E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsing-remitting Multiple Sclerosis (RR MS) |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 16.1 |
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 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the efficacy of Glatiramer Acetate (GA) injection 40 mg administered three times a week compared to placebo in subjects with RRMS, as measured by the number of confirmed relapses during the 12 months placebo controlled phase.
Assessment of safety and tolerability |
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E.2.2 | Secondary objectives of the trial |
- To assess the effect of Glatiramer Acetate (GA) injection 40 mg administered three times a week compared to placebo, on the cumulative number of new/enlarging T2 lesions taken at month 6 and12 (end of placebo-controlled phase).
- To assess the effect of Glatiramer Acetate (GA) injection 40 mg administered three times a week compared to placebo, on the cumulative number of enhancing lesions on T1-weighted images taken at months 6 and 12 (end of placebo-controlled phase).
- To assess the effect of Glatiramer Acetate (GA) injection 40 mg administered three times a week compared to placebo on the development of brain atrophy as defined by the percent brain volume change from baseline to the end of the placebo-controlled phase.
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Ancillary studies:
- Anti-GA antibodies: Serum samples to detect anti-GA specific antibodies
- PBL Proliferation: Blood samples for evaluation of PBL proliferation in response to GA, as well as other immunological parameters
- Pharmacogenetics (PGx): Exploring the association between genetic polymorphism and response to GA in terms of clinical, MRI and safety parameters.
- An additional MRI will be performed at month 36 OL extension before and
after Gadolinium administration, for subjects that sign the additional MRI
ICF.This assessment will provide data for long term use of 40mg TIW |
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E.3 | Principal inclusion criteria |
1. Subjects must have a confirmed and documented MS diagnosis as defined by the Revised McDonald criteria [Ann Neurol 2005: 58:840-846], with a relapsing-remitting disease course.
2. Subjects must be ambulatory with an EDSS score of 0-5.5 in both screening and baseline visits.
3. Subjects must be in a relapse-free, stable neurological condition and free of corticosteroid treatment [intravenous (IV), intramuscular (IM) and/or per os (PO)] or ACTH (Adrenocorticotropic hormone) 30 days prior to screening (month -1) and between screening and baseline (month 0) visits.
4. Subjects must have experienced one of the following:
- At least one documented relapse in the 12 months prior to screening, or
- At least two documented relapses in the 24 months prior to screening, or
- One documented relapse between 12 and 24 months prior to screening with at least one documented T1-Gd enhancing lesion in an MRI performed within 12 months prior to screening.
5. Subjects must be between 18 and 55 years of age, inclusive.
6. Women of child-bearing potential must practice an acceptable method of birth control [acceptable methods of birth control in this study include: surgical sterilization, intrauterine devices, oral contraceptive, contraceptive patch, long-acting injectable contraceptive, partner’s vasectomy or a double-barrier method (condom or diaphragm with spermicide)].
7. Subjects must be able to sign and date a written informed consent prior to entering the study.
8. Subjects must be willing and able to comply with the protocol requirements for the duration of the study. |
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E.4 | Principal exclusion criteria |
1. Subjects with progressive forms of MS.
2. Use of experimental or investigational drugs, and/or participation in drug clinical studies within the 6 months prior to screening.
3. Use of immunosuppressive agents (including Mitoxantrone and Fingolimod) or cytotoxic agents within 6 months prior to the screening.
4. Use of natalizumab (Tysabri®) or any other monoclonal antibodies within 2 years prior to screening.
5. Use of cladribine within 2 years prior to screening.
6. Previous treatment with immunomodulators [including IFNβ 1a and 1b, and IV Immunoglobulin (IVIg)] within 2 months prior to screening.
7. Previous use of GA or any other glatiramoid.
8. Chronic (more than 30 consecutive days) systemic (IV, PO or IM) corticosteroid treatment within 6 months prior to screening visit.
9. Previous total body irradiation or total lymphoid irradiation.
10. Previous stem-cell treatment, autologous bone marrow transplantation or allogenic bone marrow transplantation.
11. Pregnancy or breastfeeding.
12. Subjects with a clinically significant or unstable medical or surgical condition that would preclude safe and complete study participation, as determined by medical history, physical exams, ECG, abnormal laboratory tests and chest X-ray. Such conditions may include hepatic, renal or metabolic diseases, systemic disease, acute infection, current malignancy or recent history (5 years) of malignancy, major psychiatric disorder, history of drug and/or alcohol abuse and allergies that could be detrimental according to the investigator's judgment.
13. A known history of sensitivity to Gadolinium.
14. Inability to successfully undergo MRI scanning.
15. A known drug hypersensitivity to Mannitol.
16. Subjects who underwent endovascular treatment for Chronic Cerebrospinal Venous Insufficiency (CCSVI). |
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E.5 End points |
E.5.1 | Primary end point(s) |
Total number of confirmed relapses during the placebo-controlled treatment phase. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1. The cumulative number of new/enlarging T2 lesions taken at month 6 and month 12 (end of PC phase).
2. The cumulative number of enhancing lesions on T1-weighted images taken at months 6 and 12 (end of PC phase).
3. Brain atrophy as defined by the percent brain volume change from baseline to month 12 (end of PC phase). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
1.) Detection of ant-GA antibodies. 2.) Evaluation of PBL proliferation in response to GA. |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 110 |
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 | No |
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 |
Bulgaria |
Italy |
Croatia |
Romania |
Czech Republic |
Estonia |
Georgia |
Hungary |
Lithuania |
Israel |
Poland |
Russian Federation |
South Africa |
Ukraine |
United Kingdom |
United States |
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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
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Last visit of last subject. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |