Clinical trial NCT01874145: Safety and Tolerability of Glatiramer Acetate
Official title: An Open-Label, Randomized, Multi-Center, Parallel-Arm Study to Assess the Safety and Tolerability of Glatiramer Acetate 40 mg/mL Three Times a Week Compared to 20 mg/mL Daily Subcutaneous Injections in Subjects With Relapsing-Remitting Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Relapsing-Remitting Multiple Sclerosis
Keywords: Multiple Sclerosis
Relapsing-Remitting Multiple Sclerosis
Glatiramer Acetate
Glatiramer
Lead sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
Sponsor class: INDUSTRY
First posted: 2013-06-10
Enrollment: 209
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is an open-label, randomized, multi-center, parallel-arm study to assess the safety and tolerability of a daily dose of Glatiramer Acetate (GA) 40 mg/mL three times a week (TIW) administered subcutaneously (SC) as compared to GA 20 mg/mL every day (QD) administered SC.

Detailed description: The study will comprise of a Core study and an Extension phase. During the Core study, subjects will be evaluated at study sites for 5 scheduled visits at Months: -1 (Screening), 0 (Baseline), 1, 2, and 4 (Termination/Early Termination). Subjects who complete all scheduled visits will have final procedures and assessments performed at the final visit (Month 4, Termination visit). Subjects who withdraw from the study before completing the 4 months evaluation period will have Early Termination (ET) procedures and assessments performed at their final visit.

During the Extension phase, all subjects will be offered to continue treatment with GA 40 mg/mL TIW. Subjects will be evaluated every 4 months until this dose strength is commercially available for the treatment of Relapsing-Remitting Multiple Sclerosis (RRMS) patients or until the development of this GA dose regimen is stopped by the Sponsor, the last visit of this phase will be called Termination/ET-Extension visit.

Eligibility criteria: Inclusion Criteria:

1. Men or women at least 18 years of age or older
2. Subjects must have a confirmed and documented RRMS diagnosis as defined by the Revised McDonald criteria, with relapse onset disease or a relapsing-remitting disease course
3. Subjects must be ambulatory with a Kurtzke Expanded Disability Status Scale (EDSS) score of 0-5.5 in both the Screening and Baseline visits.
4. Subjects must be in a stable neurological condition, relapse-free and free of any corticosteroid treatment \[intravenous (IV), intramuscular (IM) and/or per os (PO)\] or adrenocorticotrophic hormone (ACTH), 60 days prior to randomization.
5. Subjects must be treated with Glatiramer Acetate (GA) 20mg/mL QD SC injection for a minimum of 6 months prior to screening.
6. Women of child-bearing potential must practice an acceptable method of birth control \[acceptable methods of birth control in this study include: surgical sterilization, intrauterine devices, oral contraceptives, contraceptive patch, long-acting injectable contraceptive, partner's vasectomy or a double-barrier method (condom or diaphragm with spermicide)\].
7. Subjects must be able to sign and date a written informed consent prior to entering the study.
8. Subjects must be willing and able to comply with the protocol requirements for the duration of the study

Exclusion Criteria:

1. Subject has any contraindication to Glatiramer Acetate therapy
2. Subjects with progressive forms of multiple sclerosis (MS).
3. Subjects with Neuromyelitis Optica (NMO).
4. Use of experimental or investigational drugs, and/or participation in drug clinical studies within the 6 months prior to screening.
5. Concomitant use of other disease modifying drug for MS ((Fingolimod (Gilenya®), dimethyl fumarate (Tecfidera®), Teriflunomide (Aubagio®) or intravenous immunoglobulin (IVIG)) within 6 months prior to screening
6. Previous use of mitoxantrone, cladribine, alemtuzumab, rituximab, natalizumab.
7. Chronic (more than 30 consecutive days) systemic (IV, PO or IM) corticosteroid treatment within 6 months prior to screening visit.
8. Previous total body irradiation or total lymphoid irradiation.
9. Previous stem-cell treatment, autologous bone marrow transplantation or allogenic bone marrow transplantation.
10. Pregnancy or breastfeeding.
11. 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 and abnormal laboratory tests. 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.
12. Subjects who underwent endovascular treatment for Chronic Cerebrospinal Venous Insufficiency (CCSVI).
13. Employees of the clinical study site or any other individuals involved with the conduct of the study, or immediate family members of such individuals -

Primary outcomes:
measure: Adjusted Mean Estimates for Injection-Related Adverse Event Rate Per Year in the Core Period
timeFrame: Day 1 to Month 4
measure: Injection-Related Adverse Event Rate Per Year in the Extension Period
timeFrame: Month 5 up to Month 10
measure: Injection-Related Adverse Events in the Extension Period
timeFrame: Month 5 up to Month 10
Secondary outcomes:
measure: Adjusted Mean Estimates for Injection Site Reaction Event Rate Per Year in the Core Period
timeFrame: Day 1 to Month 4
measure: Change From Baseline to Month 4 in in the Adjusted Mean Participant-Reported Impact on Physical Wellbeing Using Multiple Sclerosis Impact Scale (MSIS-29 PRO) in the Core Period
timeFrame: Month 0 (baseline), Months 1, 2, 4 (or early termination visit)
measure: Change From Baseline to Month 4 in in the Adjusted Mean Participant-Reported Impact on Psychological Wellbeing Using Multiple Sclerosis Impact Scale (MSIS-29 PRO) in the Core Period
timeFrame: Month 0 (baseline), Months 1, 2 4 (or early termination visit)
measure: Change From Baseline to Month 4 in in the Adjusted Mean Participant-Reported Treatment Satisfaction Questionnaire for Medication (TSQM-9) Convenience Score in the Core Period
timeFrame: Month 0 (baseline), Months 1, 2 4 (or early termination visit)
measure: Change From Baseline to Month 4 in in the Adjusted Mean Participant-Reported Treatment Satisfaction Questionnaire for Medication (TSQM-9) Satisfaction Score in the Core Period
timeFrame: Month 0 (baseline), Months 1, 2 4 (or early termination visit)
measure: Injection Site Reaction Event Rate Per Year in the Extension Period
timeFrame: Month 5 up to Month 10
measure: Injection Site Reaction Events in the Extension Period
timeFrame: Month 5 up to Month 10
measure: Change From Start of Extension Period (Month 4) to Month 8 (and to Endpoint Visit) in the Participant-Reported Impact on Physical Wellbeing Using Multiple Sclerosis Impact Scale (MSIS-29 PRO)
timeFrame: Month 4 (baseline for extension period), Month 8, endpoint visit
measure: Change From Start of Extension Period (Month 4) to Month 8 (and to Endpoint Visit) in the Participant-Reported Impact on Psychological Wellbeing Using Multiple Sclerosis Impact Scale (MSIS-29 PRO)
timeFrame: Month 4 (baseline for extension period), Month 8, endpoint visit
measure: Change From Start of Extension Period to Month 8 (and to Endpoint Visit) in in the Participant-Reported Treatment Satisfaction Questionnaire for Medication (TSQM-9) Convenience Score
timeFrame: Month 4 (baseline for extension period), Month 8, endpoint visit
measure: Change From Start of Extension Period to Month 8 (and to Endpoint Visit) in in the Participant-Reported Treatment Satisfaction Questionnaire for Medication (TSQM-9) Satisfaction Score
timeFrame: Month 4 (baseline for extension period), Month 8, endpoint visit
Other outcomes:
measure: Percentage of Participants With Adverse Events Other Than Injection Related Reactions During the Core Period and the Extension Period
timeFrame: Day 1 to Month 4 (core period); Month 5 to 10 (extension period)
Locations:
city: Cullman
country: United States
facility: Teva Investigational Site 10706
state: Alabama
city: Gilbert
country: United States
facility: Teva Investigational Site 10719
state: Arizona
city: Phoenix
country: United States
facility: Teva Investigational Site 10720
state: Arizona
city: Fresno
country: United States
facility: Teva Investigational Site 10727
state: California
city: Long Beach
country: United States
facility: Teva Investigational Site 10731
state: California
city: Newport Beach
country: United States
facility: Teva Investigational Site 10735
state: California
city: Oceanside
country: United States
facility: Teva Investigational Site 10712
state: California
city: Centennial
country: United States
facility: Teva Investigational Site 10708
state: Colorado
city: Maitland
country: United States
facility: Teva Investigational Site 10715
state: Florida
city: Pompano Beach
country: United States
facility: Teva Investigational Site 10718
state: Florida
city: St. Petersburg
country: United States
facility: Teva Investigational Site 10709
state: Florida
city: Tampa
country: United States
facility: Teva Investigational Site 10707
state: Florida
city: Tampa
country: United States
facility: Teva Investigational Site 10711
state: Florida
city: Northbrook
country: United States
facility: Teva Investigational Site 10710
state: Illinois
city: Indianapolis
country: United States
facility: Teva Investigational Site 10734
state: Indiana
city: Baltimore
country: United States
facility: Teva Investigational Site 10732
state: Maryland
city: Great Falls
country: United States
facility: Teva Investigational Site 10726
state: Montana
city: Henderson
country: United States
facility: Teva Investigational Site 10702
state: Nevada
city: Patchogue
country: United States
facility: Teva Investigational Site 10717
state: New York
city: Plainview
country: United States
facility: Teva Investigational Site 10723
state: New York
city: Charlotte
country: United States
facility: Teva Investigational Site 10716
state: North Carolina
city: Raleigh
country: United States
facility: Teva Investigational Site 10724
state: North Carolina
city: Winston-Salem
country: United States
facility: Teva Investigational Site 10721
state: North Carolina
city: Bellevue
country: United States
facility: Teva Investigational Site 10733
state: Ohio
city: Columbus
country: United States
facility: Teva Investigational Site 10703
state: Ohio
city: Dayton
country: United States
facility: Teva Investigational Site 10714
state: Ohio
city: Uniontown
country: United States
facility: Teva Investigational Site 10704
state: Ohio
city: East Providence
country: United States
facility: Teva Investigational Site 10725
state: Rhode Island
city: Cordova
country: United States
facility: Teva Investigational Site 10736
state: Tennessee
city: Franklin
country: United States
facility: Teva Investigational Site 10701
state: Tennessee
city: Nashville
country: United States
facility: Teva Investigational Site 10728
state: Tennessee
city: Mansfield
country: United States
facility: Teva Investigational Site 10729
state: Texas
city: Round Rock
country: United States
facility: Teva Investigational Site 10722
state: Texas
city: Salt Lake City
country: United States
facility: Teva Investigational Site 10699
state: Utah
city: Roanoke
country: United States
facility: Teva Investigational Site 10700
state: Virginia
Study officials:
References:
citation: Wolinsky JS, Borresen TE, Dietrich DW, Wynn D, Sidi Y, Steinerman JR, Knappertz V, Kolodny S; GLACIER Study Group. GLACIER: An open-label, randomized, multicenter study to assess the safety and tolerability of glatiramer acetate 40 mg three-times weekly versus 20 mg daily in patients with relapsing-remitting multiple sclerosis. Mult Scler Relat Disord. 2015 Jul;4(4):370-6. doi: 10.1016/j.msard.2015.06.005. Epub 2015 Jun 14.