation of this end point

N/A

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

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

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

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

Canada

Japan

Russian Federation

Ukraine

United States

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

The end of trial for POU007, including the current extension, is based on the last patient last visit (V29) - projected 1757 days after 15April2011, which is the latest date for the predose evaluation visit on Day 1 (Visit 2) for the core study (POU006).

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