Relapsing Remitting Multiple Sclerosis
Conditions
Brief summary
Teva is developing a 40 mg/ml GA Injection, administered once daily under the skin, for the treatment of R-R MS. The study drug is a higher dose formulation of Copaxone® (20 mg/ml GA), a marketed medication, approved for the treatment of R-R MS. GA is an immunomodulating drug that has anti inflammatory and neuroprotective properties. The study treatment duration is 12 months.
Interventions
DRUGGlatiramer Acetate (GA) 40 mg
Glatiramer Acetate Injection 40 mg/ml Daily subcutaneous injection for 12 months
Glatiramer Acetate Injection 20 mg/ml Daily subcutaneous injection for 12 months
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
1. Diagnosis of confirmed and documented MS defined by the Revised McDonald criteria. 2. Subjects must be of the relapsing-remitting (R-R) type. 3. Subject has experienced prior to screening at least one documented relapse in 12 months or at least 2 documented relapses in the 24 months or one documented relapse between 12 - 24 months with at least 1 documented T1-Gd enhancing lesion in the MRI performed 12 months prior screening. 4. Disease duration for at least 6 months. 5. Ambulatory with converted Kurtzke EDSS score of 0 - 5. 6. Relapse free and stable neurological condition at least for 30 days prior screening. 7. Age - 18-55 (inclusive)
Exclusion criteria
1. Previous use of Copaxone (glatiramer acetate) 2. Treatment with corticosteroids within 30 days prior screening or between screening and baseline. 3. Chronic corticosteroids treatment - more than 30 consecutive days. 4. Subject with any clinically significant or unstable medical condition. 5. Subjects participating in any other clinical trial (within 12 weeks prior to screening and thereafter). 6. Known history of sensitivity to Gadolinium and inability to successfully undergo MRI scanning.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Rate of Confirmed Relapses During the Double-blind Phase (12 Months). | 12 months | A confirmed relapse is defined as the appearance of one or more new neurological abnormalities or the reappearance of one or more previously observed neurological abnormalities. This change in clinical state must last at least 48 hours and be immediately preceded by an improving neurological state of at least thirty (30) days from onset of previous relapse. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Number of New T2 Lesions at Month 12 as Compared to the Baseline Scan. | 12 months | The analysis of this endpoint was based on the outcome of a contrast derived from a baseline-adjusted Negative Binomial Regression including the number of T1 Gd-enhancing lesions at baseline, the volume of T2 lesions at baseline and (pooled) center as covariates. |
| The Cumulative Number of T1-Gd Enhancing Lesions at Months 3, 6, 9 and 12 (in the Frequent MRI Cohort-described Below). | 12 months | The Frequent MRI Cohort was a subset of subjects consisting of 234 subjects, for whom MRI scans were performed at months 0 (baseline), 1, 2, 3, 6, 9 and 12. Analysis of the endpoint was based on the outcome of a contrast derived from a baseline-adjusted Negative Binomial Regression with an offset variable employing the log of the porportion of the number of available post-baseline scans to adjust for missing MRI scans (if any) and including the number of T1 Gd-enhancing lesions at baseline and (pooled) center as covariates. |
Participant flow
Recruitment details
Study was conducted according to laws, regulations and administrative provisions related to implementation of Good Clinical Practice as applicable by legislation directives and Standard Operating Procedures. Subjects entered study after being informed and given time to contemplate consent. Enrollment began September 2006 and completed May 2007
Pre-assignment details
All subjects underwent evaluations including vital signs (blood pressure, pulse, and temperature,) adverse events, concomitant medications and neurological evaluation prior to study entry.
Participants by arm
| Arm | Count |
|---|---|
| Glatiramer Acetate 20 mg | 586 |
| Glatiramer Acetate 40 mg | 569 |
| Total | 1,155 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 28 | 51 |
| Overall Study | Death | 0 | 1 |
| Overall Study | Lost to Follow-up | 6 | 5 |
| Overall Study | Physician Decision | 3 | 6 |
| Overall Study | Pregnancy | 3 | 2 |
| Overall Study | Protocol Violation | 1 | 1 |
| Overall Study | Sponsor decision | 1 | 1 |
| Overall Study | Withdrawal by Subject | 10 | 12 |
Baseline characteristics
| Characteristic | Glatiramer Acetate 20 mg | Total | Glatiramer Acetate 40 mg |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 586 Participants | 1155 Participants | 569 Participants |
| Age Continuous | 36.3 years STANDARD_DEVIATION 9 | 36.3 years STANDARD_DEVIATION 9 | 36.3 years STANDARD_DEVIATION 9 |
| Region of Enrollment Argentina | 14 participants | 28 participants | 14 participants |
| Region of Enrollment Belgium | 0 participants | 1 participants | 1 participants |
| Region of Enrollment Canada | 15 participants | 28 participants | 13 participants |
| Region of Enrollment Czech Republic | 33 participants | 67 participants | 34 participants |
| Region of Enrollment Estonia | 11 participants | 23 participants | 12 participants |
| Region of Enrollment Finland | 9 participants | 16 participants | 7 participants |
| Region of Enrollment France | 10 participants | 21 participants | 11 participants |
| Region of Enrollment Germany | 50 participants | 98 participants | 48 participants |
| Region of Enrollment Hungary | 27 participants | 54 participants | 27 participants |
| Region of Enrollment Israel | 14 participants | 28 participants | 14 participants |
| Region of Enrollment Italy | 47 participants | 90 participants | 43 participants |
| Region of Enrollment Latvia | 14 participants | 28 participants | 14 participants |
| Region of Enrollment Lithuania | 14 participants | 28 participants | 14 participants |
| Region of Enrollment Netherlands | 7 participants | 13 participants | 6 participants |
| Region of Enrollment Poland | 36 participants | 71 participants | 35 participants |
| Region of Enrollment Romania | 29 participants | 57 participants | 28 participants |
| Region of Enrollment Russian Federation | 87 participants | 175 participants | 88 participants |
| Region of Enrollment Spain | 23 participants | 45 participants | 22 participants |
| Region of Enrollment United Kingdom | 11 participants | 21 participants | 10 participants |
| Region of Enrollment United States | 135 participants | 263 participants | 128 participants |
| Sex: Female, Male Female | 421 Participants | 828 Participants | 407 Participants |
| Sex: Female, Male Male | 165 Participants | 327 Participants | 162 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 499 / 586 | 490 / 569 |
| serious Total, serious adverse events | 25 / 586 | 24 / 569 |
Outcome results
Primary
The Rate of Confirmed Relapses During the Double-blind Phase (12 Months).
A confirmed relapse is defined as the appearance of one or more new neurological abnormalities or the reappearance of one or more previously observed neurological abnormalities. This change in clinical state must last at least 48 hours and be immediately preceded by an improving neurological state of at least thirty (30) days from onset of previous relapse.
Time frame: 12 months
Population: ITT
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glatiramer Acetate 20 mg | The Rate of Confirmed Relapses During the Double-blind Phase (12 Months). | 0.28 Number of relapses per patient | Standard Deviation 0.58 |
| Glatiramer Acetate 40 mg | The Rate of Confirmed Relapses During the Double-blind Phase (12 Months). | 0.27 Number of relapses per patient | Standard Deviation 0.54 |
p-value: 0.485995% CI: [0.8799, 1.309]Regression, Poisson
Secondary
The Cumulative Number of T1-Gd Enhancing Lesions at Months 3, 6, 9 and 12 (in the Frequent MRI Cohort-described Below).
The Frequent MRI Cohort was a subset of subjects consisting of 234 subjects, for whom MRI scans were performed at months 0 (baseline), 1, 2, 3, 6, 9 and 12. Analysis of the endpoint was based on the outcome of a contrast derived from a baseline-adjusted Negative Binomial Regression with an offset variable employing the log of the porportion of the number of available post-baseline scans to adjust for missing MRI scans (if any) and including the number of T1 Gd-enhancing lesions at baseline and (pooled) center as covariates.
Time frame: 12 months
Population: Frequent MRI cohort
| Arm | Measure | Value (LOG_MEAN) | Dispersion |
|---|---|---|---|
| Glatiramer Acetate 20 mg | The Cumulative Number of T1-Gd Enhancing Lesions at Months 3, 6, 9 and 12 (in the Frequent MRI Cohort-described Below). | 2.83 T1 Enhancing Lesions | Standard Deviation 6.58 |
| Glatiramer Acetate 40 mg | The Cumulative Number of T1-Gd Enhancing Lesions at Months 3, 6, 9 and 12 (in the Frequent MRI Cohort-described Below). | 3.49 T1 Enhancing Lesions | Standard Deviation 8.19 |
Secondary
The Number of New T2 Lesions at Month 12 as Compared to the Baseline Scan.
The analysis of this endpoint was based on the outcome of a contrast derived from a baseline-adjusted Negative Binomial Regression including the number of T1 Gd-enhancing lesions at baseline, the volume of T2 lesions at baseline and (pooled) center as covariates.
Time frame: 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glatiramer Acetate 20 mg | The Number of New T2 Lesions at Month 12 as Compared to the Baseline Scan. | 2.87 T2 Lesions | Standard Deviation 6.57 |
| Glatiramer Acetate 40 mg | The Number of New T2 Lesions at Month 12 as Compared to the Baseline Scan. | 2.72 T2 Lesions | Standard Deviation 8.36 |