A Study in Subjects With Relapsing-Remitting Multiple Sclerosis (RRMS) to Assess the Efficacy, Safety and Tolerability of Glatiramer Acetate (GA) Injection 40 mg Administered Three Times a Week Compared to Placebo

A Multinational, Multicenter, Randomized, Parallel-group Study Performed in Subjects With Relapsing-Remitting Multiple Sclerosis (RRMS) to Assess the Efficacy, Safety and Tolerability of Glatiramer Acetate (GA) Injection 40 mg Administered Three Times a Week Compared to Placebo in a Double-blind Design

Sponsors

Lead Sponsor: Teva Pharmaceutical Industries, Ltd.

Source Teva Pharmaceutical Industries
Brief Summary

The study is designed to assess the efficacy of Glatiramer Acetate (GA) injection 40 mg administered three times a week compared to placebo in subjects with RRMS, as measured by the number of confirmed relapses during the 12 month placebo controlled period. The study has two periods:

- Placebo Controlled Period: 12 months of 40 mg administered three times a week by subcutaneous injection or matching placebo.

- Open Label Extension Period: All subjects will continue treatment with GA 40 mg administered three times a week, until this dose strength is commercially available for the treatment of relapsing remitting multiple sclerosis (RRMS) patients or until the development of this GA dose regimen is stopped by the Sponsor

Detailed Description

Participants who were randomized to the GA 40 mg treatment arm in the Double-Blind Period, continue that treatment in the Open-Label Extension Period and are referred to as "Early Start" participants. Participants randomized to the Placebo arm in the Double-Blind Period and switched to GA 40 mg subcutaneous injections three times a week in the Open-Label Extension are referred to as "Delayed Start" participants.

Overall Status Completed
Start Date June 22, 2010
Completion Date May 12, 2017
Primary Completion Date May 8, 2012
Phase Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
Total Number of Confirmed Relapses During the Placebo Controlled (PC) Treatment Period Estimated by Negative Binomial Regression Day 1 to 12 months
Annualized Rate of Confirmed Relapses Comparing Early Starters to Delayed Starters Estimated by Negative Binomial Regression Day 1 up to 6.5 years
Secondary Outcome
Measure Time Frame
The Cumulative Number of New/Enlarging T2 Lesions Taken at Month 6 and Month 12 During the Placebo Controlled (PC) Treatment Period Estimated by Negative Binomial Regression Baseline (Day -7), Month 6, Month 12
The Cumulative Number of Gadolinium (Gd)-Enhanced Lesions on T1-Weighted Images At Month 6 and Month 12 of the Placebo-Controlled (PC) Treatment Period Estimated by Negative Binomial Regression Baseline (Day -7), Month 6, Month 12
Brain Atrophy As Defined by the Percent of Change in Normalized Brain Volume From Baseline to Month 12 During the Placebo Controlled (PC) Treatment Period Baseline (Day -7), Month 12
The Number of New/Enlarging T2 Lesions at Months 6, 12 and 36 Estimated by Negative Binomial Regression Baseline (Day -7), Month 6, Month 12, Month 36
The Cumulative Number of Gadolinium (Gd)-Enhanced Lesions on T1-Weighted Images At Months 6, 12 and 36 Estimated by Negative Binomial Regression Baseline (Day -7), Month 6, Month 12, Month 36
Brain Atrophy As Defined by the Percent of Change in Brain Volume From Baseline to Months 6, 12 and 36 Estimated by a Mixed Model for Repeated Measures Baseline (Day -7), Month 6, Month 12, Month 36
Participants With Treatment-Emergent Adverse Events (TEAEs) Early Start: Day 1 up to 6.5 years Delayed Start - Placebo: Day 1 up to Month 12 Delayed Start - GA: Month 13 up to 6.5 years
Enrollment 1404
Condition
Intervention

Intervention Type: Drug

Intervention Name: Glatiramer acetate (GA)

Description: GA 40 mg/mL administered 3 times a week by subcutaneous injection for a period of 12 months for participants assigned to GA treatment in the Double-Blind Period, and GA 40 mg/mL administered 3 times a week by subcutaneous injection for all participants in the Open-Label Extension Period.

Other Name: Copaxone

Intervention Type: Drug

Intervention Name: Placebo

Description: Placebo comparator administered by subcutaneous injection three times each week for 12 months during the Double-Blind Period.

Arm Group Label: Placebo / GA 40 mg

Eligibility

Criteria:

Inclusion Criteria:

1. Subjects must have a confirmed and documented MS diagnosis as defined by the Revised McDonald criteria with a relapsing-remitting disease course.

2. Subjects must be ambulatory with an EDSS score of 0-5.5 in both screening and baseline visits.

3. Subjects must be in a relapse-free, stable neurological condition and free of corticosteroid treatment [intravenous (IV), intramuscular (IM) and/or per os (PO)] or ACTH 30 days prior to screening (month -1) and between screening and baseline (month 0) visits.

4. Subjects must have experienced one of the following:

At least one documented relapse in the 12 months prior to screening, or At least two documented relapses in the 24 months prior to screening, or One documented relapse between 12 and 24 months prior to screening with at least one documented T1-Gd enhancing lesion in an MRI performed within 12 months prior to screening.

5. Subjects must be between 18 and 55 years of age, inclusive.

6. Women of child-bearing potential must practice an acceptable method of birth control.

7. Subjects must be able to sign and date a written informed consent prior to entering the study.

8. Subjects must be willing and able to comply with the protocol requirements for the duration of the study

Exclusion Criteria:

1. Subjects with progressive forms of MS.

2. Use of experimental or investigational drugs, and/or participation in drug clinical studies within the 6 months prior to screening.

3. Use of immunosuppressive (including Mitoxantrone and Fingolimod) or cytotoxic agents within 6 months prior to the screening visit.

4. Use of natalizumab (Tysabri®) or any other monoclonal antibodies within 2 years prior to screening.

5. Use of cladribine within 2 years prior to screening.

6. Previous treatment with immunomodulators (including IFNβ 1a and 1b, and IV Immunoglobulin (IVIg) within 2 months prior to screening.

7. Previous use of GA or any other glatiramoid.

8. Chronic (more than 30 consecutive days) systemic (IV, PO or IM) corticosteroid treatment within 6 months prior to screening visit.

9. Previous total body irradiation or total lymphoid irradiation.

10. Previous stem-cell treatment, autologous bone marrow transplantation or allogenic bone marrow transplantation.

11. Pregnancy or breastfeeding.

12. Subjects with a clinically significant or unstable medical or surgical condition that would preclude safe and complete study participation, as determined by medical history, physical exams, ECG, abnormal laboratory tests and chest X-ray. 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. A known history of sensitivity to Gadolinium.

14. Inability to successfully undergo MRI scanning.

15. A known drug hypersensitivity to Mannitol.

Gender: All

Minimum Age: 18 Years

Maximum Age: 55 Years

Healthy Volunteers: No

Location
Facility:
Teva Investigational Site 1332 | Birmingham, Alabama, 35209, United States
Teva Investigational Site 1327 | Gilbert, Arizona, 85234, United States
Teva Investigational Site 1311 | Phoenix, Arizona, 85004, United States
Teva Investigational Site 1326 | Fullerton, California, 92835, United States
Teva Investigational Site 1335 | La Jolla, California, 92037, United States
Teva Investigational Site 1297 | Aurora, Colorado, 80045, United States
Teva Investigational Site 1344 | Boulder, Colorado, 80304, United States
Teva Investigational Site 1315 | Centennial, Colorado, 80112, United States
Teva Investigational Site 1350 | Fort Collins, Colorado, 80528, United States
Teva Investigational Site 1345 | Miami, Florida, 33136, United States
Teva Investigational Site 1336 | Naples, Florida, 34102, United States
Teva Investigational Site 1347 | Pompano Beach, Florida, 33060, United States
Teva Investigational Site 1319 | Ponte Vedra, Florida, 32082, United States
Teva Investigational Site 1298 | Sarasota, Florida, 34233, United States
Teva Investigational Site 1316 | Sarasota, Florida, 34239, United States
Teva Investigational Site 1340 | Tampa, Florida, 33606, United States
Teva Investigational Site 1317 | Vero Beach, Florida, 32960, United States
Teva Investigational Site 1303 | Northbrook, Illinois, 60062, United States
Teva Investigational Site 1334 | Lenexa, Kansas, 66214, United States
Teva Investigational Site 1302 | Lexington, Kentucky, 40513, United States
Teva Investigational Site 1322 | Shreveport, Louisiana, 71103, United States
Teva Investigational Site 1306 | Detroit, Michigan, 48201, United States
Teva Investigational Site 1329 | Akron, Ohio, 44320, United States
Teva Investigational Site 1349 | Columbus, Ohio, 43221, United States
Teva Investigational Site 1313 | Dayton, Ohio, 45417, United States
Teva Investigational Site 1318 | Uniontown, Ohio, 44685, United States
Teva Investigational Site 1341 | Oklahoma City, Oklahoma, 73104, United States
Teva Investigational Site 1310 | Nashville, Tennessee, 37205, United States
Teva Investigational Site 1321 | Lubbock, Texas, 79410, United States
Teva Investigational Site 1337 | Round Rock, Texas, 78681, United States
Teva Investigational Site 1301 | San Antonio, Texas, 78231, United States
Teva Investigational Site 1346 | San Antonio, Texas, 78258, United States
Teva Investigational Site 1343 | Salt Lake City, Utah, 84106, United States
Teva Investigational Site 1338 | Richmond, Virginia, 23298-0599, United States
Teva Investigational Site 1339 | Roanoke, Virginia, 24018, United States
Teva Investigational Site 1300 | Vienna, Virginia, 22182, United States
Teva Investigational Site 1323 | Kirkland, Washington, 98034, United States
Teva Investigational Site 5940 | Blagoevgrad, 2700, Bulgaria
Teva Investigational Site 5931 | Pleven, 5800, Bulgaria
Teva Investigational Site 5932 | Pleven, 5800, Bulgaria
Teva Investigational Site 5933 | Plovdiv, 4000, Bulgaria
Teva Investigational Site 5936 | Ruse, 7000, Bulgaria
Teva Investigational Site 5935 | Shumen, 9700, Bulgaria
Teva Investigational Site 5939 | Sofia, 1000, Bulgaria
Teva Investigational Site 5921 | Sofia, 1113, Bulgaria
Teva Investigational Site 5922 | Sofia, 1113, Bulgaria
Teva Investigational Site 5926 | Sofia, 1309, Bulgaria
Teva Investigational Site 5938 | Sofia, 1407, Bulgaria
Teva Investigational Site 5924 | Sofia, 1431, Bulgaria
Teva Investigational Site 5927 | Sofia, 15257, Bulgaria
Teva Investigational Site 5923 | Sofia, 1606, Bulgaria
Teva Investigational Site 5925 | Sofia, 1606, Bulgaria
Teva Investigational Site 5928 | Sofia, 1606, Bulgaria
Teva Investigational Site 5929 | Sofia, 1606, Bulgaria
Teva Investigational Site 5934 | Stara Zagora, 6000, Bulgaria
Teva Investigational Site 5930 | Varna, 9010, Bulgaria
Teva Investigational Site 5937 | Veliko Tarnovo, 5000, Bulgaria
Teva Investigational Site 6011 | Osijek, 31 000, Croatia
Teva Investigational Site 6009 | Zagreb, 10000, Croatia
Teva Investigational Site 6010 | Zagreb, 10000, Croatia
Teva Investigational Site 6012 | Zagreb, 10000, Croatia
Teva Investigational Site 6013 | Zagreb, 10000, Croatia
Teva Investigational Site 5433 | Olomouc, 779 00, Czechia
Teva Investigational Site 5434 | Ostrava - poruba, 708 52, Czechia
Teva Investigational Site 5432 | Praha 10, 100 31, Czechia
Teva Investigational Site 5435 | Teplice, 415 29, Czechia
Teva Investigational Site 5513 | Kohtla-Jarve, 31025, Estonia
Teva Investigational Site 5510 | Tallinn, EE-10617, Estonia
Teva Investigational Site 5512 | Tartu, EE-51014, Estonia
Teva Investigational Site 8110 | Tbilisi, 0112, Georgia
Teva Investigational Site 8111 | Tbilisi, 0179, Georgia
Teva Investigational Site 3268 | Bad Wildbad, 75323, Germany
Teva Investigational Site 3272 | Bayreuth, 95445, Germany
Teva Investigational Site 3262 | Berlin, 10117, Germany
Teva Investigational Site 3276 | Berlin, 12203, Germany
Teva Investigational Site 3271 | Bonn, 53117, Germany
Teva Investigational Site 3265 | Dresden, 01307, Germany
Teva Investigational Site 3267 | Duesseldorf, 40211, Germany
Teva Investigational Site 3263 | Erbach, 64711, Germany
Teva Investigational Site 3269 | Hamburg, 22179, Germany
Teva Investigational Site 3266 | Hannover, 30171, Germany
Teva Investigational Site 3270 | Herborn, 35745, Germany
Teva Investigational Site 3273 | Kaltenkirchen, 24568, Germany
Teva Investigational Site 3275 | Marburg, 35043, Germany
Teva Investigational Site 3261 | Munster, 48149, Germany
Teva Investigational Site 3264 | Ulm, 89081, Germany
Teva Investigational Site 5127 | Budapest, H-1115, Hungary
Teva Investigational Site 5129 | Debrecen, 4043, Hungary
Teva Investigational Site 5130 | Eger, H-3300, Hungary
Teva Investigational Site 5132 | Esztergom, H-2500, Hungary
Teva Investigational Site 5131 | Gyor, H-9023, Hungary
Teva Investigational Site 5128 | Kaposvar, H-7400, Hungary
Teva Investigational Site 5133 | Veszprem, H-8200, Hungary
Teva Investigational Site 8052 | Ramat Gan, 5262160, Israel
Teva Investigational Site 3089 | Bologna, 40139, Italy
Teva Investigational Site 3084 | Cefalu, 90015, Italy
Teva Investigational Site 3092 | Cosenza, 87100, Italy
Teva Investigational Site 3080 | Milano, 20148, Italy
Teva Investigational Site 3086 | Rome, 00144, Italy
Teva Investigational Site 5710 | Kaunas, 50009, Lithuania
Teva Investigational Site 5712 | Siauliai, 76231, Lithuania
Teva Investigational Site 5711 | Vilnius, LT-08661, Lithuania
Teva Investigational Site 5374 | Czestochowa, 42-200, Poland
Teva Investigational Site 5377 | Elblag, 82-300, Poland
Teva Investigational Site 5381 | Gdansk, 80-299, Poland
Teva Investigational Site 5380 | Gdansk, 80-803, Poland
Teva Investigational Site 5376 | Gorzow Wielkopolski, 66-400, Poland
Teva Investigational Site 5372 | Grodzisk Mazowiecki, 05-825, Poland
Teva Investigational Site 5375 | Katowice, 40-684, Poland
Teva Investigational Site 5368 | Katowice, 40-752, Poland
Teva Investigational Site 5379 | Kielce, 25-726, Poland
Teva Investigational Site 5382 | Konskie, 26-200, Poland
Teva Investigational Site 5369 | Koscierzyna, 83-400, Poland
Teva Investigational Site 5378 | Krakow, 31-826, Poland
Teva Investigational Site 5366 | Lodz, 90-153, Poland
Teva Investigational Site 5373 | Olsztyn, 10-560, Poland
Teva Investigational Site 5384 | Poznan, 60-355, Poland
Teva Investigational Site 5371 | Szczecin, 70-111, Poland
Teva Investigational Site 5367 | Warszawa, 02-097, Poland
Teva Investigational Site 5370 | Wroclaw, 50-556, Poland
Teva Investigational Site 5233 | Balotesti, 077015, Romania
Teva Investigational Site 5222 | Bucharest, 010825, Romania
Teva Investigational Site 5221 | Bucuresti, 022328, Romania
Teva Investigational Site 5220 | Bucuresti, 050098, Romania
Teva Investigational Site 5227 | Cluj-Napoca, 400006, Romania
Teva Investigational Site 5230 | Cluj-Napoca, 400437, Romania
Teva Investigational Site 5225 | Constanta, 900123, Romania
Teva Investigational Site 5226 | Constanta, 900591, Romania
Teva Investigational Site 5232 | Craiova, 200515, Romania
Teva Investigational Site 5231 | Iasi, 700661, Romania
Teva Investigational Site 5223 | Piatra-Neamt, 610136, Romania
Teva Investigational Site 5228 | Sibiu, 550245, Romania
Teva Investigational Site 5229 | Targu-Mures, 540136, Romania
Teva Investigational Site 5224 | Timisoara, 300736, Romania
Teva Investigational Site 5063 | Barnaul, 656024, Russian Federation
Teva Investigational Site 5059 | Ekaterinburg, 620102, Russian Federation
Teva Investigational Site 5068 | Irkutsk, 664079, Russian Federation
Teva Investigational Site 5067 | Krasnoyarsk, 660022, Russian Federation
Teva Investigational Site 5052 | Moscow, 127015, Russian Federation
Teva Investigational Site 5057 | Nizhny Novgorod, 603126, Russian Federation
Teva Investigational Site 5062 | Novosibirsk, 630087, Russian Federation
Teva Investigational Site 5060 | Perm, 614990, Russian Federation
Teva Investigational Site 5053 | Saint Petersburg, 197022, Russian Federation
Teva Investigational Site 5058 | Samara, 443095, Russian Federation
Teva Investigational Site 5064 | Smolensk, 214018, Russian Federation
Teva Investigational Site 5056 | St. Petersburg, 194044, Russian Federation
Teva Investigational Site 5055 | St. Petersburg, 194354, Russian Federation
Teva Investigational Site 5054 | St. Petersburg, 197376, Russian Federation
Teva Investigational Site 5066 | Tomsk, 634050, Russian Federation
Teva Investigational Site 5061 | Ufa, 450007, Russian Federation
Teva Investigational Site 5065 | Yaroslavl, 150030, Russian Federation
Teva Investigational Site 9020 | Johannesburg, 2157, South Africa
Teva Investigational Site 9019 | Johannesburg, 2193, South Africa
Teva Investigational Site 9022 | Pietermaritzburg, 3201, South Africa
Teva Investigational Site 9025 | Pretoria, 0002, South Africa
Teva Investigational Site 9018 | Pretoria, 0041, South Africa
Teva Investigational Site 9021 | Rosebank, 2196, South Africa
Teva Investigational Site 9024 | Umhlanga, 4320, South Africa
Teva Investigational Site 5835 | Chernihiv, 14029, Ukraine
Teva Investigational Site 5834 | Chernivtsi, 58018, Ukraine
Teva Investigational Site 5827 | Dnipropetrovsk, 49027, Ukraine
Teva Investigational Site 5828 | Donetsk, 83003, Ukraine
Teva Investigational Site 5829 | Ivano-Frankivsk, 76008, Ukraine
Teva Investigational Site 5830 | Kharkiv, 61018, Ukraine
Teva Investigational Site 5833 | Kyiv, 03110, Ukraine
Teva Investigational Site 5836 | Kyiv, 03115, Ukraine
Teva Investigational Site 5825 | Lviv, 79010, Ukraine
Teva Investigational Site 5839 | Odesa, 65014, Ukraine
Teva Investigational Site 5832 | Poltava, 36024, Ukraine
Teva Investigational Site 5838 | Simferopol, 295017, Ukraine
Teva Investigational Site 5837 | Uzhgorod, 88018, Ukraine
Teva Investigational Site 5826 | Vinnytsya, 21005, Ukraine
Teva Investigational Site 5831 | Zaporizhzhya, 69600, Ukraine
Teva Investigational Site 3439 | Nottingham, NG7 2UH, United Kingdom
Teva Investigational Site 3438 | Salford, M6 8HD, United Kingdom
Teva Investigational Site 3440 | Sheffield, S10 2JF, United Kingdom
Location Countries

Bulgaria

Croatia

Czechia

Estonia

Georgia

Germany

Hungary

Israel

Italy

Lithuania

Poland

Romania

Russian Federation

South Africa

Ukraine

United Kingdom

United States

Verification Date

October 2018

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: GA 40 mg / GA 40 mg

Type: Experimental

Description: Also referred to as the 'Early Start' treatment arm, participants were administered glatiramer acetate (GA) 40 mg/mL by subcutaneous injection three times a week for 12 months during the Double-Blind Period, and then continued that treatment as open-label therapy until the drug was commercially available or development stopped.

Label: Placebo / GA 40 mg

Type: Placebo Comparator

Description: Also referred to as the 'Delayed Start' treatment arm, participants were administered placebo subcutaneous injections three times a week for 12 months during the Double-Blind Period, and then switched to GA 40 mg/mL subcutaneous injections three times a week as open-label therapy until the drug was commercially available or development stopped.

Acronym GALA
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Source: ClinicalTrials.gov