Efficacy and Safety of GTR in Comparison to Copaxone®
- Conditions
- Multiple Sclerosis
- Interventions
- Registration Number
- NCT01489254
- Lead Sponsor
- Synthon BV
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 794
- 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.
-
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
-
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
-
within one year before screening:
- mitoxantrone, but subject cannot be enrolled when mitoxantrone was taken at a cumulative lifetime dosing above 100 mg/m2
-
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)
-
within 3 months before screening:
- azathioprine, methotrexate
- plasma exchange
- any other experimental intervention, in particular experimental drugs
-
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description GTR Glatiramer Acetate (GTR) Drug Copaxone® Glatiramer Acetate (Copaxone®) Drug Placebo Placebo Drug
- Primary Outcome Measures
Name Time Method The Number of T1-Gadolinium Enhancing Lesions During Months 7-9 9 months The primary endpoint was the total number of gadolinium enhancing lesions (i.e., the cumulative number of new and persisting gadolinium enhancing lesions) during months 7 through 9.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (133)
Synthon investigational site 215
🇨🇿Praha, Czech Republic
Synthon investigational site 214
🇨🇿Teplice, Czech Republic
Synthon investigational site 529
🇬🇪Tbilisi, Georgia
Synthon investigational site 263
🇷🇴Bucharest, Romania
Synthon investigational site 401
🇧🇾Bitebsk, Belarus
Synthon investigational site 112
🇺🇸Irvine, California, United States
Synthon investigational site 408
🇧🇾Minsk, Belarus
Synthon investigational site 405
🇧🇾Vitebsk, Belarus
Synthon investigational site 141
🇺🇸Raleigh, North Carolina, United States
Synthon investigational site 402
🇧🇾Gomel, Belarus
Synthon investigational site 407
🇧🇾Minsk, Belarus
Synthon investigational site 478
🇭🇷Zagreb, Croatia
Synthon investigational site 204
🇧🇬Pleven, Bulgaria
Synthon investigational site 487
🇧🇦Sarajevo, Bosnia and Herzegovina
Synthon investigational site 206
🇧🇬Plovdiv, Bulgaria
Synthon investigational site 452
🇷🇸Novi Sad, Serbia
Synthon investigational site 441
🇷🇺Tver, Russian Federation
Synthon investigational site 425
🇷🇺Tyumen, Russian Federation
Synthon investigational site 501
🇿🇦Cape Town, South Africa
Synthon investigational site 453
🇷🇸Kragujevac, Serbia
Synthon investigational site 472
🇺🇦Dnepropetrovsk, Ukraine
Synthon investigational site 495
🇺🇦Ivano-Frankivsk, Ukraine
Synthon investigational site 461
🇺🇦Kharkiv, Ukraine
Synthon investigational site 457
🇺🇦Odessa, Ukraine
Synthon investigational site 283
🇬🇧Torquay, United Kingdom
Synthon investigational site 284
🇬🇧Sheffield, United Kingdom
Synthon investigational site 458
🇺🇦Dnepropetrovsk, Ukraine
Synthon investigational site 464
🇺🇦Donetsk, Ukraine
Synthon investigational site 469
🇺🇦Kharkiv, Ukraine
Synthon investigational site 496
🇺🇦Kyiv, Ukraine
Synthon investigational site 466
🇺🇦Lviv, Ukraine
Synthon investigational site 241
🇵🇱Katowice, Poland
Synthon investigational site 280
🇬🇧Truro, United Kingdom
Synthon investigational site 130
🇺🇸Sunrise, Florida, United States
Synthon investigational site 106
🇺🇸Cleveland, Ohio, United States
Synthon investigational site 403
🇧🇾Grodno, Belarus
Synthon investigational site 404
🇧🇾Minsk, Belarus
Synthon investigational site 488
🇧🇦Tuzla, Bosnia and Herzegovina
Synthon investigational site 207
🇧🇬Pleven, Bulgaria
Synthon investigational site 205
🇧🇬Sofia, Bulgaria
Synthon investigational site 201
🇧🇬Varna, Bulgaria
Synthon investigational site 477
🇭🇷Osijek, Croatia
Synthon investigational site 476
🇭🇷Zagreb, Croatia
Synthon investigational site 217
🇨🇿Brno, Czech Republic
Synthon investigational site 211
🇨🇿Brno, Czech Republic
Synthon investigational site 210
🇨🇿Olomouc, Czech Republic
Synthon investigational site 212
🇨🇿Ostrava, Czech Republic
Synthon investigational site 216
🇨🇿Praha, Czech Republic
Synthon investigational site 297
🇪🇪Kohtla-Jarve, Estonia
Synthon investigational site 296
🇪🇪Tallinn, Estonia
Synthon investigational site 526
🇬🇪Tbilisi, Georgia
Synthon investigational site 528
🇬🇪Tbilisi, Georgia
Synthon investigational site 234
🇮🇹Coppito, Italy
Synthon investigational site 235
🇮🇹Naples, Italy
Synthon investigational site 227
🇩🇪Jena, Germany
Synthon investigational site 530
🇬🇪Tbilisi, Georgia
Synthon investigational site 512
🇲🇽Mexico City, Mexico
Synthon investigational site 514
🇲🇽Mexico City, Mexico
Synthon investigational site 547
🇲🇩Chisinau, Moldova, Republic of
Synthon investigational site 548
🇲🇩Chisinau, Moldova, Republic of
Synthon investigational site 549
🇲🇩Chisinau, Moldova, Republic of
Synthon investigational site 550
🇲🇩Chisinau, Moldova, Republic of
Synthon investigational site 244
🇵🇱Bialystok, Poland
Synthon investigational site 242
🇵🇱Katowice, Poland
Synthon investigational site 245
🇵🇱Katowice, Poland
Synthon investigational site 247
🇵🇱Lodz, Poland
Synthon investigational site 248
🇵🇱Poznan, Poland
Synthon investigational site 250
🇵🇱Szczecin, Poland
Synthon investigational site 260
🇷🇴Bucharest, Romania
Synthon investigational site 262
🇷🇴Bucharest, Romania
Synthon investigational site 249
🇵🇱Wroclaw, Poland
Synthon investigational site 435
🇷🇺Barnaul, Russian Federation
Synthon investigational site 264
🇷🇴Bucharest, Romania
Synthon investigational site 266
🇷🇴Cluj-Napoca, Romania
Synthon investigational site 265
🇷🇴Bucharest, Romania
Synthon investigational site 438
🇷🇺Arkhangelsk, Russian Federation
Synthon investigational site 267
🇷🇴Timisoara, Romania
Synthon investigational site 437
🇷🇺Belgorod, Russian Federation
Synthon investigational site 431
🇷🇺Ekaterinburg, Russian Federation
Synthon investigational site 445
🇷🇺Kaluga, Russian Federation
Synthon investigational site 450
🇷🇸Belgrade, Serbia
Synthon investigational site 427
🇷🇺Kazan, Russian Federation
Synthon investigational site 447
🇷🇺Kirov, Russian Federation
Synthon investigational site 571
🇷🇺Moscow, Russian Federation
Synthon investigational site 446
🇷🇺Lipetsk, Russian Federation
Synthon investigational site 428
🇷🇺Nizhniy Novgorod, Russian Federation
Synthon investigational site 429
🇷🇺Nizhniy Novgorod, Russian Federation
Synthon investigational site 434
🇷🇺Novosibirsk, Russian Federation
Synthon investigational site 444
🇷🇺Penza, Russian Federation
Synthon investigational site 433
🇷🇺Pyatigorsk, Russian Federation
Synthon investigational site 420
🇷🇺Smolensk, Russian Federation
Synthon investigational site 421
🇷🇺St.Petersburg, Russian Federation
Synthon investigational site 426
🇷🇺St.Petersburg, Russian Federation
Synthon investigational site 430
🇷🇺St.Petersburg, Russian Federation
Synthon investigational site 422
🇷🇺Tomsk, Russian Federation
Synthon investigational site 440
🇷🇺St.Petersburg, Russian Federation
Synthon investigational site 423
🇷🇺Ufa, Russian Federation
Synthon investigational site 451
🇷🇸Belgrade, Serbia
Synthon investigational site 502
🇿🇦Pretoria, South Africa
Synthon investigational site 474
🇺🇦Cherkassy, Ukraine
Synthon investigational site 459
🇺🇦Chernihiv, Ukraine
Synthon investigational site 505
🇿🇦Durban, South Africa
Synthon investigational site 468
🇺🇦Donetsk, Ukraine
Synthon investigational site 463
🇺🇦Chernivtsi, Ukraine
Synthon investigational site 456
🇺🇦Kyiv, Ukraine
Synthon investigational site 455
🇺🇦Kyiv, Ukraine
Synthon investigational site 497
🇺🇦Lviv, Ukraine
Synthon investigational site 473
🇺🇦Lutsk, Ukraine
Synthon investigational site 462
🇺🇦Lviv, Ukraine
Synthon investigational site 498
🇺🇦Mariupol, 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 281
🇬🇧Stoke on Trent, United Kingdom
Synthon investigational site 202
🇧🇬Sofia, Bulgaria
Synthon investigational site 135
🇺🇸Dayton, Ohio, United States
Synthon investigational site 208
🇧🇬Sofia, Bulgaria
Synthon investigational site 107
🇺🇸Elk Grove Village, Illinois, United States
Synthon investigational site 120
🇺🇸Port Charlotte, Florida, United States
Synthon investigational site 203
🇧🇬Sofia, Bulgaria
Synthon investigational site 432
🇷🇺Kemerovo, Russian Federation
Synthon investigational site 442
🇷🇺Novosibirsk, Russian Federation
Synthon investigational site 424
🇷🇺Samara, Russian Federation
Synthon investigational site 515
🇲🇽Morelia, Mexico
Synthon investigational site 527
🇬🇪Tbilisi, Georgia
Synthon investigational site 486
🇧🇦Banja Luka, Bosnia and Herzegovina
Synthon investigational site 475
🇭🇷Zagreb, Croatia
Synthon investigational site 516
🇲🇽Guadalajara, Mexico
Synthon investigational site 251
🇵🇱Lublin, Poland
Synthon investigational site 246
🇵🇱Warszawa, Poland
Synthon investigational site 243
🇵🇱Olsztyn, Poland
Synthon investigational site 240
🇵🇱Katowice, Poland