Efficacy and Safety of GTR in Comparison to Copaxone®

NCT ID: NCT01489254

Last Updated: 2016-12-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 794 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-10-31
• Study Completion Date: 2015-01-31

Brief Summary

The purpose of this study is demonstrate that efficacy and safety of Synthon's glatiramer acetate (GTR) is equivalent to Copaxone® (Teva) in patients with relapsing remitting multiple sclerosis

Detailed Description

GTR is being developed by Synthon as a similar version of Copaxone®. GTR has a similar quantitative and qualitative composition as Copaxone®, with regard to active substance and excipients and is presented in the same dosage form (pre-filled syringe containing a solution for injection). Introduction of GTR is anticipated to have a price lowering effect and will give doctors and patients more choice in the pharmaceutical armamentarium for MS.

This trial consists of two parts:

Part 1 is a multi-country, multi-centre, randomized, double-blind, active and placebo-controlled, equivalence trial comparing the efficacy and safety and tolerability of GTR versus Copaxone® in subjects with RRMS. Eligible subjects will be randomly assigned to receive daily 20 mg GTR (Synthon BV), 20 mg Copaxone® (TEVA) or placebo for a period of 9 months.

In Part 2, the trial continues as an open-label uncontrolled trial to evaluate efficacy and safety of long-term treatment with GTR. Subjects completing the 9-month double-blind period will be treated with open-label 20 mg daily GTR for another 15 months.

Conditions

Multiple Sclerosis

Keywords

Multiple Sclerosis,; Relapsing-Remitting Multiple Sclerosis,; glatiramer acetate,; MRI,; lesions,; MS relapse rate,; Copaxone

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

GTR

Drug

Group Type: EXPERIMENTAL

Glatiramer Acetate (GTR)

Intervention Type: DRUG

Glatiramer Acetate (GTR) 20 mg daily, for 9 months (Part 1) followed by additional 15 month treatment period (Part 2)

Copaxone®

Drug

Group Type: ACTIVE_COMPARATOR

Glatiramer Acetate (Copaxone®)

Intervention Type: DRUG

Glatiramer Acetate (Copaxone), 20 mg daily, for 9 months followed by additional 15 month GTR 20 mg daily treatment period (Part 2)

Placebo

Drug

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo (daily) for 9 months followed by additional 15 month GTR 20 mg daily treatment period (Part 2)

Interventions

Glatiramer Acetate (GTR)

Glatiramer Acetate (GTR) 20 mg daily, for 9 months (Part 1) followed by additional 15 month treatment period (Part 2)

Intervention Type: DRUG

Glatiramer Acetate (Copaxone®)

Glatiramer Acetate (Copaxone), 20 mg daily, for 9 months followed by additional 15 month GTR 20 mg daily treatment period (Part 2)

Intervention Type: DRUG

Placebo

Placebo (daily) for 9 months followed by additional 15 month GTR 20 mg daily treatment period (Part 2)

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Willing and able to sign written Informed Consent;
• Female and male subjects aged 18-55 years inclusive at the time of Informed Consent signing;
• Diagnosis of RRMS according to the revised McDonald criteria;
• Expanded Disability Status Scale (EDSS) score of 0.0 up to and including 5.5;
• Neurologically stable with no evidence of relapse within 30 days prior to randomization;
• Experienced at least 1 relapse in the year before first screening assessment;
• At least 1 T1-weighted Gadolinium enhancing (T1-GdE) lesion on routine brain MRI taken within 3 months of starting screening or on screening brain MRI (as confirmed by central imaging laboratory;
• Having a routine brain MRI showing maximally 15 T1-GdE lesions if scan is taken without subject receiving immuno-modulatory treatment, or a routine brain MRI showing maximally 5 T1-GdE lesions when taken while on immuno-modulatory treatment, or a screening MRI showing maximally 15 T1-GdE lesions;
• Must decline initiation or continuation of treatment with other available disease-modifying drugs for MS, for whatever reason, after having been informed about their respective benefits and possible adverse events by the investigator;
• Female subjects of childbearing potential must agree to practice appropriate contraceptive methods as assessed by the investigator.

Exclusion Criteria

• Any life-threatening, medically unstable or otherwise clinically significant condition or findings other than MS, in particular neoplastic disease, seizure disorders, or psychiatric disease;
• Any clinically significant deviation from reference ranges in laboratory tests;
• Positive laboratory test results for human immunodeficiency virus (HIV), HBsAg or HCV at screening;
• Any significant deviation from reference ranges for hepatic function;
• Positive urine drug screen or history of substance abuse within the year before screening (any use of illicit or prescription drugs or alcohol constituting an abuse pattern in the opinion of the investigator);
• Having been treated with or having received

1. at any time:

• glatiramer acetate, cladribine, rituximab, cyclophosphamide, alemtuzumab, or other immunosuppressive treatments with effects potentially lasting for more than 6 months
• total lymphoid irradiation or bone marrow transplantation

2. within one year before screening:

• mitoxantrone, but subject cannot be enrolled when mitoxantrone was taken at a cumulative lifetime dosing above 100 mg/m2

3. within 6 months before screening:

• fingolimod, immunoglobulins and/or monoclonal antibodies (including natalizumab), leflunomide, or putative MS treatments
• chronic oral or injected corticosteroids or injected ACTH (more than 30 consecutive days)

4. within 3 months before screening:

• azathioprine, methotrexate
• plasma exchange
• any other experimental intervention, in particular experimental drugs

5. within 1 month before screening:

• Interferon-β 1a or 1b
• short-term oral or injectable corticosteroids for treatment of a relapse
• short-term ACTH
• Having, in the opinion of the investigator, consecutively failed on efficacy grounds two full and adequate courses of accepted treatment modalities (normally at least one year of treatment for each);
• Pregnancy or breastfeeding;
• Known hypersensitivity to gadolinium-containing products, glatiramer acetate or mannitol;
• Having an estimated glomerular filtration rate (eGFR) < 50 mL/min/1.73m2;
• Inability to undergo (repeat) MRI investigations as judged by the investigator, e.g. due to claustrophobia, metal implants or fragments, tattoos or permanent make-up;
• Any reason why, in the investigator's opinion, the subject should not participate.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Synthon BV

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Synthon investigational site 112

Irvine, California, United States

Synthon investigational site 120

Port Charlotte, Florida, United States

Synthon investigational site 130

Sunrise, Florida, United States

Synthon investigational site 107

Elk Grove Village, Illinois, United States

Synthon investigational site 141

Raleigh, North Carolina, United States

Synthon investigational site 106

Cleveland, Ohio, United States

Synthon investigational site 135

Dayton, Ohio, United States

Synthon investigational site 401

Bitebsk, , Belarus

Synthon investigational site 403

Grodno, , Belarus

Synthon investigational site 402

Homyel, , Belarus

Synthon investigational site 404

Minsk, , Belarus

Synthon investigational site 407

Minsk, , Belarus

Synthon investigational site 408

Minsk, , Belarus

Synthon investigational site 405

Vitebsk, , Belarus

Synthon investigational site 486

Banja Luka, , Bosnia and Herzegovina

Synthon investigational site 487

Sarajevo, , Bosnia and Herzegovina

Synthon investigational site 488

Tuzla, , Bosnia and Herzegovina

Synthon investigational site 204

Pleven, , Bulgaria

Synthon investigational site 207

Pleven, , Bulgaria

Synthon investigational site 206

Plovdiv, , Bulgaria

Synthon investigational site 202

Sofia, , Bulgaria

Synthon investigational site 203

Sofia, , Bulgaria

Synthon investigational site 205

Sofia, , Bulgaria

Synthon investigational site 208

Sofia, , Bulgaria

Synthon investigational site 201

Varna, , Bulgaria

Synthon investigational site 477

Osijek, , Croatia

Synthon investigational site 475

Zagreb, , Croatia

Synthon investigational site 476

Zagreb, , Croatia

Synthon investigational site 478

Zagreb, , Croatia

Synthon investigational site 211

Brno, , Czechia

Synthon investigational site 217

Brno, , Czechia

Synthon investigational site 210

Olomouc, , Czechia

Synthon investigational site 212

Ostrava, , Czechia

Synthon investigational site 215

Prague, , Czechia

Synthon investigational site 216

Prague, , Czechia

Synthon investigational site 214

Teplice, , Czechia

Synthon investigational site 297

Kohtla-Järve, , Estonia

Synthon investigational site 296

Tallinn, , Estonia

Synthon investigational site 526

Tbilisi, , Georgia

Synthon investigational site 527

Tbilisi, , Georgia

Synthon investigational site 528

Tbilisi, , Georgia

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Tbilisi, , Georgia

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Tbilisi, , Georgia

Synthon investigational site 227

Jena, , Germany

Synthon investigational site 234

Coppito, , Italy

Synthon investigational site 235

Naples, , Italy

Synthon investigational site 516

Guadalajara, , Mexico

Synthon investigational site 512

Mexico City, , Mexico

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Mexico City, , Mexico

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Morelia, , Mexico

Synthon investigational site 547

Chisinau, , Moldova

Synthon investigational site 548

Chisinau, , Moldova

Synthon investigational site 549

Chisinau, , Moldova

Synthon investigational site 550

Chisinau, , Moldova

Synthon investigational site 244

Bialystok, , Poland

Synthon investigational site 240

Katowice, , Poland

Synthon investigational site 241

Katowice, , Poland

Synthon investigational site 242

Katowice, , Poland

Synthon investigational site 245

Katowice, , Poland

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Lodz, , Poland

Synthon investigational site 251

Lublin, , Poland

Synthon investigational site 243

Olsztyn, , Poland

Synthon investigational site 248

Poznan, , Poland

Synthon investigational site 250

Szczecin, , Poland

Synthon investigational site 246

Warsaw, , Poland

Synthon investigational site 249

Wroclaw, , Poland

Synthon investigational site 260

Bucharest, , Romania

Synthon investigational site 262

Bucharest, , Romania

Synthon investigational site 263

Bucharest, , Romania

Synthon investigational site 264

Bucharest, , Romania

Synthon investigational site 265

Bucharest, , Romania

Synthon investigational site 266

Cluj-Napoca, , Romania

Synthon investigational site 267

Timișoara, , Romania

Synthon investigational site 438

Arkhangelsk, , Russia

Synthon investigational site 435

Barnaul, , Russia

Synthon investigational site 437

Belgorod, , Russia

Synthon investigational site 445

Kaluga, , Russia

Synthon investigational site 427

Kazan', , Russia

Synthon investigational site 432

Kemerovo, , Russia

Synthon investigational site 447

Kirov, , Russia

Synthon investigational site 446

Lipetsk, , Russia

Synthon investigational site 571

Moscow, , Russia

Synthon investigational site 428

Nizhny Novgorod, , Russia

Synthon investigational site 429

Nizhny Novgorod, , Russia

Synthon investigational site 434

Novosibirsk, , Russia

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Novosibirsk, , Russia

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Penza, , Russia

Synthon investigational site 433

Pyatigorsk, , Russia

Synthon investigational site 421

Saint Petersburg, , Russia

Synthon investigational site 426

Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

Synthon investigational site 424

Samara, , Russia

Synthon investigational site 420

Smolensk, , Russia

Synthon investigational site 422

Tomsk, , Russia

Synthon investigational site 441

Tver', , Russia

Synthon investigational site 425

Tyumen, , Russia

Synthon investigational site 423

Ufa, , Russia

Synthon investigational site 431

Yekaterinburg, , Russia

Synthon investigational site 450

Belgrade, , Serbia

Synthon investigational site 451

Belgrade, , Serbia

Synthon investigational site 453

Kragujevac, , Serbia

Synthon investigational site 452

Novi Sad, , Serbia

Synthon investigational site 501

Cape Town, , South Africa

Synthon investigational site 505

Durban, , South Africa

Synthon investigational site 502

Pretoria, , South Africa

Synthon investigational site 474

Cherkassy, , Ukraine

Synthon investigational site 459

Chernihiv, , Ukraine

Synthon investigational site 463

Chernivtsi, , Ukraine

Synthon investigational site 458

Dnipro, , Ukraine

Synthon investigational site 472

Dnipro, , Ukraine

Synthon investigational site 464

Donetsk, , Ukraine

Synthon investigational site 468

Donetsk, , Ukraine

Synthon investigational site 495

Ivano-Frankivsk, , Ukraine

Synthon investigational site 461

Kharkiv, , Ukraine

Synthon investigational site 469

Kharkiv, , Ukraine

Synthon investigational site 455

Kyiv, , Ukraine

Synthon investigational site 456

Kyiv, , Ukraine

Synthon investigational site 496

Kyiv, , Ukraine

Synthon investigational site 473

Lutsk, , Ukraine

Synthon investigational site 462

Lviv, , Ukraine

Synthon investigational site 466

Lviv, , Ukraine

Synthon investigational site 497

Lviv, , Ukraine

Synthon investigational site 498

Mariupol, , Ukraine

Synthon investigational site 457

Odesa, , Ukraine

Synthon investigational site 470

Poltava, , Ukraine

Synthon investigational site 471

Uzhhorod, , Ukraine

Synthon investigational site 465

Vinnytsia, , Ukraine

Synthon investigational site 460

Zhytomyr, , Ukraine

Synthon investigational site 284

Sheffield, , United Kingdom

Synthon investigational site 281

Stoke-on-Trent, , United Kingdom

Synthon investigational site 283

Torquay, , United Kingdom

Synthon investigational site 280

Truro, , United Kingdom

Countries

Greece; Kazakhstan; United States; Belarus; Bosnia and Herzegovina; Bulgaria; Croatia; Czechia; Estonia; Georgia; Germany; Italy; Mexico; Moldova; Poland; Romania; Russia; Serbia; South Africa; Ukraine; United Kingdom

References

Cohen J, Belova A, Selmaj K, Wolf C, Sormani MP, Oberye J, van den Tweel E, Mulder R, Koper N, Voortman G, Barkhof F; Glatiramer Acetate Clinical Trial to Assess Equivalence With Copaxone (GATE) Study Group. Equivalence of Generic Glatiramer Acetate in Multiple Sclerosis: A Randomized Clinical Trial. JAMA Neurol. 2015 Dec;72(12):1433-41. doi: 10.1001/jamaneurol.2015.2154.

Reference Type: RESULT

PMID: 26458034 (View on PubMed)

Other Identifiers

2011-000888-27

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GTR001

Identifier Type: -

Identifier Source: org_study_id