E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsing-remitting Multiple sclerosis (RRMS) |
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E.1.1.1 | Medical condition in easily understood language |
Relapsing-remitting multiple sclerosis is a form of multiple sclerosis. Patients tend to experience an attack or series of attacks (relapse), followed by complete or partial recovery (remission). |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
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 |
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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 effect of Glatiramer Acetate (GA) injection 20 mg/0.5 ml administered daily compared to placebo in subjects with RRMS on the total number of confirmed relapses during the 12 month PC phase. This will be used to calculate the Annualized Relapse Rate during the PC phase per each arm. |
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E.2.2 | Secondary objectives of the trial |
To assess the effect of GA injection 20 mg/0.5ml administered daily compared to placebo in subjects with RRMS: - on the cumulative number of new/enlarging T2 lesions measured at Months 6 and 12 (end of PC phase). - on the cumulative number of Gd-enhancing lesions on T1-weighted images measured at Months 6 and 12 (end of PC phase). - on the development of brain atrophy as defined by the percent brain volume change from baseline to Month 12 (end of PC 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 |
•Blood samples for Pharmacogenetic (PGx) analysis will be collected from all subjects who signed the appropriate informed consent form, pending Ethic Committees approval, during the PC phase, preferably at Month 0 (baseline) or any other visit following Month 0. |
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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, 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 or ACTH, 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. 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 (including Mitoxantrone and Fingolimod) or cytotoxic agents within 6 months prior to the screening visit. 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 within 2 months prior to screening. 7. Previous use of GA or any other glatiramoid. 8. Chronic systemic 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. GFR ≤ 60 mL/min/ 1.73m2 at the screening visit 15. Inability to successfully undergo MRI scanning. 16. A known drug hypersensitivity to Mannitol. 17. 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) |
The total number of confirmed relapses during the 12 months PC phase. This will be used to calculate the Annual Relapse Rate during the PC phase per each arm. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Relapses will be confirmed/monitored throughout the study. |
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E.5.2 | Secondary end point(s) |
- cumulative number of new/enlarging T2 lesions measured at Months 6 and 12 (End of the PC phase) - cumulative number of Gd-enhancing lesions on T1-weighted images measured at Month - 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 |
Following GFR evaluation, all subjects will undergo MRI scans at months 0 (13-7 days prior to baseline visit), Month 6 and Month 12 (end of PC phase) or ET. During an unscheduled visit the investigator will decide if an MRI scan is required. - The cumulative number of new/enlarging T2 lesions measured at Months 6 and 12 (end of PC phase). - The cumulative number of Gd-enhancing lesions on T1-weighted images measured at Months 6 and 12 (End of the PC phase). -The percent brain volume change from baseline to Month 12 (end of PC phase). |
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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 | No |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 84 |
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 |
Albania |
Belarus |
Bosnia and Herzegovina |
Bulgaria |
Croatia |
Czech Republic |
Estonia |
Georgia |
Germany |
Hungary |
Latvia |
Lithuania |
Macedonia, the former Yugoslav Republic of |
Mexico |
Moldova, Republic of |
Montenegro |
Poland |
Romania |
Russian Federation |
Serbia |
Ukraine |
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. Open Label (OL) Extension: Subjects completing the PC phase or subjects that experienced two confirmed MS relapses during the PC phase will be offered the opportunity to enter into an OL extension phase, in which all subjects will be treated with GA 20 mg/0.5 ml administered daily by SC injection for additional 24 months or until the development of this formulation is stopped by the Sponsor (whichever is sooner). |
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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 | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |