A Study to Asses Efficacy, Safety and Tolerability of Monthly Long-acting IM Injection of GA Depot in Subjects With RMS

Overview

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

Full Title of Study: “A Phase III Study in Subjects With Relapsing Forms of Multiple Sclerosis (RMS) to Asses Efficacy, Safety and Tolerability of GA Depot, a Long Acting IM Injection of Glatiramer Acetate, Once Monthly Compared to Placebo”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Factorial Assignment
    • Primary Purpose: Treatment
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: December 2021

Detailed Description

A total of 960 subjects are planned to be randomized into this study to receive treatment with GA Depot or with matching placebo.

During the placebo controlled period (PC period, the first 52 weeks of the study immediately after randomization) subjects will receive either 40mg of GA Depot or matching placebo, IM, once every 4 weeks, for a total of 13 times.

Subjects who complete the PC period of the study will be offered to continue into the open label period (OL period) for an additional 52 weeks, in which all subjects will receive 40mg of GA Depot IM once every 4 weeks.

Interventions

  • Drug: GA Depot
    • IM injection once every 4 weeks
  • Other: Placebo
    • IM injection once every 4 weeks

Arms, Groups and Cohorts

  • Experimental: GA Depot
    • Monthly IM injection
  • Placebo Comparator: Placebo
    • Monthly IM injection

Clinical Trial Outcome Measures

Primary Measures

  • Annualized Relapse Rate (ARR)
    • Time Frame: 52 weeks
    • Annualized Relapse Rate (ARR) will be derived from the total number of confirmed relapses.

Secondary Measures

  • Changes in brain MRI (number of T1 lesions)
    • Time Frame: 52 weeks
    • Cumulative number of new enhancing lesions on T1-weighted images as compared to baseline.
  • Changes in brain MRI (number of T2 lesions)
    • Time Frame: 52 weeks
    • Cumulative number of new or newly enlarging hyperintense T2 lesions as compared to baseline.
  • Hyperintense T2-lesion volume change
    • Time Frame: 52 weeks
    • Change from baseline to Week 52 in hyperintense T2-lesion volume.
  • Enhancing T1-lesion volume change
    • Time Frame: 52 weeks
    • Change from baseline to Week 52 in enhancing T1-lesion volume.

Participating in This Clinical Trial

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.

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 IFNβ 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.

18. Abnormal liver function.

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.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 55 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Mapi Pharma Ltd.
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Laura Popper, MD, Study Director, Mapi Pharma Ltd.
    • Aaron E. Miller, Prof. MD, Principal Investigator, Mount Sinai School of Medicine, New York, US
  • Overall Contact(s)
    • Laura Popper, MD, +972-737121213, GAD3@mapi-pharma.com

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