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 | 19.1 |
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 number of new T2 lesions at month 12 (end of placebo-controlled phase) as compared to the baseline scan.
- 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. |
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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. |
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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 | 20 |
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 |
Croatia |
Czech Republic |
Estonia |
Georgia |
Hungary |
Israel |
Italy |
Lithuania |
Poland |
Romania |
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 | 3 |
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 | 3 |
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 |