A multinational, multicenter, randomized, Phase III, double blind, parallel group, placebo controlled study in subjects with Relapsing forms of Multiple Sclerosis (RMS) to assess the efficacy, safety and tolerability of GA Depot, a long acting IM injection of glatiramer acetate, administered once every four weeks

Phase 1

Conditions: Relapsing forms of Multiple Sclerosis (RMS)
MedDRA version: 20.1Level: PTClassification code 10028245Term: Multiple sclerosisSystem Organ Class: 10029205 - Nervous system disorders
Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Registration Number: EUCTR2018-000284-93-EE

Lead Sponsor: Mapi Pharma Ltd.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 960

Inclusion Criteria

1. Adult subjects between 18-55 years of age, inclusive.
2. Subjects able to provide signed written informed consent.
3. Subjects must be willing and able to comply with the protocol requirements for the duration of the study.
4. MS diagnosis fulfilling the 2017 McDonald Criteria.
5. Subjects should be ambulatory with an EDSS score of 0-5.5 at screening and baseline visits. EDSS score will be determined by a separate, blinded trained EDSS rater.
6. Subjects should be relapse free and neurologically stable from one month before screening visit and from screening visit to baseline visit.
7. No systemic corticosteroid treatment or ACTH within one month prior to screening visit.
8. Subjects must have experienced at least one of the following:
i. One documented relapse in the 12 months prior to screening.
ii. Two documented relapses in the 24 months prior to screening.
iii. One documented relapse between 12 and 24 months prior to screening, with at least one documented T1-Gd enhancing lesion in MRI performed within 0-12 months before screening.
9. Women capable of child bearing must have a negative urine pregnancy test at screening visit and use an adequate contraceptive method throughout the study.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 960
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Use of experimental / investigational drug, and / or participation in drug clinical studies within the 6 months prior to screening.
2. Any off-label drug use for MS treatment such as high dose simvastatin and biotin within 6 months prior to screening.
3. Previous use of immunosuppressant including Mitoxantrone, Alemtuzumab, cladribine or any other cytotoxic agent.
4. Previous use of natalizumab or any anti-B cell agent within 9 months prior to screening.
5. Previous use of Fingolimod or Dimethyl Fumarate within 2 months prior to screening. Subjects will be excluded if they do not have a lymphocyte count of above 1,000/mm3 at screening.
6. Previous use of Teriflunomide within 12 months if no accelerated elimination procedure was used.
7. Previous treatment with immunomodulators (including IFNß 1a and 1b, and IV Immunoglobulin (IVIg) within 2 months prior to screening.
8. Previous use of GA or any other glatiramoid.
9. Chronic (more than 30 consecutive days) systemic (IV, PO or IM) corticosteroid treatment within 6 months prior to screening visit.
10. Previous total body irradiation or total lymphoid irradiation.
11. Previous stem-cell treatment, autologous bone marrow transplantation or allogeneic bone marrow transplantation.
12. Subjects with a clinically significant or unstable medical, psychiatric, or surgical conditions that would preclude safe and complete study participation, as determined by medical history, physical exams, ECG and/or abnormal laboratory tests. 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. Subjects who have >10 T1-Gd enhancing lesions at screening.
14. A known history of sensitivity to Gadolinium.
15. Inability to successfully undergo MRI scanning.
16. Pregnant or breast-feeding women.
17. Abnormal renal function (serum creatinine 1.5xULN or creatinine clearance <60 ml/min).
18. Abnormal liver function (transaminases >2xULN).
19. History of any anaphylactic reaction and/or serious allergic reaction following a vaccination, a proven hypersensitivity to any component of the study article (e.g., GA, Polyglactin, PVA).
20. A history of positive VDRL or positive testing for HIV, hepatitis, or tuberculosis.
21. Known or suspected history of drug or alcohol abuse.
22. Subjects diagnosed with any systemic autoimmune disease (other than MS) that may impact the CNS with MS like lesions such as Sarcoidosis, Sjögren's syndrome, Systemic Lupus Erythematosus (SLE), Lyme disease, Antiphospholipid antibodies (APLA) syndrome, etc. Subjects with stable local/organ autoimmune disease such as psoriasis, cutaneous lupus erythematosus, thyroiditis (Hashimoto's, Grave's) etc. may be considered eligible upon the investigator's discretion.
23. Any CNS disorder other than MS that may jeopardize the subject's participation in the study.
24. Subjects with uncontrolled diabetes.
25. Subjects with clotting disorders or receiving treatment with anticoagulants .

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the efficacy, safety and tolerability of GA Depot, a long acting IM injection of glatiramer acetate, administered once every four weeks, as compared to placebo in a study design of 52 weeks’ duration.<br>;Secondary Objective: To assess the long-term safety and tolerability of GA Depot, in subjects treated for up to 104 weeks.;Primary end point(s): Annualized Relapse Rate (ARR) during the 52 weeks of the PC period as derived from the total number of confirmed relapses. ;Timepoint(s) of evaluation of this end point: During the 52 weeks of the PC period

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1. Cumulative number of new enhancing lesions on T1-weighted images as compared to baseline. <br>2. Cumulative number of new or newly enlarging hyperintense T2 lesions as compared to baseline.<br>3. Change from baseline to Week 52 in hyperintense T2-lesion volume. <br>4. Change from baseline to Week 52 in enhancing T1-lesion volume.<br>;Timepoint(s) of evaluation of this end point: during the 52 weeks of the PC period

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