Relapsing-Remitting Multiple Sclerosis
Conditions
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.
Interventions
DRUGGlatiramer 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.
DRUGPlacebo
Matching placebo injection; 20 mg mannitol dissolved in 0.5 mL water for subcutaneous injection in a PFS is administered daily.
Sponsors
Teva Branded Pharmaceutical Products R&D, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Annualized Relapse Rate During the Placebo Controlled Period | Day 1 up to Month 12 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Cumulative Number of New or Enlarging T2 Lesions Measured at Months 6 and 12 (End of Placebo Controlled Period) | Day 1 up to Month 12 | Inflammatory disease activity was assessed by magnetic resonance imaging (MRI) measurement of the number of new or newly enlarged T2 lesions. |
| The Cumulative Number of Gadolinium-enhancing Lesions on T1-weighted Images Measured at Months 6 and 12 (End of Placebo Controlled Period) | Day 1 up to Month 12 | Inflammatory disease activity was assessed by magnetic resonance imaging (MRI) measurement of the number of gadolinium-enhanced T1 lesions. |
| Percent Change From Baseline to Month 12 (End of Placebo Controlled Period) in Brain Volume | Day 1 up to Month 12 | Brain atrophy was defined by the percent brain volume change from baseline to Month 12 |
Countries
Albania, Belarus, Bosnia and Herzegovina, Bulgaria, Croatia, Estonia, Georgia, Greece, Latvia, Mexico, Moldova, Montenegro, North Macedonia, Poland, Romania, Russia, Serbia, Ukraine, United States
Participant flow
Pre-assignment details
Two hundred seventy-four patients were screened and 178 randomized into the study in a 1:2 treatment arm ratio.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo solution in prefilled syringe for subcutaneous injection once daily. | 59 |
| GA 20 mg/0.5 ml Glatiramer acetate (GA) 20 mg/0.5 ml solution in prefilled syringe for subcutaneous injection once daily. | 119 |
| Total | 178 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Study terminated by sponsor | 59 | 118 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo | Total | GA 20 mg/0.5 ml |
|---|---|---|---|
| Age, Continuous AgeContinuous | 37.7 years STANDARD_DEVIATION 9.13 | 38.5 years STANDARD_DEVIATION 8.62 | 38.9 years STANDARD_DEVIATION 8.36 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 59 Participants | 178 Participants | 119 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 58 Participants | 176 Participants | 118 Participants |
| Region of Enrollment Belarus | 4 participants | 8 participants | 4 participants |
| Region of Enrollment Bosnia and Herzegovina | 6 participants | 17 participants | 11 participants |
| Region of Enrollment Bulgaria | 7 participants | 29 participants | 22 participants |
| Region of Enrollment Croatia | 7 participants | 25 participants | 18 participants |
| Region of Enrollment Estonia | 0 participants | 1 participants | 1 participants |
| Region of Enrollment Georgia | 6 participants | 14 participants | 8 participants |
| Region of Enrollment Poland | 19 participants | 54 participants | 35 participants |
| Region of Enrollment Romania | 9 participants | 28 participants | 19 participants |
| Region of Enrollment USA | 1 participants | 2 participants | 1 participants |
| Sex: Female, Male Female | 45 Participants | 132 Participants | 87 Participants |
| Sex: Female, Male Male | 14 Participants | 46 Participants | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 59 | 22 / 119 |
| serious Total, serious adverse events | 0 / 59 | 0 / 119 |
Outcome results
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.
Time frame: Day 1 up to Month 12
Population: Intent to treat population was planned. However analysis was not performed due to early termination of the study.
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
Time frame: Day 1 up to Month 12
Population: Intent to treat population was planned. However analysis was not performed due to early termination of the study.
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.
Time frame: Day 1 up to Month 12
Population: Intent to treat population was planned. However analysis was not performed due to early termination of the study.
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.
Time frame: Day 1 up to Month 12
Population: Intent to treat population was planned. However analysis was not performed due to early termination of the study.