This is a phase IIa study with GA Depot in subjects with Primary Progressive MS. GA Depot will be administered intramuscularly (IM), once every four weeks for 52 weeks.

The purpose of this study is to assess the safety and efficacy of GA Depot to slow the accumulation of disability progression in subjects with Primary Progressive MS.

• 12 to 24 Subjects with a diagnosis of primary progressive multiple sclerosis (PPMS) who are not treated for PPMS at study entry (except for symptoms relief).
• Study product is GA long-acting injection (GA Depot) which is a combination of extended-release microspheres for injection and diluent (water for injection) for parenteral use. GA Depot will be administered intramuscularly (IM).
• The study duration for an individual subject in the core study will be 60 weeks, consisting of 4 weeks of screening evaluation (weeks -4 to 0), followed by a 52-week open-label treatment period, and a 4 weeks follow up period: through a total of 17 visits.
• Vital signs and safety assessment will be performed at each visit during the study.
• Physical examination will be performed at screening, baseline, weeks 5, 12, 24, 36, 52 (end of study) and follow up visit.
• MRI will be performed at screenings, week 24 and week 52 (end of study).
• Safety laboratory tests will be performed at screening visit, baseline, weeks 4, 12, 24, 36 and 52 (end of study).
• Neurological assessment will be performed at screening visit, baseline, weeks 12, 24, 36 and 52 (end of study).

Inclusion Criteria:

1. Male or female subjects diagnosed with PPMS; Diagnosis of PPMS consistent with the McDonald Criteria (revisions of 2010).
2. Age between 18 and 55 years.
3. Subjects diagnosed with PPMS for at least 1 year and a sustained increment of ≥ 1 point in the EDSS score in the last year prior to screening.
4. EDSS ≥2 and ≤ 5.5.
5. Documented history or the presence at screening of > 1 oligoclonal band (OCB) (IgG OCB positive (OCGB+)) and/or positive IgG index in the cerebrospinal fluid (CSF).
6. Subjects with at least 1 gadolinium-enhancing lesion on baseline MRI and/or documented in previous MRI within 12 months prior to screening visit.
7. Women of child bearing potential must have a negative urine pregnancy test at screening and use an adequate contraceptive method throughout the study.
8. Ability to provide written informed consent.

Exclusion Criteria:

1. Subjects with RRMS, SPMS, or PRMS.
2. Subjects with a documented history of relapse events.
3. Any relevant medical, surgical, or psychiatric condition, laboratory value, or concomitant medication which, in the opinion of the investigator, makes the subject unsuitable for study entry or potentially unable to complete all aspects of the study.
4. Contraindications or inability to successfully undergo magnetic resonance imaging (MRI) scanning.
5. Subjects diagnosed with any other than MS systemic autoimmune disease that may impact the CNS with MS like lesions such as Sarcoidosis, Sjögren's syndrome, Systemic Lupus Erythematosus (SLE), Lyme disease, APLA syndrome, etc.. Subjects with stable local/organ autoimmune disease such as psoriasis, Cutaneous Lupus erythematosus, thyroiditis (Hashimoto, grave) etc. may be considered eligible upon the PI's discretion.
6. Severe anemia (hemoglobin <10 g/dL).
7. Abnormal renal function (serum creatinine >1.5xULN or creatinine clearance <30 ml/min).
8. Abnormal liver function (transaminases >2xULN).
9. Pregnant or breast-feeding women.
10. Treatment with any kind of steroids during the last month prior to screening visit.
11. History of any anaphylactic reaction and/or serious allergic reaction following a vaccination, a known hypersensitivity to any component of the study drug, e.g. glatiramer acetate (GA), polylactic-co-glycolic acid (PLGA), polyvinyl alcohol (PVA).
12. Known or suspected history of drug or alcohol abuse.
13. Known as positive for HIV, hepatitis, VDRL, or tuberculosis.
14. Active malignant disease of any kind. However, a patient, who had a malignant disease in the past, was treated and is currently disease - free for at least 7 years, may be considered eligible, upon the PI and sponsor's discretion.
15. Previous treatment with B-cell-targeting therapies (e.g. rituximab, ocrelizumab, atacicept, belimumab or ofatumumab) within 6 months prior to screening visit.
16. Previous treatment with cladribine within 2 years prior to screening visit
17. Previous treatment with azathioprine, mitoxantrone or methotrexate within 6 months prior to screening visit.
18. Previous treatment with lymphocyte-trafficking modifiers (e.g. natalizumab, fingolimod) within 6 months prior to screening visit. Subjects should have a total lymphocyte count within normal range.
19. Previous treatment with beta interferons, intravenous immunoglobulin, plasmapheresis within 2 months prior to screening visit.
20. Previous treatment with any glatiramer acetate therapy within 3 months prior to screening visit.
21. Uncontrolled diabetes.
22. Participation in an investigational study drug within 30 days prior to study entry.