ClinicalTrials.gov
ClinicalTrials.gov Menu

Safety and Efficacy of Monthly Long-acting IM Injection of 40 mg GA Depot in Subjects With PPMS

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03362294
Recruitment Status : Recruiting
First Posted : December 5, 2017
Last Update Posted : November 26, 2018
Sponsor:
Information provided by (Responsible Party):
Mapi Pharma Ltd.

Brief Summary:

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 100 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.


Condition or disease Intervention/treatment Phase
Primary Progressive Multiple Sclerosis Drug: GA Depot 40mg once monthly Phase 2

Detailed Description:
  • 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 108 weeks, consisting of 4 weeks of screening evaluation (weeks -4 to 0), followed by a 100-week open-label treatment period, and a 4 weeks follow up period: through a total of 29 visits.
  • Vital signs and safety assessment will be performed at each visit during the study.
  • Physical examination will be performed at screening, baseline, 1 week after the second GA Depot treatment, 3 months after first GA Depot treatment and every 3 months thereafter. Last physical examination will be performed at FU visit.
  • MRI will be performed at screenings and every 6 months thereafter until the end of the treatment period .
  • Safety laboratory tests will be performed at screening, baseline, 1 month after first treatment, and every 3 months thereafter.
  • Neurological assessment will be performed at screening, baseline, 3 months, and then every 3 months until end of treatment.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Prospective, Multicenter, Single Arm, Open Label, Phase IIa Study to Assess the Safety and Efficacy of Once-a-month Long-acting Intramuscular Injection of 40mg Glatiramer Acetate (GA Depot) in Subjects With Primary Progressive Multiple Sclerosis (PPMS)
Actual Study Start Date : December 11, 2017
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: GA Depot 40mg once monthly
Monthly IM injection
Drug: GA Depot 40mg once monthly
Once-a-month long-acting intramuscular injection of 40mg Glatiramer Acetate (GA Depot)




Primary Outcome Measures :
  1. Safety (Adverse Events and Injection Site Reactions) [ Time Frame: 56 weeks ]
    Assessment of Adverse events (AEs) & Injection Sites Reactions (ISRs)


Secondary Outcome Measures :
  1. Efficacy (Confirmed Disease Progression) [ Time Frame: 100 weeks ]
    Time to onset of Confirmed Disease Progression (CDP) assessed by Expanded Disability Status Scale (EDSS). EDSS is a method of quantifying disability in people with MS. The EDSS scale ranges from 0 to 10 in 0.5 unit increments that represent higher levels of disability.

  2. Efficacy (Whole brain volume change) [ Time Frame: 100 weeks ]
    MRI assessment of percent of whole brain volume change.

  3. Efficacy (Cortical volume change) [ Time Frame: 100 weeks ]
    MRI assessment of percent of cortical volume change.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 65 years (inclusive).
  3. Subjects diagnosed with PPMS for at least 1 year and with signs of disease progression in the year prior to screening, in a rate of ≥ 1 point increase / year in the EDSS score for EDSS between 2-5 and a rate of ≥0.5 point increase / year in the EDSS scores > 5.
  4. EDSS ≥2 and ≤ 6.5 (Pyramidal or Cerebellar FS ≥ 2).
  5. Documented history or the presence at screening of > 1 oligoclonal band (OCB) if quantitative testing was done, or OCB+ if not quantitative testing done and/or positive IgG index in the cerebrospinal fluid (CSF).
  6. Women of child bearing potential must have a negative urine pregnancy test at screening and use an adequate contraceptive method throughout the study.
  7. Ability to provide written informed consent.

Exclusion Criteria:

  1. Subjects with RRMS, SPMS, or PRMS.
  2. Subjects with a documented history of clinical 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03362294


Locations
Israel
Barzilai MC Recruiting
Ashkelon, Israel
Contact: Nir Michal    08-6745036    nirm@bmc.gov.il   
Principal Investigator: Ron Milo, MD         
Assaf Harofeh MC Recruiting
Be'er Ya'aqov, Israel
Contact: Shlomo Flecther, MD    08-9779879    shlomofl@asaf.health.gov.il   
Principal Investigator: Shlomo Flecther, MD         
Bnai Zion MC Recruiting
Haifa, Israel
Contact: Luda Mazarib    052-2794800    luda.mazarib@b-zion.org.il   
Principal Investigator: Boaz Weller, MD         
Wolfson MC Withdrawn
Holon, Israel
Kaplan MC Recruiting
Reẖovot, Israel
Contact: Ayelet Sherman    08-9441051 ext 2051    AyeletGo@clalit.org.il   
Principal Investigator: Ronit Gilad, Prof.         
Tel Aviv Sourasky MC Recruiting
Tel Aviv, Israel
Contact: Irina Komarov    03-6974380    irinako@tlvmc.gov.il   
Principal Investigator: Arnon Karni, MD         
Sponsors and Collaborators
Mapi Pharma Ltd.
Investigators
Principal Investigator: Arnon Karni, MD Coordinating PI

Responsible Party: Mapi Pharma Ltd.
ClinicalTrials.gov Identifier: NCT03362294     History of Changes
Other Study ID Numbers: PPMS-GA Depot 002
First Posted: December 5, 2017    Key Record Dates
Last Update Posted: November 26, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Sclerosis
Multiple Sclerosis
Multiple Sclerosis, Chronic Progressive
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Glatiramer Acetate
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Immunosuppressive Agents
Antirheumatic Agents