Efficacy and Safety of GTR in Comparison to Copaxone®

Multiple Sclerosis Clinical Trial

— GATE  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01489254
• Other study ID #: GTR001
• Secondary ID: 2011-000888-27
• Status: Completed
• Phase: Phase 3
• First received: December 8, 2011
• Last updated: March 18, 2015
• Start date: October 2011
• Est. completion date: January 2015

Study information

• Verified date: June 2014
• Source: Synthon BV
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardUnited States: Food and Drug AdministrationBelarus: Ministry of Health of the Republic of BelarusBelarus: Local Ethics CommitteesBosnia and Herzegovina: Medicines and Medical Devices AgencyBosnia and Herzegovina: Ethics Committees at Medical sitesBulgaria: Bulgarian Drug AgencyBulgaria: Ethics Committee for Multicenter Clinical TrialsCroatia: Ministry of HealthCroatia: Central Ethics CommitteeCzech Republic: State Institute for Drug Control (SUKL)Czech Republic: Multicenter Ethics CommitteeEstonia: State Agency of MedicinesEstonia: Central Ethics CommitteeGeorgia: Ministry of Labour, Health and Social AffairsGeorgia: Ethics Committees at Medical sitesGermany: Federal Agency for Medicinal Products and Medical Devices (BfArM)Germany: Regional Independent Ethics CommitteeItaly: Regulatory Authority at Medical SiteItaly: Ethics Committee at Medical siteMexico: Federal Commission for Protection against Sanitary RisksMexico: Ethics Committees at Medical sitesMoldova: Medicine AgencyMoldova: National Ethics CommitteePoland: Central Register of clinical trialsPoland: Multicenter Ethics CommitteeRomania: National Medicine and Medical Devices AgencyRomania: National Ethics CommitteeRussia: Ministry of Healthcare and Social Development of the Russian FederationSerbia: Medicines and Medical Devices AgencySerbia: Ethics Committees at Medical SitesSouth Africa: Medicines Control Council (MCC)South Africa: Ethics Committees at Medical sitesUK: The Medicines and Healthcare products Regulatory AgencyUK: Regional Independent Ethics CommitteeUkraine: State Expert Centre under the Ministry of Health of UkraineUkraine: Central Ethics Committee
• Study type: Interventional

Clinical Trial 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

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 information / eligibility

• Status: Completed
• Enrollment: 794
• Est. completion date: January 2015
• Est. primary completion date: January 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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-ß 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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Relapsing-Remitting
• Sclerosis

Intervention

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

Locations

Country	Name	City	State
Belarus	Synthon investigational site 401	Bitebsk
Belarus	Synthon investigational site 402	Gomel
Belarus	Synthon investigational site 403	Grodno
Belarus	Synthon investigational site 404	Minsk
Belarus	Synthon investigational site 407	Minsk
Belarus	Synthon investigational site 408	Minsk
Belarus	Synthon investigational site 405	Vitebsk
Bosnia and Herzegovina	Synthon investigational site 486	Banja Luka
Bosnia and Herzegovina	Synthon investigational site 487	Sarajevo
Bosnia and Herzegovina	Synthon investigational site 488	Tuzla
Bulgaria	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
Croatia	Synthon investigational site 477	Osijek
Croatia	Synthon investigational site 475	Zagreb
Croatia	Synthon investigational site 476	Zagreb
Croatia	Synthon investigational site 478	Zagreb
Czech Republic	Synthon investigational site 211	Brno
Czech Republic	Synthon investigational site 217	Brno
Czech Republic	Synthon investigational site 210	Olomouc
Czech Republic	Synthon investigational site 212	Ostrava
Czech Republic	Synthon investigational site 215	Praha
Czech Republic	Synthon investigational site 216	Praha
Czech Republic	Synthon investigational site 214	Teplice
Estonia	Synthon investigational site 297	Kohtla-Jarve
Estonia	Synthon investigational site 296	Tallinn
Georgia	Synthon investigational site 526	Tbilisi
Georgia	Synthon investigational site 527	Tbilisi
Georgia	Synthon investigational site 528	Tbilisi
Georgia	Synthon investigational site 529	Tbilisi
Georgia	Synthon investigational site 530	Tbilisi
Germany	Synthon investigational site 227	Jena
Italy	Synthon investigational site 234	Coppito
Italy	Synthon investigational site 235	Naples
Mexico	Synthon investigational site 516	Guadalajara
Mexico	Synthon investigational site 512	Mexico City
Mexico	Synthon investigational site 514	Mexico City
Mexico	Synthon investigational site 515	Morelia
Moldova, Republic of	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
Poland	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	Synthon investigational site 247	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	Warszawa
Poland	Synthon investigational site 249	Wroclaw
Romania	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	Timisoara
Russian Federation	Synthon investigational site 438	Arkhangelsk
Russian Federation	Synthon investigational site 435	Barnaul
Russian Federation	Synthon investigational site 437	Belgorod
Russian Federation	Synthon investigational site 431	Ekaterinburg
Russian Federation	Synthon investigational site 445	Kaluga
Russian Federation	Synthon investigational site 427	Kazan
Russian Federation	Synthon investigational site 432	Kemerovo
Russian Federation	Synthon investigational site 447	Kirov
Russian Federation	Synthon investigational site 446	Lipetsk
Russian Federation	Synthon investigational site 571	Moscow
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 442	Novosibirsk
Russian Federation	Synthon investigational site 444	Penza
Russian Federation	Synthon investigational site 433	Pyatigorsk
Russian Federation	Synthon investigational site 424	Samara
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 440	St.Petersburg
Russian Federation	Synthon investigational site 422	Tomsk
Russian Federation	Synthon investigational site 441	Tver
Russian Federation	Synthon investigational site 425	Tyumen
Russian Federation	Synthon investigational site 423	Ufa
Serbia	Synthon investigational site 450	Belgrade
Serbia	Synthon investigational site 451	Belgrade
Serbia	Synthon investigational site 453	Kragujevac
Serbia	Synthon investigational site 452	Novi Sad
South Africa	Synthon investigational site 501	Cape Town
South Africa	Synthon investigational site 505	Durban
South Africa	Synthon investigational site 502	Pretoria
Ukraine	Synthon investigational site 474	Cherkassy
Ukraine	Synthon investigational site 459	Chernihiv
Ukraine	Synthon investigational site 463	Chernivtsi
Ukraine	Synthon investigational site 458	Dnepropetrovsk
Ukraine	Synthon investigational site 472	Dnepropetrovsk
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	Odessa
Ukraine	Synthon investigational site 470	Poltava
Ukraine	Synthon investigational site 471	Uzhhorod
Ukraine	Synthon investigational site 465	Vinnytsia
Ukraine	Synthon investigational site 460	Zhytomyr
United Kingdom	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 States	Synthon investigational site 106	Cleveland	Ohio
United States	Synthon investigational site 135	Dayton	Ohio
United States	Synthon investigational site 107	Elk Grove Village	Illinois
United States	Synthon investigational site 112	Irvine	California
United States	Synthon investigational site 120	Port Charlotte	Florida
United States	Synthon investigational site 141	Raleigh	North Carolina
United States	Synthon investigational site 130	Sunrise	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Synthon BV

Countries where clinical trial is conducted

United States,  Belarus,  Bosnia and Herzegovina,  Bulgaria,  Croatia,  Czech Republic,  Estonia,  Georgia,  Germany,  Italy,  Mexico,  Moldova, Republic of,  Poland,  Romania,  Russian Federation,  Serbia,  South Africa,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The number of Gadolinium enhancing lesions during months 7-9		9 months	No