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

NCT01067521 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: MS-GA-3012009-018084-27
• Study Type: interventional
• Target: 1,404
• Locations: 17 countries
• Sites: 176

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

Conditions

Relapsing Remitting Multiple Sclerosis

Keywords

Relapsing Remitting Multiple Sclerosis; Glatiramer Acetate

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (7)

• 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

Study Arms (2)

GA 40 mg / GA 40 mg

EXPERIMENTAL

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)

Placebo / GA 40 mg

PLACEBO COMPARATOR

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); Drug: Placebo

Interventions

Glatiramer acetate (GA) DRUG

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.

Also known as: Copaxone

GA 40 mg / GA 40 mg; Placebo / GA 40 mg

Placebo DRUG

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

Placebo / GA 40 mg

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects must have a confirmed and documented MS diagnosis as defined by the Revised McDonald criteria with a relapsing-remitting disease course.
• Subjects must be ambulatory with an EDSS score of 0-5.5 in both screening and baseline visits.
• 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.
• 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.
• Subjects must be between 18 and 55 years of age, inclusive.
• Women of child-bearing potential must practice an acceptable method of birth control.
• Subjects must be able to sign and date a written informed consent prior to entering the study.
• Subjects must be willing and able to comply with the protocol requirements for the duration of the study

You may not qualify if:

• Subjects with progressive forms of MS.
• Use of experimental or investigational drugs, and/or participation in drug clinical studies within the 6 months prior to screening.
• Use of immunosuppressive (including Mitoxantrone and Fingolimod) or cytotoxic agents within 6 months prior to the screening visit.
• Use of natalizumab (Tysabri®) or any other monoclonal antibodies within 2 years prior to screening.
• Use of cladribine within 2 years prior to screening.
• Previous treatment with immunomodulators (including IFNβ 1a and 1b, and IV Immunoglobulin (IVIg) within 2 months prior to screening.
• Previous use of GA or any other glatiramoid.
• Chronic (more than 30 consecutive days) systemic (IV, PO or IM) corticosteroid treatment within 6 months prior to screening visit.
• Previous total body irradiation or total lymphoid irradiation.
• Previous stem-cell treatment, autologous bone marrow transplantation or allogenic bone marrow transplantation.
• Pregnancy or breastfeeding.
• 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.
• A known history of sensitivity to Gadolinium.
• Inability to successfully undergo MRI scanning.
• A known drug hypersensitivity to Mannitol.

Sponsors & Collaborators

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

Study Sites (176)

Teva Investigational Site 1332

Birmingham, Alabama, 35209, United States

Location

Teva Investigational Site 1327

Gilbert, Arizona, 85234, United States

Location

Teva Investigational Site 1311

Phoenix, Arizona, 85004, United States

Location

Teva Investigational Site 1326

Fullerton, California, 92835, United States

Location

Teva Investigational Site 1335

La Jolla, California, 92037, United States

Location

Teva Investigational Site 1297

Aurora, Colorado, 80045, United States

Location

Teva Investigational Site 1344

Boulder, Colorado, 80304, United States

Location

Teva Investigational Site 1315

Centennial, Colorado, 80112, United States

Location

Teva Investigational Site 1350

Fort Collins, Colorado, 80528, United States

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Teva Investigational Site 1345

Miami, Florida, 33136, United States

Location

Teva Investigational Site 1336

Naples, Florida, 34102, United States

Location

Teva Investigational Site 1347

Pompano Beach, Florida, 33060, United States

Location

Teva Investigational Site 1319

Ponte Vedra, Florida, 32082, United States

Location

Teva Investigational Site 1298

Sarasota, Florida, 34233, United States

Location

Teva Investigational Site 1316

Sarasota, Florida, 34239, United States

Location

Teva Investigational Site 1340

Tampa, Florida, 33606, United States

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Teva Investigational Site 1317

Vero Beach, Florida, 32960, United States

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Teva Investigational Site 1303

Northbrook, Illinois, 60062, United States

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Teva Investigational Site 1334

Lenexa, Kansas, 66214, United States

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Teva Investigational Site 1302

Lexington, Kentucky, 40513, United States

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Teva Investigational Site 1322

Shreveport, Louisiana, 71103, United States

Location

Teva Investigational Site 1306

Detroit, Michigan, 48201, United States

Location

Teva Investigational Site 1329

Akron, Ohio, 44320, United States

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Teva Investigational Site 1349

Columbus, Ohio, 43221, United States

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Teva Investigational Site 1313

Dayton, Ohio, 45417, United States

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Teva Investigational Site 1318

Uniontown, Ohio, 44685, United States

Location

Teva Investigational Site 1341

Oklahoma City, Oklahoma, 73104, United States

Location

Teva Investigational Site 1310

Nashville, Tennessee, 37205, United States

Location

Teva Investigational Site 1321

Lubbock, Texas, 79410, United States

Location

Teva Investigational Site 1337

Round Rock, Texas, 78681, United States

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Teva Investigational Site 1301

San Antonio, Texas, 78231, United States

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Teva Investigational Site 1346

San Antonio, Texas, 78258, United States

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Teva Investigational Site 1343

Salt Lake City, Utah, 84106, United States

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Teva Investigational Site 1338

Richmond, Virginia, 23298-0599, United States

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Teva Investigational Site 1339

Roanoke, Virginia, 24018, United States

Location

Teva Investigational Site 1300

Vienna, Virginia, 22182, United States

Location

Teva Investigational Site 1323

Kirkland, Washington, 98034, United States

Location

Teva Investigational Site 5940

Blagoevgrad, 2700, Bulgaria

Location

Teva Investigational Site 5931

Pleven, 5800, Bulgaria

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Teva Investigational Site 5932

Pleven, 5800, Bulgaria

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Teva Investigational Site 5933

Plovdiv, 4000, Bulgaria

Location

Teva Investigational Site 5936

Rousse, 7000, Bulgaria

Location

Teva Investigational Site 5935

Shumen, 9700, Bulgaria

Location

Teva Investigational Site 5939

Sofia, 1000, Bulgaria

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Teva Investigational Site 5921

Sofia, 1113, Bulgaria

Location

Teva Investigational Site 5922

Sofia, 1113, Bulgaria

Location

Teva Investigational Site 5926

Sofia, 1309, Bulgaria

Location

Teva Investigational Site 5938

Sofia, 1407, Bulgaria

Location

Teva Investigational Site 5924

Sofia, 1431, Bulgaria

Location

Teva Investigational Site 5927

Sofia, 15257, Bulgaria

Location

Teva Investigational Site 5923

Sofia, 1606, Bulgaria

Location

Teva Investigational Site 5925

Sofia, 1606, Bulgaria

Location

Teva Investigational Site 5928

Sofia, 1606, Bulgaria

Location

Teva Investigational Site 5929

Sofia, 1606, Bulgaria

Location

Teva Investigational Site 5934

Stara Zagora, 6000, Bulgaria

Location

Teva Investigational Site 5930

Varna, 9010, Bulgaria

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Teva Investigational Site 5937

Veliko Tarnovo, 5000, Bulgaria

Location

Teva Investigational Site 6011

Osijek, 31 000, Croatia

Location

Teva Investigational Site 6009

Zagreb, 10000, Croatia

Location

Teva Investigational Site 6010

Zagreb, 10000, Croatia

Location

Teva Investigational Site 6012

Zagreb, 10000, Croatia

Location

Teva Investigational Site 6013

Zagreb, 10000, Croatia

Location

Teva Investigational Site 5433

Olomouc, 779 00, Czechia

Location

Teva Investigational Site 5434

Ostrava - Poruba, 708 52, Czechia

Location

Teva Investigational Site 5432

Prague, 100 31, Czechia

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Teva Investigational Site 5435

Teplice, 415 29, Czechia

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Teva Investigational Site 5513

Kohtla-Järve, 31025, Estonia

Location

Teva Investigational Site 5510

Tallinn, EE-10617, Estonia

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Teva Investigational Site 5512

Tartu, EE-51014, Estonia

Location

Teva Investigational Site 8110

Tbilisi, 0112, Georgia

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Teva Investigational Site 8111

Tbilisi, 0179, Georgia

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Teva Investigational Site 3268

Bad Wildbad, 75323, Germany

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Teva Investigational Site 3272

Bayreuth, 95445, Germany

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Teva Investigational Site 3262

Berlin, 10117, Germany

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Teva Investigational Site 3276

Berlin, 12203, Germany

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Teva Investigational Site 3271

Bonn, 53117, Germany

Location

Teva Investigational Site 3265

Dresden, 01307, Germany

Location

Teva Investigational Site 3267

Düsseldorf, 40211, Germany

Location

Teva Investigational Site 3263

Erbach im Odenwald, 64711, Germany

Location

Teva Investigational Site 3269

Hamburg, 22179, Germany

Location

Teva Investigational Site 3266

Hanover, 30171, Germany

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Teva Investigational Site 3270

Herborn, 35745, Germany

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Teva Investigational Site 3273

Kaltenkirchen, 24568, Germany

Location

Teva Investigational Site 3275

Marburg, 35043, Germany

Location

Teva Investigational Site 3261

Münster, 48149, Germany

Location

Teva Investigational Site 3264

Ulm, 89081, Germany

Location

Teva Investigational Site 5127

Budapest, H-1115, Hungary

Location

Teva Investigational Site 5129

Debrecen, 4043, Hungary

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Teva Investigational Site 5130

Eger, H-3300, Hungary

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Teva Investigational Site 5132

Esztergom, H-2500, Hungary

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Teva Investigational Site 5131

Győr, H-9023, Hungary

Location

Teva Investigational Site 5128

Kaposvár, H-7400, Hungary

Location

Teva Investigational Site 5133

Veszprém, H-8200, Hungary

Location

Teva Investigational Site 8052

Ramat Gan, 5262160, Israel

Location

Teva Investigational Site 3089

Bologna, 40139, Italy

Location

Teva Investigational Site 3084

Cefalù, 90015, Italy

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Teva Investigational Site 3092

Cosenza, 87100, Italy

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Teva Investigational Site 3080

Milan, 20148, Italy

Location

Teva Investigational Site 3086

Rome, 00144, Italy

Location

Teva Investigational Site 5710

Kaunas, 50009, Lithuania

Location

Teva Investigational Site 5712

Šiauliai, 76231, Lithuania

Location

Teva Investigational Site 5711

Vilnius, LT-08661, Lithuania

Location

Teva Investigational Site 5374

Częstochowa, 42-200, Poland

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Teva Investigational Site 5377

Elblag, 82-300, Poland

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Teva Investigational Site 5381

Gdansk, 80-299, Poland

Location

Teva Investigational Site 5380

Gdansk, 80-803, Poland

Location

Teva Investigational Site 5382

Gmina Końskie, 26-200, Poland

Location

Teva Investigational Site 5376

Gorzów Wielkopolski, 66-400, Poland

Location

Teva Investigational Site 5372

Grodzisk Mazowiecki, 05-825, Poland

Location

Teva Investigational Site 5375

Katowice, 40-684, Poland

Location

Teva Investigational Site 5368

Katowice, 40-752, Poland

Location

Teva Investigational Site 5379

Kielce, 25-726, Poland

Location

Teva Investigational Site 5369

Kościerzyna, 83-400, Poland

Location

Teva Investigational Site 5378

Krakow, 31-826, Poland

Location

Teva Investigational Site 5366

Lodz, 90-153, Poland

Location

Teva Investigational Site 5373

Olsztyn, 10-560, Poland

Location

Teva Investigational Site 5384

Poznan, 60-355, Poland

Location

Teva Investigational Site 5371

Szczecin, 70-111, Poland

Location

Teva Investigational Site 5367

Warsaw, 02-097, Poland

Location

Teva Investigational Site 5370

Wroclaw, 50-556, Poland

Location

Teva Investigational Site 5233

Baloteşti, 077015, Romania

Location

Teva Investigational Site 5222

Bucharest, 010825, Romania

Location

Teva Investigational Site 5221

Bucharest, 022328, Romania

Location

Teva Investigational Site 5220

Bucharest, 050098, Romania

Location

Teva Investigational Site 5227

Cluj-Napoca, 400006, Romania

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Teva Investigational Site 5230

Cluj-Napoca, 400437, Romania

Location

Teva Investigational Site 5225

Constanța, 900123, Romania

Location

Teva Investigational Site 5226

Constanța, 900591, Romania

Location

Teva Investigational Site 5232

Craiova, 200515, Romania

Location

Teva Investigational Site 5231

Iași, 700661, Romania

Location

Teva Investigational Site 5223

Piatra Neamţ, 610136, Romania

Location

Teva Investigational Site 5228

Sibiu, 550245, Romania

Location

Teva Investigational Site 5229

Târgu Mureş, 540136, Romania

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Teva Investigational Site 5224

Timișoara, 300736, Romania

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Teva Investigational Site 5063

Barnaul, 656024, Russia

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Teva Investigational Site 5068

Irkutsk, 664079, Russia

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Teva Investigational Site 5067

Krasnoyarsk, 660022, Russia

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Teva Investigational Site 5052

Moscow, 127015, Russia

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Teva Investigational Site 5057

Nizhny Novgorod, 603126, Russia

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Teva Investigational Site 5062

Novosibirsk, 630087, Russia

Location

Teva Investigational Site 5060

Perm, 614990, Russia

Location

Teva Investigational Site 5056

Saint Petersburg, 194044, Russia

Location

Teva Investigational Site 5055

Saint Petersburg, 194354, Russia

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Teva Investigational Site 5053

Saint Petersburg, 197022, Russia

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Teva Investigational Site 5054

Saint Petersburg, 197376, Russia

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Teva Investigational Site 5058

Samara, 443095, Russia

Location

Teva Investigational Site 5064

Smolensk, 214018, Russia

Location

Teva Investigational Site 5066

Tomsk, 634050, Russia

Location

Teva Investigational Site 5061

Ufa, 450007, Russia

Location

Teva Investigational Site 5065

Yaroslavl, 150030, Russia

Location

Teva Investigational Site 5059

Yekaterinburg, 620102, Russia

Location

Teva Investigational Site 9020

Johannesburg, 2157, South Africa

Location

Teva Investigational Site 9019

Johannesburg, 2193, South Africa

Location

Teva Investigational Site 9022

Pietermaritzburg, 3201, South Africa

Location

Teva Investigational Site 9025

Pretoria, 0002, South Africa

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Teva Investigational Site 9018

Pretoria, 0041, South Africa

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Teva Investigational Site 9021

Rosebank, 2196, South Africa

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Teva Investigational Site 9024

Umhlanga, 4320, South Africa

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Teva Investigational Site 5835

Chernihiv, 14029, Ukraine

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Teva Investigational Site 5834

Chernivtsi, 58018, Ukraine

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Teva Investigational Site 5827

Dnipropetrovsk, 49027, Ukraine

Location

Teva Investigational Site 5828

Donetsk, 83003, Ukraine

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Teva Investigational Site 5829

Ivano-Frankivsk, 76008, Ukraine

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Teva Investigational Site 5830

Kharkiv, 61018, Ukraine

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Teva Investigational Site 5833

Kyiv, 03110, Ukraine

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Teva Investigational Site 5836

Kyiv, 03115, Ukraine

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Teva Investigational Site 5825

Lviv, 79010, Ukraine

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Teva Investigational Site 5839

Odesa, 65014, Ukraine

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Teva Investigational Site 5832

Poltava, 36024, Ukraine

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Teva Investigational Site 5838

Simferopol, 295017, Ukraine

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Teva Investigational Site 5837

Uzhhorod, 88018, Ukraine

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Teva Investigational Site 5826

Vinnytsia, 21005, Ukraine

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Teva Investigational Site 5831

Zaporizhzhya, 69600, Ukraine

Location

Teva Investigational Site 3439

Nottingham, NG7 2UH, United Kingdom

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Teva Investigational Site 3438

Salford, M6 8HD, United Kingdom

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Teva Investigational Site 3440

Sheffield, S10 2JF, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 27503905 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting

Interventions

Glatiramer Acetate

Condition Hierarchy (Ancestors)

Multiple Sclerosis; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Peptides; Amino Acids, Peptides, and Proteins

Limitations and Caveats

Analyses of Open-Label Period data are not adjusted for multiplicity and therefore do not control for type one statistical error.

Results Point of Contact

• Title: Director, Clinical Research
• Organization: Teva Branded Pharmaceutical Products, R&D Inc

info.era-clinical@teva.de

001-215-591-3000

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 10, 2010
• First Posted: February 11, 2010
• Study Start: June 22, 2010
• Primary Completion: May 8, 2012
• Study Completion: May 12, 2017
• Last Updated: December 9, 2021
• Results First Posted: October 9, 2018

Record last verified: 2021-12

Locations

CZ (4); RU (17); CR (5); ES (3); GE (2); IT (5); ZA (7); BU (20); HU (7); LI (3); RO (14); UA (15); DE (15); IL (1); US (37); GB (3); PL (18)