An Efficacy, Safety and Tolerability Study of Glatiramer Acetate (GA) 20 mg/0.5 ml New Formulation Administered Daily by Subcutaneous (SC) Injection in Subjects With Relapsing-Remitting Multiple Sclerosis (RRMS)

Study Overview
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Brief Summary
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This study will investigate the efficacy, safety and tolerability of a new formulation of glatiramer acetate administered at 20 mg/0.5 ml daily versus placebo in patients with Relapsing-Remitting Multiple Sclerosis (RRMS).

Detailed Description
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Approximately 1400 participants were planned for this study, however only 178 were enrolled prior to early termination.

Official Title
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A Multinational, Multicenter, Randomized, Parallel Group, Double Blind, Placebo Controlled Study Performed in Subjects With Relapsing-Remitting Multiple Sclerosis to Assess the Efficacy, Safety and Tolerability of Glatiramer Acetate 20mg/0.5ml New Formulation Administered Daily by Subcutaneous Injection

Conditions
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Relapsing-Remitting Multiple Sclerosis

Intervention / Treatment
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* Drug: Glatiramer Acetate
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must meet all inclusion criteria in order to be eligible for the study: Subjects must have a confirmed and documented multiple sclerosis (MS) diagnosis as defined by the 2010 Revised McDonald criteria [Ann Neurol 2011: 69:292-302], with a relapsing-remitting disease course. Subjects must be ambulatory with a Kurtzke's Expanded Disability Status Scale (EDSS) score of 0-5.5 in both screening and baseline visits. Subjects must be in a relapse-free, stable neurological condition and free of corticosteroid treatment [intravenous (IV), intramuscular (IM) and/or by mouth (PO)] or ACTH (adrenocorticotropic hormone) 30 days prior to screening (Month-1) and between screening and baseline (Month 0) visits. Subjects must have experienced one of the following: At least one documented relapse in the 12 months prior to screening, At least two documented relapses in the 24 months prior to screening, One documented relapse between 12 and 24 months prior to screening with at least one documented T1-Gd enhancing lesion in a magnetic resonance imaging (MRI) performed within 12 months prior to screening. Subjects must be between 18 and 55 years of age, inclusive. 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)]. Subjects must be able to sign and date a written informed consent prior to entering the study. Subjects must be willing and able to comply with the protocol requirements for the duration of the study. Exclusion Criteria: Any of the following conditions will exclude the subject from entering the study: Subjects with progressive forms of MS. Use of experimental or investigational drugs, and/or participation in drug clinical studies within the 6 months prior to screening. Use of immunosuppressive agents (including Mitoxantrone and Fingolimod) or cytotoxic agents within 6 months prior to the screening visit. Use of natalizumab (Tysabri®) or any other monoclonal antibodies within 2 years prior to screening. Use of cladribine within 2 years prior to screening. Previous treatment with immunomodulators [including IFNβ 1a and 1b, and IV Immunoglobulin (IVIg)] within 2 months prior to screening. Previous use of glatiramer acetate (GA) or any other glatiramoid. Chronic (more than 30 consecutive days) systemic (IV, PO or IM) corticosteroid treatment within 6 months prior to screening visit. Previous total body irradiation or total lymphoid irradiation. Previous stem-cell treatment, autologous bone marrow transplantation or allogenic bone marrow transplantation. Pregnancy or breastfeeding. 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. A known history of sensitivity to Gadolinium. Glomerular filtration rate (GFR) ≤ 60 mL/minute at the screening visit Inability to successfully undergo MRI scanning. A known drug hypersensitivity to Mannitol. Subjects who underwent endovascular treatment for chronic cerebrospinal venous insufficiency (CCSVI).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Glatiramer Acetate<br>Glatiramer acetate (GA) 20 mg/0.5 ml solution in prefilled syringe for subcutaneous injection once daily. | Drug: Glatiramer Acetate<br>* Glatiramer acetate 20mg in 0.5ml for subcutaneous injection in a pre-filled syringe (PFS) is administered daily. Each PFS also contains 20mg mannitol dissolved in water for injection.<br>* Other names: Copaxone®;|
| Placebo Comparator: Placebo<br>Placebo solution in prefilled syringe for subcutaneous injection once daily. | Drug: Placebo<br>* Matching placebo injection; 20 mg mannitol dissolved in 0.5 mL water for subcutaneous injection in a PFS is administered daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Annualized Relapse Rate During the Placebo Controlled Period | The total number of confirmed relapses during the placebo-controlled phase is divided by the sum of the number of days on study in the placebo-controlled phase and then multiplied by the number of days in the year to calculate the annualized relapse rate. | Day 1 up to Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Cumulative Number of New or Enlarging T2 Lesions Measured at Months 6 and 12 (End of Placebo Controlled Period) | Inflammatory disease activity was assessed by magnetic resonance imaging (MRI) measurement of the number of new or newly enlarged T2 lesions. | Day 1 up to Month 12 | 
| The Cumulative Number of Gadolinium-enhancing Lesions on T1-weighted Images Measured at Months 6 and 12 (End of Placebo Controlled Period) | Inflammatory disease activity was assessed by magnetic resonance imaging (MRI) measurement of the number of gadolinium-enhanced T1 lesions. | Day 1 up to Month 12 | 
| Percent Change From Baseline to Month 12 (End of Placebo Controlled Period) in Brain Volume | Brain atrophy was defined by the percent brain volume change from baseline to Month 12 | Day 1 up to Month 12 |