Clinical trial NCT01489254: Efficacy and Safety of GTR in Comparison to Copaxone®
Official title: Multi-centre, Randomized, Double-blind, Placebo-controlled, Parallel-group, 9 Month, Equivalence Trial Comparing the Efficacy and Safety and Tolerability of GTR (Synthon BV) to Copaxone® (Teva) in Subjects With Relapsing Remitting Multiple Sclerosis Followed by an Open-label 15 Month GTR Treatment Part Evaluating the Long-term GTR Treatment Effects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Multiple Sclerosis
Keywords: Multiple Sclerosis,
Relapsing-Remitting Multiple Sclerosis,
glatiramer acetate,
MRI,
lesions,
MS relapse rate,
Copaxone
Lead sponsor: Synthon BV
Sponsor class: INDUSTRY
First posted: 2011-12-09
Enrollment: 794
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: The Number of T1-Gadolinium Enhancing Lesions During Months 7-9
timeFrame: 9 months
Secondary outcomes:
Other outcomes:
Locations:
city: Irvine
country: United States
facility: Synthon investigational site 112
state: California
city: Port Charlotte
country: United States
facility: Synthon investigational site 120
state: Florida
city: Sunrise
country: United States
facility: Synthon investigational site 130
state: Florida
city: Elk Grove Village
country: United States
facility: Synthon investigational site 107
state: Illinois
city: Raleigh
country: United States
facility: Synthon investigational site 141
state: North Carolina
city: Cleveland
country: United States
facility: Synthon investigational site 106
state: Ohio
city: Dayton
country: United States
facility: Synthon investigational site 135
state: Ohio
city: Bitebsk
country: Belarus
facility: Synthon investigational site 401
city: Gomel
country: Belarus
facility: Synthon investigational site 402
city: Grodno
country: Belarus
facility: Synthon investigational site 403
city: Minsk
country: Belarus
facility: Synthon investigational site 404
city: Minsk
country: Belarus
facility: Synthon investigational site 407
city: Minsk
country: Belarus
facility: Synthon investigational site 408
city: Vitebsk
country: Belarus
facility: Synthon investigational site 405
city: Banja Luka
country: Bosnia and Herzegovina
facility: Synthon investigational site 486
city: Sarajevo
country: Bosnia and Herzegovina
facility: Synthon investigational site 487
city: Tuzla
country: Bosnia and Herzegovina
facility: Synthon investigational site 488
city: Pleven
country: Bulgaria
facility: Synthon investigational site 204
city: Pleven
country: Bulgaria
facility: Synthon investigational site 207
city: Plovdiv
country: Bulgaria
facility: Synthon investigational site 206
city: Sofia
country: Bulgaria
facility: Synthon investigational site 202
city: Sofia
country: Bulgaria
facility: Synthon investigational site 203
city: Sofia
country: Bulgaria
facility: Synthon investigational site 205
city: Sofia
country: Bulgaria
facility: Synthon investigational site 208
city: Varna
country: Bulgaria
facility: Synthon investigational site 201
city: Osijek
country: Croatia
facility: Synthon investigational site 477
city: Zagreb
country: Croatia
facility: Synthon investigational site 475
city: Zagreb
country: Croatia
facility: Synthon investigational site 476
city: Zagreb
country: Croatia
facility: Synthon investigational site 478
city: Brno
country: Czech Republic
facility: Synthon investigational site 211
city: Brno
country: Czech Republic
facility: Synthon investigational site 217
city: Olomouc
country: Czech Republic
facility: Synthon investigational site 210
city: Ostrava
country: Czech Republic
facility: Synthon investigational site 212
city: Praha
country: Czech Republic
facility: Synthon investigational site 215
city: Praha
country: Czech Republic
facility: Synthon investigational site 216
city: Teplice
country: Czech Republic
facility: Synthon investigational site 214
city: Kohtla-Jarve
country: Estonia
facility: Synthon investigational site 297
city: Tallinn
country: Estonia
facility: Synthon investigational site 296
city: Tbilisi
country: Georgia
facility: Synthon investigational site 526
city: Tbilisi
country: Georgia
facility: Synthon investigational site 527
city: Tbilisi
country: Georgia
facility: Synthon investigational site 528
city: Tbilisi
country: Georgia
facility: Synthon investigational site 529
city: Tbilisi
country: Georgia
facility: Synthon investigational site 530
city: Jena
country: Germany
facility: Synthon investigational site 227
city: Coppito
country: Italy
facility: Synthon investigational site 234
city: Naples
country: Italy
facility: Synthon investigational site 235
city: Guadalajara
country: Mexico
facility: Synthon investigational site 516
city: Mexico City
country: Mexico
facility: Synthon investigational site 512
city: Mexico City
country: Mexico
facility: Synthon investigational site 514
city: Morelia
country: Mexico
facility: Synthon investigational site 515
city: Chisinau
country: Moldova, Republic of
facility: Synthon investigational site 547
city: Chisinau
country: Moldova, Republic of
facility: Synthon investigational site 548
city: Chisinau
country: Moldova, Republic of
facility: Synthon investigational site 549
city: Chisinau
country: Moldova, Republic of
facility: Synthon investigational site 550
city: Bialystok
country: Poland
facility: Synthon investigational site 244
city: Katowice
country: Poland
facility: Synthon investigational site 240
city: Katowice
country: Poland
facility: Synthon investigational site 241
city: Katowice
country: Poland
facility: Synthon investigational site 242
city: Katowice
country: Poland
facility: Synthon investigational site 245
city: Lodz
country: Poland
facility: Synthon investigational site 247
city: Lublin
country: Poland
facility: Synthon investigational site 251
city: Olsztyn
country: Poland
facility: Synthon investigational site 243
city: Poznan
country: Poland
facility: Synthon investigational site 248
city: Szczecin
country: Poland
facility: Synthon investigational site 250
city: Warszawa
country: Poland
facility: Synthon investigational site 246
city: Wroclaw
country: Poland
facility: Synthon investigational site 249
city: Bucharest
country: Romania
facility: Synthon investigational site 260
city: Bucharest
country: Romania
facility: Synthon investigational site 262
city: Bucharest
country: Romania
facility: Synthon investigational site 263
city: Bucharest
country: Romania
facility: Synthon investigational site 264
city: Bucharest
country: Romania
facility: Synthon investigational site 265
city: Cluj-Napoca
country: Romania
facility: Synthon investigational site 266
city: Timisoara
country: Romania
facility: Synthon investigational site 267
city: Arkhangelsk
country: Russian Federation
facility: Synthon investigational site 438
city: Barnaul
country: Russian Federation
facility: Synthon investigational site 435
city: Belgorod
country: Russian Federation
facility: Synthon investigational site 437
city: Ekaterinburg
country: Russian Federation
facility: Synthon investigational site 431
city: Kaluga
country: Russian Federation
facility: Synthon investigational site 445
city: Kazan
country: Russian Federation
facility: Synthon investigational site 427
city: Kemerovo
country: Russian Federation
facility: Synthon investigational site 432
city: Kirov
country: Russian Federation
facility: Synthon investigational site 447
city: Lipetsk
country: Russian Federation
facility: Synthon investigational site 446
city: Moscow
country: Russian Federation
facility: Synthon investigational site 571
city: Nizhniy Novgorod
country: Russian Federation
facility: Synthon investigational site 428
city: Nizhniy Novgorod
country: Russian Federation
facility: Synthon investigational site 429
city: Novosibirsk
country: Russian Federation
facility: Synthon investigational site 434
city: Novosibirsk
country: Russian Federation
facility: Synthon investigational site 442
city: Penza
country: Russian Federation
facility: Synthon investigational site 444
city: Pyatigorsk
country: Russian Federation
facility: Synthon investigational site 433
city: Samara
country: Russian Federation
facility: Synthon investigational site 424
city: Smolensk
country: Russian Federation
facility: Synthon investigational site 420
city: St.Petersburg
country: Russian Federation
facility: Synthon investigational site 421
city: St.Petersburg
country: Russian Federation
facility: Synthon investigational site 426
city: St.Petersburg
country: Russian Federation
facility: Synthon investigational site 430
city: St.Petersburg
country: Russian Federation
facility: Synthon investigational site 440
city: Tomsk
country: Russian Federation
facility: Synthon investigational site 422
city: Tver
country: Russian Federation
facility: Synthon investigational site 441
city: Tyumen
country: Russian Federation
facility: Synthon investigational site 425
city: Ufa
country: Russian Federation
facility: Synthon investigational site 423
city: Belgrade
country: Serbia
facility: Synthon investigational site 450
city: Belgrade
country: Serbia
facility: Synthon investigational site 451
city: Kragujevac
country: Serbia
facility: Synthon investigational site 453
city: Novi Sad
country: Serbia
facility: Synthon investigational site 452
city: Cape Town
country: South Africa
facility: Synthon investigational site 501
city: Durban
country: South Africa
facility: Synthon investigational site 505
city: Pretoria
country: South Africa
facility: Synthon investigational site 502
city: Cherkassy
country: Ukraine
facility: Synthon investigational site 474
city: Chernihiv
country: Ukraine
facility: Synthon investigational site 459
city: Chernivtsi
country: Ukraine
facility: Synthon investigational site 463
city: Dnepropetrovsk
country: Ukraine
facility: Synthon investigational site 458
city: Dnepropetrovsk
country: Ukraine
facility: Synthon investigational site 472
city: Donetsk
country: Ukraine
facility: Synthon investigational site 464
city: Donetsk
country: Ukraine
facility: Synthon investigational site 468
city: Ivano-Frankivsk
country: Ukraine
facility: Synthon investigational site 495
city: Kharkiv
country: Ukraine
facility: Synthon investigational site 461
city: Kharkiv
country: Ukraine
facility: Synthon investigational site 469
city: Kyiv
country: Ukraine
facility: Synthon investigational site 455
city: Kyiv
country: Ukraine
facility: Synthon investigational site 456
city: Kyiv
country: Ukraine
facility: Synthon investigational site 496
city: Lutsk
country: Ukraine
facility: Synthon investigational site 473
city: Lviv
country: Ukraine
facility: Synthon investigational site 462
city: Lviv
country: Ukraine
facility: Synthon investigational site 466
city: Lviv
country: Ukraine
facility: Synthon investigational site 497
city: Mariupol
country: Ukraine
facility: Synthon investigational site 498
city: Odessa
country: Ukraine
facility: Synthon investigational site 457
city: Poltava
country: Ukraine
facility: Synthon investigational site 470
city: Uzhhorod
country: Ukraine
facility: Synthon investigational site 471
city: Vinnytsia
country: Ukraine
facility: Synthon investigational site 465
city: Zhytomyr
country: Ukraine
facility: Synthon investigational site 460
city: Sheffield
country: United Kingdom
facility: Synthon investigational site 284
city: Stoke on Trent
country: United Kingdom
facility: Synthon investigational site 281
city: Torquay
country: United Kingdom
facility: Synthon investigational site 283
city: Truro
country: United Kingdom
facility: Synthon investigational site 280
Study officials:
References:
citation: 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.