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 (GALA)

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

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

Study Overview

• Status: Completed
• Conditions: Relapsing Remitting Multiple Sclerosis
• Intervention / Treatment: Drug: Glatiramer acetate (GA); Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 1404
• Phase: Phase 3

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GA 40 mg / GA 40 mg; 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.	Drug: Glatiramer acetate (GA); 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 Names: Copaxone
Placebo Comparator: Placebo / GA 40 mg; 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.	Drug: Glatiramer acetate (GA); 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 Names: Copaxone; Drug: Placebo; Placebo comparator administered by subcutaneous injection three times each week for 12 months during the Double-Blind Period.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Number of Confirmed Relapses During the Placebo Controlled (PC) Treatment Period Estimated by Negative Binomial Regression	Relapses were monitored throughout the study. During the PC Period, two neurologists/physicians assessed subjects' general medical and neurological evaluations separately. A relapse was defined as the appearance of 1+ new neurological abnormalities or the reappearance of 1+ previously observed neurological abnormalities lasting >= 48 hours and immediately preceded by an improving neurological state of at >=30 days from onset of previous relapse. An event was counted as a relapse only when the subject's symptoms were accompanied by observed objective neurological changes, consistent with >= one of the following: - An increase of >= 0.5 in the Expanded Disability Status Scale (EDSS) score as compared to previous evaluation. - An increase of one grade in the actual score of >=2 of the 7 functional systems (FS), as compared to previous evaluation. - An increase of 2 grades in the actual score of one FS as compared to the previous evaluation. Adjusted mean values are displayed.	Day 1 to 12 months
Annualized Rate of Confirmed Relapses Comparing Early Starters to Delayed Starters Estimated by Negative Binomial Regression	The annualized relapse rate (ARR) was calculated for the study by dividing the cumulative number of confirmed relapses by the number of person-years of exposure to treatment. The analysis of the annualized relapse rate is based on estimating a contrast (early start vs delayed start) derived from a baseline-adjusted, Negative Binomial Regression model to the number of confirmed relapses observed during study (post randomization) with an "offset" based on the log of exposure to treatment.	Day 1 up to 6.5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	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	T2 lesions are hyperintense brain lesions that show on magnetic resonance imaging (MRI) and are associated with multiple sclerosis. The cumulative number of T2 lesions at Months 6 and 12 that are new or enlarged as compared to the baseline MRI are offered. Note that the two timeframes (Months 6 and 12) are combined. Adjusted mean is based on negative binomial regression, adjusted for baseline number of T2 lesions and country or geographical region as covariates.	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	The cumulative number of gadolinium (Gd)-enhanced lesions on T1-weighted images at Months 6 and 12 as compared to the baseline MRI are offered. Note that the two timeframes (Months 6 and 12) are combined. Adjusted mean is based on negative binomial regression with an "offset" employing the log of the proportion of the number of the available post-baseline scans to adjust for missing MRI scans (if any), adjusted for baseline number of enhancing lesions on T1-weighted images and country or geographical region as covariates.	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	The analysis of brain atrophy as defined by the percentage change in normalized brain volume from baseline to Month 12 was based on the outcome of a contrast (GA 40 mg TIW vs. placebo) derived from a baseline-adjusted ANCOVA. In addition to the treatment group, the model included the following covariates: - SIENAX normalized brain volume at baseline. - The number of enhancing lesions on T1-weighted images at baseline. - country or geographical region. Sienax estimates total brain tissue volume, from a single image, normalised for skull size.	Baseline (Day -7), Month 12
The Number of New/Enlarging T2 Lesions at Months 6, 12 and 36 Estimated by Negative Binomial Regression	All data accumulated from screening, the PC Treatment period up to the end of the Open Label (OL) period are combined and referred to as the Long Term Period. T2 lesions are hyperintense brain lesions that show on magnetic resonance imaging (MRI) and are associated with multiple sclerosis. The number of T2 lesions at Months 6, 12 and 36 that are new or enlarged as compared to the baseline MRI are offered. Adjusted mean is based on negative binomial regression, adjusted for baseline number of T2 lesions and country or geographical region as covariates. An "offset" employing the log of the proportion of the number of the available post-placebo-controlled baseline (PCBL) scans was used to adjust for missing MRI scans.	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	All data accumulated from screening, the PC Treatment period up to the end of the Open Label (OL) period are combined and referred to as the Long Term Period. The cumulative number of gadolinium (Gd)-enhanced lesions on T1-weighted images at Months 6, 12 and 36 as compared to the baseline MRI are offered. Adjusted mean is based on negative binomial regression The model was fit using an autoregressive covariance structure. Covariates used: number of enhancing lesions on T1-weighted images at placebo-controlled baseline and country or geographical region. The cumulative number is derived from all the data points before it. For example, if the participant skipped one time point in between the baseline and 36 months, then it cannot be calculated.	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	The analysis of brain atrophy as defined by the percentage change in brain volume from baseline to Months 6, 12 and 36 was performed using mixed model for repeated measures (MMRM) with SIENAX normalized brain volume at baseline, number of Gd-enhancing lesions at baseline, and country or geographical region as fixed effects. Sienax estimates total brain tissue volume, from a single image, normalised for skull size.	Baseline (Day -7), Month 6, Month 12, Month 36
Participants With Treatment-Emergent Adverse Events (TEAEs)	Adverse events (AEs) summarized in this table are those that began or worsened after treatment with study drug (treatment-emergent AEs). An adverse event was defined in the protocol as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Severity was rated by the investigator on a scale of mild, moderate and severe, with severe= an AE which prevents normal daily activities. Relation of AE to treatment was determined by the investigator. Serious AEs include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, OR an important medical event that jeopardized the patient and required medical intervention to prevent the previously listed serious outcomes.	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

Collaborators and Investigators

• Sponsor: Teva Branded Pharmaceutical Products R&D, Inc.

Publications and helpful links

General Publications

• Khan O, Rieckmann P, Boyko A, Selmaj K, Ashtamker N, Davis MD, Kolodny S, Zivadinov R. Efficacy and safety of a three-times-weekly dosing regimen of glatiramer acetate in relapsing-remitting multiple sclerosis patients: 3-year results of the Glatiramer Acetate Low-Frequency Administration open-label extension study. Mult Scler. 2017 May;23(6):818-829. doi: 10.1177/1352458516664033. Epub 2016 Aug 8.

Study record dates

Study Major Dates

• Study Start (Actual): June 22, 2010
• Primary Completion (Actual): May 8, 2012
• Study Completion (Actual): May 12, 2017

Study Registration Dates

• First Submitted: February 10, 2010
• First Submitted That Met QC Criteria: February 10, 2010
• First Posted (Estimate): February 11, 2010

Study Record Updates

• Last Update Posted (Actual): December 9, 2021
• Last Update Submitted That Met QC Criteria: December 7, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: Relapsing Remitting Multiple Sclerosis; Glatiramer Acetate
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Physiological Effects of Drugs; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Adjuvants, Immunologic; Glatiramer Acetate; (T,G)-A-L
• Other Study ID Numbers: MS-GA-301; 2009-018084-27 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No