Efficacy and Safety of GTR in Comparison to Copaxone®

GTR is being developed by Synthon as a similar version of Copaxone®. GTR has a similar quantitative and qualitative composition as Copaxone®, with regard to active substance and excipients and is presented in the same dosage form (pre-filled syringe containing a solution for injection). Introduction of GTR is anticipated to have a price lowering effect and will give doctors and patients more choice in the pharmaceutical armamentarium for MS.

This trial consists of two parts:

Part 1 is a multi-country, multi-centre, randomized, double-blind, active and placebo-controlled, equivalence trial comparing the efficacy and safety and tolerability of GTR versus Copaxone® in subjects with RRMS. Eligible subjects will be randomly assigned to receive daily 20 mg GTR (Synthon BV), 20 mg Copaxone® (TEVA) or placebo for a period of 9 months.

In Part 2, the trial continues as an open-label uncontrolled trial to evaluate efficacy and safety of long-term treatment with GTR. Subjects completing the 9-month double-blind period will be treated with open-label 20 mg daily GTR for another 15 months.

Inclusion criteria

• Willing and able to sign written Informed Consent;
• Female and male subjects aged 18-55 years inclusive at the time of Informed Consent signing;
• Diagnosis of RRMS according to the revised McDonald criteria;
• Expanded Disability Status Scale (EDSS) score of 0.0 up to and including 5.5;
• Neurologically stable with no evidence of relapse within 30 days prior to randomization;
• Experienced at least 1 relapse in the year before first screening assessment;
• 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;
• 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 immuno-modulatory treatment, or a screening MRI showing maximally 15 T1-GdE lesions;
• 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;
• Female subjects of childbearing potential must agree to practice appropriate contraceptive methods as assessed by the investigator.

Exclusion criteria

• Any life-threatening, medically unstable or otherwise clinically significant condition or findings other than MS, in particular neoplastic disease, seizure disorders, or psychiatric disease;
• Any clinically significant deviation from reference ranges in laboratory tests;
• Positive laboratory test results for human immunodeficiency virus (HIV), HBsAg or HCV at screening;
• Any significant deviation from reference ranges for hepatic function;
• 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);
• Having been treated with or having received

• 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
• within one year before screening:

• mitoxantrone, but subject cannot be enrolled when mitoxantrone was taken at a cumulative lifetime dosing above 100 mg/m2
• 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)
• within 3 months before screening:

• azathioprine, methotrexate
• plasma exchange
• any other experimental intervention, in particular experimental drugs
• within 1 month before screening:

• Interferon-β 1a or 1b
• short-term oral or injectable corticosteroids for treatment of a relapse
• short-term ACTH
• 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);
• Pregnancy or breastfeeding;
• Known hypersensitivity to gadolinium-containing products, glatiramer acetate or mannitol;
• Having an estimated glomerular filtration rate (eGFR) < 50 mL/min/1.73m2;
• 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;
• Any reason why, in the investigator's opinion, the subject should not participate.