Clinical trial NCT04121221: A Study to Asses Efficacy, Safety and Tolerability of Monthly Long-acting IM Injection of GA Depot in Subjects With RMS
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Multiple Sclerosis, Relapsing-Remitting
Keywords: Multiple Sclerosis
RMS
GA Depot
Multiple Sclerosis, Relapsing-Remitting
Lead sponsor: Mapi Pharma Ltd.
Sponsor class: INDUSTRY
First posted: 2019-10-09
Enrollment: 1016
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: During the placebo controlled period 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 for an additional 52 weeks, in which all subjects will receive 40mg of GA Depot IM once every 4 weeks.
Primary purpose: TREATMENT

Brief 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

Detailed 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.

Eligibility criteria: 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 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; 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.

Primary outcomes:
measure: Annualized Relapse Rate (ARR)
timeFrame: 52 weeks
Secondary outcomes:
measure: Changes in brain MRI (number of T1 lesions)
timeFrame: 52 weeks
measure: Changes in brain MRI (number of T2 lesions)
timeFrame: 52 weeks
measure: Hyperintense T2-lesion volume change
timeFrame: 52 weeks
measure: Enhancing T1-lesion volume change
timeFrame: 52 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Mapi Pharma Research site 08
state: Alabama
city: Cullman
country: United States
facility: Mapi Pharma Research site 11
state: Alabama
city: Pasadena
country: United States
facility: Mapi Pharma Research site 15
state: California
city: Denver
country: United States
facility: Mapi Pharma Research site 14
state: Colorado
city: Washington
country: United States
facility: Mapi Pharma Research site 12
state: District of Columbia
city: Homestead
country: United States
facility: Mapi Pharma Research site 17
state: Florida
city: Miami
country: United States
facility: Mapi Pharma Research site 09
state: Florida
city: Northbrook
country: United States
facility: Mapi Pharma Research site 01
state: Illinois
city: Detroit
country: United States
facility: Mapi Pharma Research site 02
state: Michigan
city: Westerville
country: United States
facility: Mapi Pharma Research site 13
state: Ohio
city: Round Rock
country: United States
facility: Mapi Pharma Research site 04
state: Texas
city: Gomel
country: Belarus
facility: Mapi Pharma Research site 02
city: Minsk
country: Belarus
facility: Mapi Pharma Research site 04
city: Minsk
country: Belarus
facility: Mapi Pharma Research site 05
city: Minsk
country: Belarus
facility: Mapi Pharma Research site 06
city: Vitebsk
country: Belarus
facility: Mapi Pharma Research site 01
city: Vitebsk
country: Belarus
facility: Mapi Pharma Research site 07
city: Banja Luka
country: Bosnia and Herzegovina
facility: Mapi Pharma Research site 04
city: Bihać
country: Bosnia and Herzegovina
facility: Mapi Pharma Research site 06
city: Sarajevo
country: Bosnia and Herzegovina
facility: Mapi Pharma Research site 01
city: Tuzla
country: Bosnia and Herzegovina
facility: Mapi Pharma Research site 03
city: Haskovo
country: Bulgaria
facility: Mapi Pharma Research site 14
city: Pazardzhik
country: Bulgaria
facility: Mapi Pharma Research site 10
city: Pleven
country: Bulgaria
facility: Mapi Pharma Research site 01
city: Pleven
country: Bulgaria
facility: Mapi Pharma Research site 02
city: Pleven
country: Bulgaria
facility: Mapi Pharma Research site 03
city: Pleven
country: Bulgaria
facility: Mapi Pharma Research site 07
city: Plovdiv
country: Bulgaria
facility: Mapi Pharma Research site 12
city: Rousse
country: Bulgaria
facility: Mapi Pharma Research site 18
city: Sofia
country: Bulgaria
facility: Mapi Pharma Research site 04
city: Sofia
country: Bulgaria
facility: Mapi Pharma Research site 05
city: Sofia
country: Bulgaria
facility: Mapi Pharma Research site 06
city: Sofia
country: Bulgaria
facility: Mapi Pharma Research site 08
city: Sofia
country: Bulgaria
facility: Mapi Pharma Research site 11
city: Sofia
country: Bulgaria
facility: Mapi Pharma Research site 13
city: Sofia
country: Bulgaria
facility: Mapi Pharma Research site 15
city: Sofia
country: Bulgaria
facility: Mapi Pharma Research site 16
city: Sofia
country: Bulgaria
facility: Mapi Pharma Research site 19
city: Veliko Tarnovo
country: Bulgaria
facility: Mapi Pharma Research site 09
city: Vratsa
country: Bulgaria
facility: Mapi Pharma Research site 17
city: Tallinn
country: Estonia
facility: Mapi Pharma Research site 01
city: Tbilisi
country: Georgia
facility: Mapi Pharma Research site 01
city: Tbilisi
country: Georgia
facility: Mapi Pharma Research site 02
city: Tbilisi
country: Georgia
facility: Mapi Pharma Research site 03
city: Tbilisi
country: Georgia
facility: Mapi Pharma Research site 04
city: Tbilisi
country: Georgia
facility: Mapi Pharma Research site 05
city: Tbilisi
country: Georgia
facility: Mapi Pharma Research site 06
city: Tbilisi
country: Georgia
facility: Mapi Pharma Research site 07
city: Tbilisi
country: Georgia
facility: Mapi Pharma Research site 08
city: Tbilisi
country: Georgia
facility: Mapi Pharma Research site 09
city: Safed
country: Israel
facility: Mapi Pharma Research site 01
city: Tel Aviv
country: Israel
facility: Mapi Pharma Research site 02
city: Chisinau
country: Moldova, Republic of
facility: Mapi Pharma Research site 01
city: Chisinau
country: Moldova, Republic of
facility: Mapi Pharma Research site 02
city: Barnaul
country: Russian Federation
facility: Mapi Pharma Research site 29
city: Bryansk
country: Russian Federation
facility: Mapi Pharma Research site 27
city: Chelyabinsk
country: Russian Federation
facility: Mapi Pharma Research site 23
city: Kazan
country: Russian Federation
facility: Mapi Pharma Research site 01
city: Kemerovo
country: Russian Federation
facility: Mapi Pharma Research site 19
city: Krasnodar
country: Russian Federation
facility: Mapi Pharma Research site 24
city: Moscow
country: Russian Federation
facility: Mapi Pharma Research site 03
city: Moscow
country: Russian Federation
facility: Mapi Pharma Research site 13
city: Moscow
country: Russian Federation
facility: Mapi Pharma Research site 14
city: Moscow
country: Russian Federation
facility: Mapi Pharma Research site 21
city: Moscow
country: Russian Federation
facility: Mapi Pharma Research site 25
city: Moscow
country: Russian Federation
facility: Mapi Pharma Research site 28
city: Nizhniy Novgorod
country: Russian Federation
facility: Mapi Pharma Research site 10
city: Nizhny Novgorod
country: Russian Federation
facility: Mapi Pharma Research site 02
city: Nizhny Novgorod
country: Russian Federation
facility: Mapi Pharma Research site 07
city: Novosibirsk
country: Russian Federation
facility: Mapi Pharma Research site 11
city: Perm
country: Russian Federation
facility: Mapi Pharma Research site 06
city: Pyatigorsk
country: Russian Federation
facility: Mapi Pharma Research site 22
city: Rostov-Na-Donu
country: Russian Federation
facility: Mapi Pharma Research site 08
city: Saint Petersburg
country: Russian Federation
facility: Mapi Pharma Research site 09
city: Saint Petersburg
country: Russian Federation
facility: Mapi Pharma Research site 18
city: Saint Petersburg
country: Russian Federation
facility: Mapi Pharma Research site 20
city: Samara
country: Russian Federation
facility: Mapi Pharma Research site 05
city: Saransk
country: Russian Federation
facility: Mapi Pharma Research site 26
city: Smolensk
country: Russian Federation
facility: Mapi Pharma Research site 15
city: Tyumen
country: Russian Federation
facility: Mapi Pharma Research site 16
city: Ufa
country: Russian Federation
facility: Mapi Pharma Research site 04
city: Ulyanovsk
country: Russian Federation
facility: Mapi Pharma Research site 17
city: Cherkasy
country: Ukraine
facility: Mapi Pharma Research site 32
city: Chernihiv
country: Ukraine
facility: Mapi Pharma Research site 06
city: Chernivtsi
country: Ukraine
facility: Mapi Pharma Research site 11
city: Dnipropetrovs'k
country: Ukraine
facility: Mapi Pharma Research site 03
city: Dnipropetrovs'k
country: Ukraine
facility: Mapi Pharma Research site 04
city: Dnipro
country: Ukraine
facility: Mapi Pharma Research site 24
city: Ivano-Frankivs'k
country: Ukraine
facility: Mapi Pharma Research site 18
city: Ivano-Frankivs'k
country: Ukraine
facility: Mapi Pharma Research site 26
city: Ivano-Frankivs'k
country: Ukraine
facility: Mapi Pharma Research site 27
city: Kharkiv
country: Ukraine
facility: Mapi Pharma Research site 09
city: Kharkiv
country: Ukraine
facility: Mapi Pharma Research site 10
city: Kherson
country: Ukraine
facility: Mapi Pharma Research site 08
city: Kyiv
country: Ukraine
facility: Mapi Pharma Research site 21
city: Kyiv
country: Ukraine
facility: Mapi Pharma Research site 25
city: Kyiv
country: Ukraine
facility: Mapi Pharma Research site 28
city: Kyiv
country: Ukraine
facility: Mapi Pharma Research site 29
city: Luts'k
country: Ukraine
facility: Mapi Pharma Research site 17
city: Lviv
country: Ukraine
facility: Mapi Pharma Research site 12
city: Lviv
country: Ukraine
facility: Mapi Pharma Research site 13
city: Lviv
country: Ukraine
facility: Mapi Pharma Research site 23
city: Odesa
country: Ukraine
facility: Mapi Pharma Research site 05
city: Poltava
country: Ukraine
facility: Mapi Pharma Research site 14
city: Ternopil'
country: Ukraine
facility: Mapi Pharma Research site 34
city: Vinnitsa
country: Ukraine
facility: Mapi Pharma Research site 16
city: Zaporizhzhya
country: Ukraine
facility: Mapi Pharma Research site 01
city: Zaporizhzhya
country: Ukraine
facility: Mapi Pharma Research site 02
city: Zaporizhzhya
country: Ukraine
facility: Mapi Pharma Research site 07
city: Zaporizhzhya
country: Ukraine
facility: Mapi Pharma Research site 20
city: Zhytomyr
country: Ukraine
facility: Mapi Pharma Research site 33
city: Úzhgorod
country: Ukraine
facility: Mapi Pharma Research site 31
Study officials:
affiliation: Mapi Pharma Ltd.
name: Laura Popper, MD
role: STUDY_DIRECTOR
affiliation: Mount Sinai School of Medicine, New York, US
name: Aaron E. Miller, Prof. MD
role: PRINCIPAL_INVESTIGATOR
References: