This is a study evaluating the effect on brain volume of daily glatiramer acetate (GA) and add-on pulse steroids.
One interim analysis was planned for possible early termination due to proven efficacy when 75% of the preplanned 500 (approx. 375 patients) recruited patients completed the entire study duration or early discontinued. In addition to the stopping rule already given for proven efficacy, the sponsor was also interested in examining the data for futility (i.e., absence of the desired treatment effect) with the view to terminating the trial if an "insufficient" effect of the treatment is seen. The reasons why the need for futility arose were: 1. Recruitment difficulties 2. Increasing dropout rate 3. Budgetary constraints The primary efficacy measure is defined as the percent change from baseline to termination (Month 36 or Early Termination) in normalized brain volume (Brain Atrophy) measured according to the SIENA (Structural Imaging Evaluation using Normalization of Atrophy) method. However, since not many patients had completed the entire study at the time of futility analysis, it was the sponsor's decision that the futility analysis be performed on patients with MRI scans at months 24 or 36 or at early termination visits - the latest available. Based on the recalculation of study power (probability is unconditioned on the interim result and provide the real power of the study if designed anew), conditional power (based on the interim results) and risk assessment of a false negative, the Data Monitoring Committee agreed that the study should be terminated early.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
414
20mg glatiramer acetate (GA) administered by daily subcutaneous injections
Placebo for prednisone given daily
Prednisone 1250 mg taken daily
Percent Change From Baseline to Termination in Normalized Brain Volume Measured According to the SIENA (Structural Imaging Evaluation Using Normalization of Atrophy) Method
Results represent the database as of January 29, 2009. Brain volume was measured at baseline and at months 24, 36 and at early termination visits by magnetic resonance imaging (MRI). Brain atrophy was measured by comparing the change in brain volume from baseline to the latest scan at the three during study timeframes. SIENA is a fully automated method of analyzing longitudinal brain change. Adjusted (least square) mean values are presented.
Time frame: Day 0, latest scan at month 24, 36 or early termination visit
Cumulative Number of Enhancing Lesions at Months 12, 24 and 36
Results represent the database as of January 29, 2009. Enhancing lesions are lesions that show inflammation on an MRI and are assumed to be new lesions. The sum of enhancing lesions observed in MRIs taken at months 12, 24 and 36 are offered.
Time frame: Months 12, 24, and 36
Change From Baseline to Month 36 or Early Termination Visit in Volume of T2-Lesions
Results represent the database as of January 29, 2009. The difference in T2 brain lesion volume as observed in MRIs from baseline to Month 36 or the early termination visit. T2 lesions are hyperintense lesions meaning that they appear as bright spots on the MRI image. These tend to show the total number of lesions and disease burden.
Time frame: Day 0, Month 36 or the early termination visit
Change From Baseline to Month 36 or Early Termination Visit in Volume of Hypointense Lesions
Results represent the database as of January 29, 2009. The difference in hypointense brain lesion volume as observed in MRIs from baseline to Month 36 or the early termination visit. Hypointense lesions display as dark areas on the MRI image, and represent areas of permanent axonal damage.
Time frame: Day 0, Month 36 or early termination visit
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