An Efficacy, Safety and Tolerability Study of Glatiramer Acetate (GA) 20 mg/0.5 ml New Formulation Administered Daily by Subcutaneous (SC) Injection in Subjects With Relapsing-Remitting Multiple Sclerosis (RRMS)

Relapsing-Remitting Multiple Sclerosis Clinical Trial

— GLOW  

Official title:

A Multinational, Multicenter, Randomized, Parallel Group, Double Blind, Placebo Controlled Study Performed in Subjects With Relapsing-Remitting Multiple Sclerosis to Assess the Efficacy, Safety and Tolerability of Glatiramer Acetate 20mg/0.5ml New Formulation Administered Daily by Subcutaneous Injection

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01578785
• Other study ID #: GA-MS-302
• Secondary ID: 2011-005550-57
• Status: Terminated
• Phase: Phase 3
• First received: March 13, 2012
• Last updated: February 19, 2014
• Start date: March 2012
• Est. completion date: November 2012

Study information

• Verified date: February 2014
• Source: Teva Pharmaceutical Industries
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This study will investigate the efficacy, safety and tolerability of a new formulation of glatiramer acetate administered at 20 mg/0.5 ml daily versus placebo in patients with Relapsing-Remitting Multiple Sclerosis (RRMS).

Description:

Approximately 1400 participants were planned for this study, however only 178 were enrolled prior to early termination.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 178
• Est. completion date: November 2012
• Est. primary completion date: October 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

Subjects must meet all inclusion criteria in order to be eligible for the study:

• Subjects must have a confirmed and documented multiple sclerosis (MS) diagnosis as defined by the 2010 Revised McDonald criteria [Ann Neurol 2011: 69:292-302], with a relapsing-remitting disease course.

• Subjects must be ambulatory with a Kurtzke's Expanded Disability Status Scale (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 by mouth (PO)] or ACTH (adrenocorticotropic hormone) 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,

• At least two documented relapses in the 24 months prior to screening,

• One documented relapse between 12 and 24 months prior to screening with at least one documented T1-Gd enhancing lesion in a magnetic resonance imaging (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 [acceptable methods of birth control in this study include: surgical sterilization, intrauterine devices, oral contraceptive, contraceptive patch, long-acting injectable contraceptive, partner's vasectomy or a double-barrier method (condom or diaphragm with spermicide)].

• 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.

Exclusion Criteria:

Any of the following conditions will exclude the subject from entering the study:

• 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 agents (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 IFNß 1a and 1b, and IV Immunoglobulin (IVIg)] within 2 months prior to screening.

• Previous use of glatiramer acetate (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.

• Glomerular filtration rate (GFR) = 60 mL/minute at the screening visit

• Inability to successfully undergo MRI scanning.

• A known drug hypersensitivity to Mannitol.

• Subjects who underwent endovascular treatment for chronic cerebrospinal venous insufficiency (CCSVI).

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
• Relapsing-Remitting Multiple Sclerosis
• Sclerosis

Intervention

Drug:
• Glatiramer Acetate
Glatiramer acetate 20mg in 0.5ml for subcutaneous injection in a pre-filled syringe (PFS) is administered daily. Each PFS also contains 20mg mannitol dissolved in water for injection.
• Placebo
Matching placebo injection; 20 mg mannitol dissolved in 0.5 mL water for subcutaneous injection in a PFS is administered daily.

Locations

Country	Name	City	State
Albania	Teva Investigational Site 67001	Tirana
Belarus	Teva Investigational Site 68007	Gomel
Belarus	Teva Investigational Site 68004	Grodno
Belarus	Teva Investigational Site 68003	Minsk
Belarus	Teva Investigational Site 68005	Minsk
Belarus	Teva Investigational Site 68006	Minsk
Belarus	Teva Investigational Site 68001	Vitebsk
Belarus	Teva Investigational Site 68002	Vitebsk
Bosnia and Herzegovina	Teva Investigational Site 69004	Bihac
Bosnia and Herzegovina	Teva Investigational Site 69002	Mostar
Bosnia and Herzegovina	Teva Investigational Site 69001	Sarajevo
Bosnia and Herzegovina	Teva Investigational Site 69003	Tuzla
Bulgaria	Teva Investigational Site 59020	Blagoevgrad
Bulgaria	Teva Investigational Site 59018	Pleven
Bulgaria	Teva Investigational Site 59019	Pleven
Bulgaria	Teva Investigational Site 59025	Pleven
Bulgaria	Teva Investigational Site 59024	Ruse
Bulgaria	Teva Investigational Site 59023	Shumen
Bulgaria	Teva Investigational Site 59006	Sofia
Bulgaria	Teva Investigational Site 59007	Sofia
Bulgaria	Teva Investigational Site 59008	Sofia
Bulgaria	Teva Investigational Site 59009	Sofia
Bulgaria	Teva Investigational Site 59010	Sofia
Bulgaria	Teva Investigational Site 59011	Sofia
Bulgaria	Teva Investigational Site 59012	Sofia
Bulgaria	Teva Investigational Site 59014	Sofia
Bulgaria	Teva Investigational Site 59015	Sofia
Bulgaria	Teva Investigational Site 59016	Sofia
Bulgaria	Teva Investigational Site 59017	Sofia
Bulgaria	Teva Investigational Site 59021	Sofia
Bulgaria	Teva Investigational Site 59026	Sofia
Bulgaria	Teva Investigational Site 59022	Stara Zagora
Bulgaria	Teva Investigational Site 59013	Varna
Bulgaria	Teva Investigational Site 59027	Veliko Tarnovo
Bulgaria	Teva Investigational Site 59028	Veliko Tarnovo
Croatia	Teva Investigational Site 60003	Osijek
Croatia	Teva Investigational Site 60005	Varazdin
Croatia	Teva Investigational Site 60001	Zagreb
Croatia	Teva Investigational Site 60002	Zagreb
Croatia	Teva Investigational Site 60004	Zagreb
Croatia	Teva Investigational Site 60006	Zagreb
Croatia	Teva Investigational Site 60007	Zagreb
Estonia	Teva Investigational Site 55004	Paernu
Estonia	Teva Investigational Site 55003	Tallinn
Georgia	Teva Investigational Site 81001	Tbilisi
Georgia	Teva Investigational Site 81002	Tbilisi
Georgia	Teva Investigational Site 81003	Tbilisi
Georgia	Teva Investigational Site 81004	Tbilisi
Georgia	Teva Investigational Site 81005	Tbilisi
Greece	Teva Investigational Site 63017	Athens
Greece	Teva Investigational Site 63021	Athens
Greece	Teva Investigational Site 63020	Melissia
Greece	Teva Investigational Site 63018	Thessaloniki
Greece	Teva Investigational Site 63019	Thessaloniki
Latvia	Teva Investigational Site 56004	Riga
Macedonia, The Former Yugoslav R	Teva Investigational Site 65005	Shtip
Macedonia, The Former Yugoslav R	Teva Investigational Site 65001	Skopje
Macedonia, The Former Yugoslav R	Teva Investigational Site 65002	Skopje
Macedonia, The Former Yugoslav R	Teva Investigational Site 65003	Skopje
Macedonia, The Former Yugoslav R	Teva Investigational Site 65006	Strumica
Macedonia, The Former Yugoslav R	Teva Investigational Site 65004	Tetovo
Mexico	Teva Investigational Site 21023	Estado de Mexico
Mexico	Teva Investigational Site 21021	Guadalajara, JALISCO
Mexico	Teva Investigational Site 21022	Mexico City, DISTRITO FEDERAL
Mexico	Teva Investigational Site 21025	Monterrey
Mexico	Teva Investigational Site 21020	Morelia, MICHOACAN
Mexico	Teva Investigational Site 21024	San Luís Potosí
Moldova, Republic of	Teva Investigational Site 70001	Chisinau
Moldova, Republic of	Teva Investigational Site 70002	Chisinau
Moldova, Republic of	Teva Investigational Site 70003	Chisinau
Moldova, Republic of	Teva Investigational Site 70004	Chisinau
Montenegro	Teva Investigational Site 66001	Podgorica
Poland	Teva Investigational Site 53033	Bialystok
Poland	Teva Investigational Site 53020	Czestochowa
Poland	Teva Investigational Site 53023	Gdansk
Poland	Teva Investigational Site 53024	Gdansk
Poland	Teva Investigational Site 53031	Grodzisk Mazowiecki
Poland	Teva Investigational Site 53032	Grodzisk Mazowiecki
Poland	Teva Investigational Site 53021	Katowice
Poland	Teva Investigational Site 53019	Kielce
Poland	Teva Investigational Site 53028	Konstancin-Jeziorna
Poland	Teva Investigational Site 53037	Koscierzyna
Poland	Teva Investigational Site 53018	Lodz
Poland	Teva Investigational Site 53027	Lublin
Poland	Teva Investigational Site 53036	Olsztyn
Poland	Teva Investigational Site 53034	Poznan
Poland	Teva Investigational Site 53030	Poznan / Plewiska
Poland	Teva Investigational Site 53025	Szczecin
Poland	Teva Investigational Site 53026	Szczecin
Poland	Teva Investigational Site 53022	Warsaw
Poland	Teva Investigational Site 53029	Warszawa
Romania	Teva Investigational Site 52010	Bucuresti
Romania	Teva Investigational Site 52012	Bucuresti
Romania	Teva Investigational Site 52015	Cluj-Napoca
Romania	Teva Investigational Site 52016	Cluj-Napoca
Romania	Teva Investigational Site 52017	Constanta
Romania	Teva Investigational Site 52018	Constanta
Romania	Teva Investigational Site 52014	Iasi
Romania	Teva Investigational Site 52021	Oradea
Romania	Teva Investigational Site 52011	Piatra-Neamt
Romania	Teva Investigational Site 52013	Sibiu
Romania	Teva Investigational Site 52020	Targu-Mures
Romania	Teva Investigational Site 52019	Timisoara
Russian Federation	Teva Investigational Site 50023	Barnaul
Russian Federation	Teva Investigational Site 50021	Chelyabinsk
Russian Federation	Teva Investigational Site 50025	Kazan
Russian Federation	Teva Investigational Site 50039	Krasnodar
Russian Federation	Teva Investigational Site 50022	Moscow
Russian Federation	Teva Investigational Site 50034	Moscow
Russian Federation	Teva Investigational Site 50035	Moscow
Russian Federation	Teva Investigational Site 50036	Moscow
Russian Federation	Teva Investigational Site 50020	Nizhny Novgorod
Russian Federation	Teva Investigational Site 50024	Nizhny Novgorod
Russian Federation	Teva Investigational Site 50123	Nizhny Novgorod
Russian Federation	Teva Investigational Site 50027	Novosibirsk
Russian Federation	Teva Investigational Site 50019	Perm
Russian Federation	Teva Investigational Site 50038	Rostov-on-Don
Russian Federation	Teva Investigational Site 50032	Saint Petersburg
Russian Federation	Teva Investigational Site 50030	Samara
Russian Federation	Teva Investigational Site 50037	Saratov
Russian Federation	Teva Investigational Site 50028	Smolensk
Russian Federation	Teva Investigational Site 50029	St. Petersburg
Russian Federation	Teva Investigational Site 50031	Tyumen
Russian Federation	Teva Investigational Site 50026	Ufa
Russian Federation	Teva Investigational Site 50040	Volgograd
Russian Federation	Teva Investigational Site 50033	Yaroslavl
Serbia	Teva Investigational Site 61002	Belgrade
Serbia	Teva Investigational Site 61005	Belgrade
Serbia	Teva Investigational Site 61001	Kragujevac
Serbia	Teva Investigational Site 61003	Nis
Ukraine	Teva Investigational Site 58022	Chernihiv
Ukraine	Teva Investigational Site 58030	Donetsk
Ukraine	Teva Investigational Site 58020	Ivano-Frankivsk
Ukraine	Teva Investigational Site 58028	Kharkiv
Ukraine	Teva Investigational Site 58023	Kyiv
Ukraine	Teva Investigational Site 58025	Kyiv
Ukraine	Teva Investigational Site 58018	Lviv
Ukraine	Teva Investigational Site 58021	Odessa
Ukraine	Teva Investigational Site 58029	Poltava
Ukraine	Teva Investigational Site 58032	Simferopol, AR Crimea
Ukraine	Teva Investigational Site 58031	Uzhgorod
Ukraine	Teva Investigational Site 58027	Vinnytsya
Ukraine	Teva Investigational Site 58019	Zaporizhzhya
Ukraine	Teva Investigational Site 58024	Zaporizhzhya
United States	Teva Investigational Site 10194	Akron	Ohio
United States	Teva Investigational Site 10196	Centennial	Colorado
United States	Teva Investigational Site 10198	Charlotte	North Carolina
United States	Teva Investigational Site 10181	Chicago	Illinois
United States	Teva Investigational Site 10206	Cordova	Tennessee
United States	Teva Investigational Site 10214	Cordova	Tennessee
United States	Teva Investigational Site 10192	Cullman	Alabama
United States	Teva Investigational Site 10191	Dayton	Ohio
United States	Teva Investigational Site 10204	Fresno	California
United States	Teva Investigational Site 10203	Hickory	North Carolina
United States	Teva Investigational Site 10209	Hickory	North Carolina
United States	Teva Investigational Site 10201	La Jolla	California
United States	Teva Investigational Site 10184	Miami	Florida
United States	Teva Investigational Site 10186	Nashville	Tennessee
United States	Teva Investigational Site 10202	Northbrook	Illinois
United States	Teva Investigational Site 10188	Patchogue	New York
United States	Teva Investigational Site 10212	Raleigh	North Carolina
United States	Teva Investigational Site 10180	Sarasota	Florida
United States	Teva Investigational Site 10197	Sarasota	Florida
United States	Teva Investigational Site 10190	Tampa	Florida
United States	Teva Investigational Site 10207	Tampa	Florida
United States	Teva Investigational Site 10200	Uniontown	Ohio
United States	Teva Investigational Site 10199	Vero Beach	Florida
United States	Teva Investigational Site 10215	Winston Salem	North Carolina
United States	Teva Investigational Site 10213	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Teva Pharmaceutical Industries

Countries where clinical trial is conducted

United States,  Albania,  Belarus,  Bosnia and Herzegovina,  Bulgaria,  Croatia,  Estonia,  Georgia,  Greece,  Latvia,  Macedonia, The Former Yugoslav Republic of,  Mexico,  Moldova, Republic of,  Montenegro,  Poland,  Romania,  Russian Federation,  Serbia,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The Annualized Relapse Rate During the Placebo Controlled Period	The total number of confirmed relapses during the placebo-controlled phase is divided by the sum of the number of days on study in the placebo-controlled phase and then multiplied by the number of days in the year to calculate the annualized relapse rate.	Day 1 up to Month 12	No
Secondary	The Cumulative Number of New or Enlarging T2 Lesions Measured at Months 6 and 12 (End of Placebo Controlled Period)	Inflammatory disease activity was assessed by magnetic resonance imaging (MRI) measurement of the number of new or newly enlarged T2 lesions.	Day 1 up to Month 12	No
Secondary	The Cumulative Number of Gadolinium-enhancing Lesions on T1-weighted Images Measured at Months 6 and 12 (End of Placebo Controlled Period)	Inflammatory disease activity was assessed by magnetic resonance imaging (MRI) measurement of the number of gadolinium-enhanced T1 lesions.	Day 1 up to Month 12	No
Secondary	Percent Change From Baseline to Month 12 (End of Placebo Controlled Period) in Brain Volume	Brain atrophy was defined by the percent brain volume change from baseline to Month 12	Day 1 up to Month 12	No