Clinical Trials Register

Summary
EudraCT Number:	2011-000888-27
Sponsor's Protocol Code Number:	GTR001
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-08-19
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

2011-000888-27

A.3

Full title of the trial

Multi-centre, randomized, double-blind, placebo-controlled, parallel-group, 9 month, equivalence trial comparing the efficacy and safety and tolerability of GTR (Synthon BV) to Copaxone® (Teva) in subjects with relapsing remitting multiple sclerosis followed by an open-label 15 month GTR treatment part evaluating the long-term GTR treatment effects

A.3.1

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

A clinical trial comparing the efficacy, and safety and tolerability of two disease modifying MS drugs (GTR and Copaxone®) in patients with relapsing remitting multiple sclerosis for 9 months followed by a 15 month GTR treatment part to evaluate efficacy and safety of long-term GTR treatment.

A.3.2

Name or abbreviated title of the trial where available

GATE

A.4.1

Sponsor's protocol code number

GTR001

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	Synthon BV
B.1.3.4	Country	Netherlands
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	Synthon BV
B.4.2	Country	Netherlands
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	PSI CRO UK Ltd
B.5.2	Functional name of contact point	Barry Crossman
B.5.3	Address:
B.5.3.1	Street Address	Beaumont House, Langford Business Park, Langford Locks, Kidlington
B.5.3.2	Town/ city	Oxford
B.5.3.3	Post code	OX5 1GG
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	004418658552906309
B.5.5	Fax number	00441865855295
B.5.6	E-mail	Barry.Crossman@psi-cro.com

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	glatiramer acetate
D.3.2	Product code	GTR
D.3.4	Pharmaceutical form	Solution for injection in pre-filled syringe
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	glatiramer acetate
D.3.9.1	CAS number	147245-92-9
D.3.9.2	Current sponsor code	GTR
D.3.9.3	Other descriptive name	GTR.ace
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	20
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	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	Copaxone
D.2.1.1.2	Name of the Marketing Authorisation holder	Teva Pharmaceuticals Industries Ltd
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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.3.4	Pharmaceutical form	Solution for injection in pre-filled syringe
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	glatiramer acetate
D.3.9.1	CAS number	147245-92-9
D.3.9.3	Other descriptive name	GLATIRAMER ACETATE
D.3.9.4	EV Substance Code	SUB13971MIG
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	20
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	Solution for injection in pre-filled syringe
D.8.4	Route of administration of the placebo	Subcutaneous 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 is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged.

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	14.1
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 demonstrate that the efficacy of Synthon’s glatiramer acetate (GTR) is equivalent to Copaxone® (TEVA) in subjects with relapsing remitting multiple sclerosis (RRMS) as measured by the number of gadolinium-enhancing lesions on T1-weighted MRIs during the months 7-9.

E.2.2

Secondary objectives of the trial

Blinded phase:
• to compare the efficacy of GTR to Copaxone® based on MRI parameters
• to compare the efficacy of GTR to Copaxone® based on the annualized relapse rate;
• to compare the efficacy of GTR to Copaxone® based on the changes in EDSS;
• to compare the efficacy of GTR to Copaxone® based on the percentage subjects free from disease activity at month 9;
• to compare the percentage of subjects with anti-glatiramer antibodies after GTR and Copaxone® treatment.
Open-label phase:
• to evaluate efficacy, safety and tolerability of long-term (2-years) GTR treatment;
• to evaluate efficacy, safety and tolerability of switching to GTR treatment after previous Copaxone® use.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Willing and able to sign written Informed Consent;
2. Female and male subjects aged 18-55 years inclusive at the time of Informed Consent signing;
3. Diagnosis of RRMS according to the revised McDonald criteria 4. Expanded Disability Status Scale (EDSS) score of 0.0 up to and including 5.5;
5. Neurologically stable with no evidence of relapse within 30 days prior to randomization;
6. Experienced at least 1 relapse in the year before first screening assessment;
7. At least 1 T1-weighted Gadolinium enhancing (T1-GdE) lesion on routine brain MRI taken within 3 months of starting screening or on screening brain MRI (as confirmed by central imaging laboratory);
8. Having a routine brain MRI showing maximally 15 T1-GdE lesions if scan is taken without subject receiving immuno-modulatory treatment, or a routine brain MRI showing maximally 5 T1-GdE lesions when taken while on immune-modulatory treatment, or a screening MRI showing maximally 15 T1-GdE lesions;
9. Must decline initiation or continuation of treatment with other available disease-modifying drugs for MS, for whatever reason, after having been informed about their respective benefits and possible adverse events by the investigator;
10. Female subjects of childbearing potential must agree to practice appropriate contraceptive methods as assessed by the investigator.

E.4

Principal exclusion criteria

1. Any life-threatening, medically unstable or otherwise clinically significant condition or findings other than MS, in particular neoplastic disease, seizure disorders, or psychiatric disease;
2. Any clinically significant deviation from reference ranges in laboratory tests;
3. Positive laboratory test results for human immunodeficiency virus (HIV), HBsAg or HCV at screening;
4. Any significant deviation from reference ranges for hepatic function as defined by either AST (SGOT), ALT (SGPT), GGT, or AP elevated 3-fold or higher beyond the upper limit of the reference range or total bilirubin elevated 2-fold or higher beyond the upper limit of the reference range (in case of Gilbert’s Syndrome, a joint documented decision will be made between the investigator and the Medical Officer);
5. Positive urine drug screen or history of substance abuse within the year before screening (any use of illicit or prescription drugs or alcohol constituting an abuse pattern in the opinion of the investigator);
6. Having been treated with or having received
a. at any time:
• glatiramer acetate, cladribine, rituximab, cyclophosphamide, alemtuzumab, or other immunosuppressive treatments with effects potentially lasting for more than 6 months;
• total lymphoid irradiation or bone marrow transplantation;
b. within one year before screening:
• mitoxantrone, but subject cannot be enrolled when mitoxantrone was taken at a cumulative lifetime dosing above 100 mg/m2;
c. within 6 months before screening:
• fingolimod, immunoglobulins and/or monoclonal antibodies (including natalizumab), leflunomide, or putative MS treatments;
• chronic oral or injected corticosteroids or injected ACTH (more than 30 consecutive days);
d. within 3 months before screening:
• azathioprine, methotrexate;
• plasma exchange;
• any other experimental intervention, in particular experimental drugs;
e. within 1 month before screening:
• Interferon-β 1a or 1b;
• short-term oral or injectable corticosteroids for treatment of a relapse;
• short-term ACTH;
7. Having, in the opinion of the investigator, consecutively failed on efficacy grounds two full and adequate courses of accepted treatment modalities (normally at least one year of treatment for each);
8. Pregnancy or breastfeeding;
9. Known hypersensitivity to gadolinium-containing products, glatiramer acetate or mannitol;
10. Having an estimated glomerular filtration rate (eGFR) < 50 mL/min/1.73m2;
11. Inability to undergo (repeat) MRI investigations as judged by the investigator, e.g., due to claustrophobia, metal implants or fragments, tattoos or permanent make-up;
12. Any reason why, in the investigator's opinion, the subject should not participate.

E.5 End points

E.5.1

Primary end point(s)

The number of Gadolinium enhancing lesions.

E.5.1.1

Timepoint(s) of evaluation of this end point

the months 7-9 after start of treatment

E.5.2

Secondary end point(s)

• MRI parameters;
• Annualized relapse rate;
• EDSS change from baseline;
• Percentage subjects “Free from disease activity”;
• Percentage of subjects with anti-glatiramer antibodies formation.

E.5.2.1

Timepoint(s) of evaluation of this end point

as per trial objectives and trial flowchart, page 7 and 8 of protocol

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)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

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

Yes

E.8.1.7.1

Other trial design description

followed by open-label 15 month GTR treatment

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

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

Belarus

Bulgaria

Croatia

Czech Republic

Germany

Italy

Lithuania

Poland

Romania

Russian Federation

Serbia

Slovakia

Spain

Ukraine

United Kingdom

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

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

F.1.1