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

Multiple Sclerosis, Relapsing-Remitting Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04121221
• Other study ID #: Mapi GA Depot Phase III - 001
• Status: Completed
• Phase: Phase 3
• Start date: September 19, 2019
• Est. completion date: June 13, 2023

Study information

• Verified date: November 2023
• Source: Mapi Pharma Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

A total of 1000 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1016
• Est. completion date: June 13, 2023
• Est. primary completion date: June 13, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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. At least one documented relapse in the 12 months prior to screening. ii. At least 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 and baseline 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 within 5 years.

4. Previous use of Natalizumab or any anti-B cell agent within 9 months prior to screening.

5. Previous use of Fingolimod or any other sphingosine-1-phosphate receptor modulator, Dimethyl Fumarate, Diroximel Fumarate (DRF), or Monomethyl 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; and or subjects with an increased risk of serious Covid-19 related morbidity. 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. Positive testing or a history of positive testing for syphilis, 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.

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Relapsing-Remitting
• Sclerosis

Intervention

Drug:
• GA Depot
Long acting intramuscular injection of glatiramer acetate, once every 4 weeks

Other:
• Placebo
IM injection once every 4 weeks

Locations

Country	Name	City	State
Belarus	Mapi Pharma Research site 02	Gomel
Belarus	Mapi Pharma Research site 04	Minsk
Belarus	Mapi Pharma Research site 05	Minsk
Belarus	Mapi Pharma Research site 06	Minsk
Belarus	Mapi Pharma Research site 01	Vitebsk
Belarus	Mapi Pharma Research site 07	Vitebsk
Bosnia and Herzegovina	Mapi Pharma Research site 04	Banja Luka
Bosnia and Herzegovina	Mapi Pharma Research site 06	Bihac
Bosnia and Herzegovina	Mapi Pharma Research site 01	Sarajevo
Bosnia and Herzegovina	Mapi Pharma Research site 03	Tuzla
Bulgaria	Mapi Pharma Research site 14	Haskovo
Bulgaria	Mapi Pharma Research site 10	Pazardzhik
Bulgaria	Mapi Pharma Research site 01	Pleven
Bulgaria	Mapi Pharma Research site 02	Pleven
Bulgaria	Mapi Pharma Research site 03	Pleven
Bulgaria	Mapi Pharma Research site 07	Pleven
Bulgaria	Mapi Pharma Research site 12	Plovdiv
Bulgaria	Mapi Pharma Research site 18	Rousse
Bulgaria	Mapi Pharma Research site 04	Sofia
Bulgaria	Mapi Pharma Research site 05	Sofia
Bulgaria	Mapi Pharma Research site 06	Sofia
Bulgaria	Mapi Pharma Research site 08	Sofia
Bulgaria	Mapi Pharma Research site 11	Sofia
Bulgaria	Mapi Pharma Research site 13	Sofia
Bulgaria	Mapi Pharma Research site 15	Sofia
Bulgaria	Mapi Pharma Research site 16	Sofia
Bulgaria	Mapi Pharma Research site 19	Sofia
Bulgaria	Mapi Pharma Research site 09	Veliko Tarnovo
Bulgaria	Mapi Pharma Research site 17	Vratsa
Estonia	Mapi Pharma Research site 01	Tallinn
Georgia	Mapi Pharma Research site 01	Tbilisi
Georgia	Mapi Pharma Research site 02	Tbilisi
Georgia	Mapi Pharma Research site 03	Tbilisi
Georgia	Mapi Pharma Research site 04	Tbilisi
Georgia	Mapi Pharma Research site 05	Tbilisi
Georgia	Mapi Pharma Research site 06	Tbilisi
Georgia	Mapi Pharma Research site 07	Tbilisi
Georgia	Mapi Pharma Research site 08	Tbilisi
Georgia	Mapi Pharma Research site 09	Tbilisi
Israel	Mapi Pharma Research site 01	Safed
Israel	Mapi Pharma Research site 02	Tel Aviv
Moldova, Republic of	Mapi Pharma Research site 01	Chisinau
Moldova, Republic of	Mapi Pharma Research site 02	Chisinau
Russian Federation	Mapi Pharma Research site 29	Barnaul
Russian Federation	Mapi Pharma Research site 27	Bryansk
Russian Federation	Mapi Pharma Research site 23	Chelyabinsk
Russian Federation	Mapi Pharma Research site 01	Kazan
Russian Federation	Mapi Pharma Research site 19	Kemerovo
Russian Federation	Mapi Pharma Research site 24	Krasnodar
Russian Federation	Mapi Pharma Research site 03	Moscow
Russian Federation	Mapi Pharma Research site 13	Moscow
Russian Federation	Mapi Pharma Research site 14	Moscow
Russian Federation	Mapi Pharma Research site 21	Moscow
Russian Federation	Mapi Pharma Research site 25	Moscow
Russian Federation	Mapi Pharma Research site 28	Moscow
Russian Federation	Mapi Pharma Research site 10	Nizhniy Novgorod
Russian Federation	Mapi Pharma Research site 02	Nizhny Novgorod
Russian Federation	Mapi Pharma Research site 07	Nizhny Novgorod
Russian Federation	Mapi Pharma Research site 11	Novosibirsk
Russian Federation	Mapi Pharma Research site 06	Perm
Russian Federation	Mapi Pharma Research site 22	Pyatigorsk
Russian Federation	Mapi Pharma Research site 08	Rostov-Na-Donu
Russian Federation	Mapi Pharma Research site 09	Saint Petersburg
Russian Federation	Mapi Pharma Research site 18	Saint Petersburg
Russian Federation	Mapi Pharma Research site 20	Saint Petersburg
Russian Federation	Mapi Pharma Research site 05	Samara
Russian Federation	Mapi Pharma Research site 26	Saransk
Russian Federation	Mapi Pharma Research site 15	Smolensk
Russian Federation	Mapi Pharma Research site 16	Tyumen
Russian Federation	Mapi Pharma Research site 04	Ufa
Russian Federation	Mapi Pharma Research site 17	Ulyanovsk
Ukraine	Mapi Pharma Research site 32	Cherkasy
Ukraine	Mapi Pharma Research site 06	Chernihiv
Ukraine	Mapi Pharma Research site 11	Chernivtsi
Ukraine	Mapi Pharma Research site 24	Dnipro
Ukraine	Mapi Pharma Research site 03	Dnipropetrovs'k
Ukraine	Mapi Pharma Research site 04	Dnipropetrovs'k
Ukraine	Mapi Pharma Research site 18	Ivano-Frankivs'k
Ukraine	Mapi Pharma Research site 26	Ivano-Frankivs'k
Ukraine	Mapi Pharma Research site 27	Ivano-Frankivs'k
Ukraine	Mapi Pharma Research site 09	Kharkiv
Ukraine	Mapi Pharma Research site 10	Kharkiv
Ukraine	Mapi Pharma Research site 08	Kherson
Ukraine	Mapi Pharma Research site 21	Kyiv
Ukraine	Mapi Pharma Research site 25	Kyiv
Ukraine	Mapi Pharma Research site 28	Kyiv
Ukraine	Mapi Pharma Research site 29	Kyiv
Ukraine	Mapi Pharma Research site 17	Luts'k
Ukraine	Mapi Pharma Research site 12	Lviv
Ukraine	Mapi Pharma Research site 13	Lviv
Ukraine	Mapi Pharma Research site 23	Lviv
Ukraine	Mapi Pharma Research site 05	Odesa
Ukraine	Mapi Pharma Research site 14	Poltava
Ukraine	Mapi Pharma Research site 34	Ternopil'
Ukraine	Mapi Pharma Research site 31	Úzhgorod
Ukraine	Mapi Pharma Research site 16	Vinnitsa
Ukraine	Mapi Pharma Research site 01	Zaporizhzhya
Ukraine	Mapi Pharma Research site 02	Zaporizhzhya
Ukraine	Mapi Pharma Research site 07	Zaporizhzhya
Ukraine	Mapi Pharma Research site 20	Zaporizhzhya
Ukraine	Mapi Pharma Research site 33	Zhytomyr
United States	Mapi Pharma Research site 08	Birmingham	Alabama
United States	Mapi Pharma Research site 11	Cullman	Alabama
United States	Mapi Pharma Research site 14	Denver	Colorado
United States	Mapi Pharma Research site 02	Detroit	Michigan
United States	Mapi Pharma Research site 17	Homestead	Florida
United States	Mapi Pharma Research site 09	Miami	Florida
United States	Mapi Pharma Research site 01	Northbrook	Illinois
United States	Mapi Pharma Research site 15	Pasadena	California
United States	Mapi Pharma Research site 04	Round Rock	Texas
United States	Mapi Pharma Research site 12	Washington	District of Columbia
United States	Mapi Pharma Research site 13	Westerville	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Mapi Pharma Ltd.

Countries where clinical trial is conducted

United States,  Belarus,  Bosnia and Herzegovina,  Bulgaria,  Estonia,  Georgia,  Israel,  Moldova, Republic of,  Russian Federation,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Annualized Relapse Rate (ARR)	Annualized Relapse Rate (ARR) will be derived from the total number of confirmed relapses.	52 weeks
Secondary	Changes in brain MRI (number of T1 lesions)	Cumulative number of new enhancing lesions on T1-weighted images as compared to baseline.	52 weeks
Secondary	Changes in brain MRI (number of T2 lesions)	Cumulative number of new or newly enlarging hyperintense T2 lesions as compared to baseline.	52 weeks
Secondary	Hyperintense T2-lesion volume change	Change from baseline to Week 52 in hyperintense T2-lesion volume.	52 weeks
Secondary	Enhancing T1-lesion volume change	Change from baseline to Week 52 in enhancing T1-lesion volume.	52 weeks