Clinical trial NCT01578785: 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)
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Relapsing-Remitting Multiple Sclerosis
Lead sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
Sponsor class: INDUSTRY
First posted: 2012-04-17
Enrollment: 178
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: 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).

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

Eligibility criteria: 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 \[including IFNβ 1a and 1b, and IV Immunoglobulin (IVIg)\] 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).

Primary outcomes:
measure: The Annualized Relapse Rate During the Placebo Controlled Period
timeFrame: Day 1 up to Month 12
Secondary outcomes:
measure: The Cumulative Number of New or Enlarging T2 Lesions Measured at Months 6 and 12 (End of Placebo Controlled Period)
timeFrame: Day 1 up to Month 12
measure: The Cumulative Number of Gadolinium-enhancing Lesions on T1-weighted Images Measured at Months 6 and 12 (End of Placebo Controlled Period)
timeFrame: Day 1 up to Month 12
measure: Percent Change From Baseline to Month 12 (End of Placebo Controlled Period) in Brain Volume
timeFrame: Day 1 up to Month 12
Other outcomes:
Locations:
city: Cullman
country: United States
facility: Teva Investigational Site 10192
state: Alabama
city: Fresno
country: United States
facility: Teva Investigational Site 10204
state: California
city: La Jolla
country: United States
facility: Teva Investigational Site 10201
state: California
city: Centennial
country: United States
facility: Teva Investigational Site 10196
state: Colorado
city: Miami
country: United States
facility: Teva Investigational Site 10184
state: Florida
city: Sarasota
country: United States
facility: Teva Investigational Site 10180
state: Florida
city: Sarasota
country: United States
facility: Teva Investigational Site 10197
state: Florida
city: Tampa
country: United States
facility: Teva Investigational Site 10190
state: Florida
city: Tampa
country: United States
facility: Teva Investigational Site 10207
state: Florida
city: Vero Beach
country: United States
facility: Teva Investigational Site 10199
state: Florida
city: Chicago
country: United States
facility: Teva Investigational Site 10181
state: Illinois
city: Northbrook
country: United States
facility: Teva Investigational Site 10202
state: Illinois
city: Patchogue
country: United States
facility: Teva Investigational Site 10188
state: New York
city: Charlotte
country: United States
facility: Teva Investigational Site 10198
state: North Carolina
city: Hickory
country: United States
facility: Teva Investigational Site 10203
state: North Carolina
city: Hickory
country: United States
facility: Teva Investigational Site 10209
state: North Carolina
city: Raleigh
country: United States
facility: Teva Investigational Site 10212
state: North Carolina
city: Winston Salem
country: United States
facility: Teva Investigational Site 10215
state: North Carolina
city: Winston-Salem
country: United States
facility: Teva Investigational Site 10213
state: North Carolina
city: Akron
country: United States
facility: Teva Investigational Site 10194
state: Ohio
city: Dayton
country: United States
facility: Teva Investigational Site 10191
state: Ohio
city: Uniontown
country: United States
facility: Teva Investigational Site 10200
state: Ohio
city: Cordova
country: United States
facility: Teva Investigational Site 10206
state: Tennessee
city: Cordova
country: United States
facility: Teva Investigational Site 10214
state: Tennessee
city: Nashville
country: United States
facility: Teva Investigational Site 10186
state: Tennessee
city: Tirana
country: Albania
facility: Teva Investigational Site 67001
city: Gomel
country: Belarus
facility: Teva Investigational Site 68007
city: Grodno
country: Belarus
facility: Teva Investigational Site 68004
city: Minsk
country: Belarus
facility: Teva Investigational Site 68003
city: Minsk
country: Belarus
facility: Teva Investigational Site 68005
city: Minsk
country: Belarus
facility: Teva Investigational Site 68006
city: Vitebsk
country: Belarus
facility: Teva Investigational Site 68001
city: Vitebsk
country: Belarus
facility: Teva Investigational Site 68002
city: Bihac
country: Bosnia and Herzegovina
facility: Teva Investigational Site 69004
city: Mostar
country: Bosnia and Herzegovina
facility: Teva Investigational Site 69002
city: Sarajevo
country: Bosnia and Herzegovina
facility: Teva Investigational Site 69001
city: Tuzla
country: Bosnia and Herzegovina
facility: Teva Investigational Site 69003
city: Blagoevgrad
country: Bulgaria
facility: Teva Investigational Site 59020
city: Pleven
country: Bulgaria
facility: Teva Investigational Site 59018
city: Pleven
country: Bulgaria
facility: Teva Investigational Site 59019
city: Pleven
country: Bulgaria
facility: Teva Investigational Site 59025
city: Ruse
country: Bulgaria
facility: Teva Investigational Site 59024
city: Shumen
country: Bulgaria
facility: Teva Investigational Site 59023
city: Sofia
country: Bulgaria
facility: Teva Investigational Site 59006
city: Sofia
country: Bulgaria
facility: Teva Investigational Site 59007
city: Sofia
country: Bulgaria
facility: Teva Investigational Site 59008
city: Sofia
country: Bulgaria
facility: Teva Investigational Site 59009
city: Sofia
country: Bulgaria
facility: Teva Investigational Site 59010
city: Sofia
country: Bulgaria
facility: Teva Investigational Site 59011
city: Sofia
country: Bulgaria
facility: Teva Investigational Site 59012
city: Sofia
country: Bulgaria
facility: Teva Investigational Site 59014
city: Sofia
country: Bulgaria
facility: Teva Investigational Site 59015
city: Sofia
country: Bulgaria
facility: Teva Investigational Site 59016
city: Sofia
country: Bulgaria
facility: Teva Investigational Site 59017
city: Sofia
country: Bulgaria
facility: Teva Investigational Site 59021
city: Sofia
country: Bulgaria
facility: Teva Investigational Site 59026
city: Stara Zagora
country: Bulgaria
facility: Teva Investigational Site 59022
city: Varna
country: Bulgaria
facility: Teva Investigational Site 59013
city: Veliko Tarnovo
country: Bulgaria
facility: Teva Investigational Site 59027
city: Veliko Tarnovo
country: Bulgaria
facility: Teva Investigational Site 59028
city: Osijek
country: Croatia
facility: Teva Investigational Site 60003
city: Varazdin
country: Croatia
facility: Teva Investigational Site 60005
city: Zagreb
country: Croatia
facility: Teva Investigational Site 60001
city: Zagreb
country: Croatia
facility: Teva Investigational Site 60002
city: Zagreb
country: Croatia
facility: Teva Investigational Site 60004
city: Zagreb
country: Croatia
facility: Teva Investigational Site 60006
city: Zagreb
country: Croatia
facility: Teva Investigational Site 60007
city: Paernu
country: Estonia
facility: Teva Investigational Site 55004
city: Tallinn
country: Estonia
facility: Teva Investigational Site 55003
city: Tbilisi
country: Georgia
facility: Teva Investigational Site 81001
city: Tbilisi
country: Georgia
facility: Teva Investigational Site 81002
city: Tbilisi
country: Georgia
facility: Teva Investigational Site 81003
city: Tbilisi
country: Georgia
facility: Teva Investigational Site 81004
city: Tbilisi
country: Georgia
facility: Teva Investigational Site 81005
city: Athens
country: Greece
facility: Teva Investigational Site 63017
city: Athens
country: Greece
facility: Teva Investigational Site 63021
city: Melissia
country: Greece
facility: Teva Investigational Site 63020
city: Thessaloniki
country: Greece
facility: Teva Investigational Site 63018
city: Thessaloniki
country: Greece
facility: Teva Investigational Site 63019
city: Riga
country: Latvia
facility: Teva Investigational Site 56004
city: Shtip
country: Macedonia, The Former Yugoslav Republic of
facility: Teva Investigational Site 65005
city: Skopje
country: Macedonia, The Former Yugoslav Republic of
facility: Teva Investigational Site 65001
city: Skopje
country: Macedonia, The Former Yugoslav Republic of
facility: Teva Investigational Site 65002
city: Skopje
country: Macedonia, The Former Yugoslav Republic of
facility: Teva Investigational Site 65003
city: Strumica
country: Macedonia, The Former Yugoslav Republic of
facility: Teva Investigational Site 65006
city: Tetovo
country: Macedonia, The Former Yugoslav Republic of
facility: Teva Investigational Site 65004
city: Estado de Mexico
country: Mexico
facility: Teva Investigational Site 21023
city: Guadalajara, JALISCO
country: Mexico
facility: Teva Investigational Site 21021
city: Mexico City, DISTRITO FEDERAL
country: Mexico
facility: Teva Investigational Site 21022
city: Monterrey
country: Mexico
facility: Teva Investigational Site 21025
city: Morelia, MICHOACAN
country: Mexico
facility: Teva Investigational Site 21020
city: San Luís Potosí
country: Mexico
facility: Teva Investigational Site 21024
city: Chisinau
country: Moldova, Republic of
facility: Teva Investigational Site 70001
city: Chisinau
country: Moldova, Republic of
facility: Teva Investigational Site 70002
city: Chisinau
country: Moldova, Republic of
facility: Teva Investigational Site 70003
city: Chisinau
country: Moldova, Republic of
facility: Teva Investigational Site 70004
city: Podgorica
country: Montenegro
facility: Teva Investigational Site 66001
city: Bialystok
country: Poland
facility: Teva Investigational Site 53033
city: Czestochowa
country: Poland
facility: Teva Investigational Site 53020
city: Gdansk
country: Poland
facility: Teva Investigational Site 53023
city: Gdansk
country: Poland
facility: Teva Investigational Site 53024
city: Grodzisk Mazowiecki
country: Poland
facility: Teva Investigational Site 53031
city: Grodzisk Mazowiecki
country: Poland
facility: Teva Investigational Site 53032
city: Katowice
country: Poland
facility: Teva Investigational Site 53021
city: Kielce
country: Poland
facility: Teva Investigational Site 53019
city: Konstancin-Jeziorna
country: Poland
facility: Teva Investigational Site 53028
city: Koscierzyna
country: Poland
facility: Teva Investigational Site 53037
city: Lodz
country: Poland
facility: Teva Investigational Site 53018
city: Lublin
country: Poland
facility: Teva Investigational Site 53027
city: Olsztyn
country: Poland
facility: Teva Investigational Site 53036
city: Poznan / Plewiska
country: Poland
facility: Teva Investigational Site 53030
city: Poznan
country: Poland
facility: Teva Investigational Site 53034
city: Szczecin
country: Poland
facility: Teva Investigational Site 53025
city: Szczecin
country: Poland
facility: Teva Investigational Site 53026
city: Warsaw
country: Poland
facility: Teva Investigational Site 53022
city: Warszawa
country: Poland
facility: Teva Investigational Site 53029
city: Bucuresti
country: Romania
facility: Teva Investigational Site 52010
city: Bucuresti
country: Romania
facility: Teva Investigational Site 52012
city: Cluj-Napoca
country: Romania
facility: Teva Investigational Site 52015
city: Cluj-Napoca
country: Romania
facility: Teva Investigational Site 52016
city: Constanta
country: Romania
facility: Teva Investigational Site 52017
city: Constanta
country: Romania
facility: Teva Investigational Site 52018
city: Iasi
country: Romania
facility: Teva Investigational Site 52014
city: Oradea
country: Romania
facility: Teva Investigational Site 52021
city: Piatra-Neamt
country: Romania
facility: Teva Investigational Site 52011
city: Sibiu
country: Romania
facility: Teva Investigational Site 52013
city: Targu-Mures
country: Romania
facility: Teva Investigational Site 52020
city: Timisoara
country: Romania
facility: Teva Investigational Site 52019
city: Barnaul
country: Russian Federation
facility: Teva Investigational Site 50023
city: Chelyabinsk
country: Russian Federation
facility: Teva Investigational Site 50021
city: Kazan
country: Russian Federation
facility: Teva Investigational Site 50025
city: Krasnodar
country: Russian Federation
facility: Teva Investigational Site 50039
city: Moscow
country: Russian Federation
facility: Teva Investigational Site 50022
city: Moscow
country: Russian Federation
facility: Teva Investigational Site 50034
city: Moscow
country: Russian Federation
facility: Teva Investigational Site 50035
city: Moscow
country: Russian Federation
facility: Teva Investigational Site 50036
city: Nizhny Novgorod
country: Russian Federation
facility: Teva Investigational Site 50020
city: Nizhny Novgorod
country: Russian Federation
facility: Teva Investigational Site 50024
city: Nizhny Novgorod
country: Russian Federation
facility: Teva Investigational Site 50123
city: Novosibirsk
country: Russian Federation
facility: Teva Investigational Site 50027
city: Perm
country: Russian Federation
facility: Teva Investigational Site 50019
city: Rostov-on-Don
country: Russian Federation
facility: Teva Investigational Site 50038
city: Saint Petersburg
country: Russian Federation
facility: Teva Investigational Site 50032
city: Samara
country: Russian Federation
facility: Teva Investigational Site 50030
city: Saratov
country: Russian Federation
facility: Teva Investigational Site 50037
city: Smolensk
country: Russian Federation
facility: Teva Investigational Site 50028
city: St. Petersburg
country: Russian Federation
facility: Teva Investigational Site 50029
city: Tyumen
country: Russian Federation
facility: Teva Investigational Site 50031
city: Ufa
country: Russian Federation
facility: Teva Investigational Site 50026
city: Volgograd
country: Russian Federation
facility: Teva Investigational Site 50040
city: Yaroslavl
country: Russian Federation
facility: Teva Investigational Site 50033
city: Belgrade
country: Serbia
facility: Teva Investigational Site 61002
city: Belgrade
country: Serbia
facility: Teva Investigational Site 61005
city: Kragujevac
country: Serbia
facility: Teva Investigational Site 61001
city: Nis
country: Serbia
facility: Teva Investigational Site 61003
city: Chernihiv
country: Ukraine
facility: Teva Investigational Site 58022
city: Donetsk
country: Ukraine
facility: Teva Investigational Site 58030
city: Ivano-Frankivsk
country: Ukraine
facility: Teva Investigational Site 58020
city: Kharkiv
country: Ukraine
facility: Teva Investigational Site 58028
city: Kyiv
country: Ukraine
facility: Teva Investigational Site 58023
city: Kyiv
country: Ukraine
facility: Teva Investigational Site 58025
city: Lviv
country: Ukraine
facility: Teva Investigational Site 58018
city: Odessa
country: Ukraine
facility: Teva Investigational Site 58021
city: Poltava
country: Ukraine
facility: Teva Investigational Site 58029
city: Simferopol, AR Crimea
country: Ukraine
facility: Teva Investigational Site 58032
city: Uzhgorod
country: Ukraine
facility: Teva Investigational Site 58031
city: Vinnytsya
country: Ukraine
facility: Teva Investigational Site 58027
city: Zaporizhzhya
country: Ukraine
facility: Teva Investigational Site 58019
city: Zaporizhzhya
country: Ukraine
facility: Teva Investigational Site 58024
Study officials:
affiliation: Department of Neurology, Russian State Medical University
name: Alexey Boyko, MD
role: PRINCIPAL_INVESTIGATOR
References: