Open AccessA randomized clinical trial of autologous T-cell therapy in multiple sclerosis: subset analysis and implications for trial design
Author(s) -
Edward Fox,
Daniel Wynn,
Stanley Cohan,
Donna Rill,
Dawn McGuire,
Clyde Markowitz
Publication year - 2011
Publication title -
multiple sclerosis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.729
H-Index - 131
eISSN - 1477-0970
pISSN - 1352-4585
DOI - 10.1177/1352458511428462
Subject(s) - medicine , multiple sclerosis , placebo , clinically isolated syndrome , immunotherapy , oncology , clinical trial , population , randomized controlled trial , immunology , pathology , cancer , alternative medicine , environmental health
Background: Tovaxin is an autologous T-cell immunotherapy under investigation for the treatment of MS. The product consists of in vitro expanded myelin-reactive T-cells manufactured against up to six immunodominant peptides derived from three myelin antigens. Methods: A Phase 2b placebo controlled study (TERMS) was conducted in 150 subjects to gather safety and efficacy data in relapsing-remitting MS and clinically isolated syndrome subjects. Results: Tovaxin had a favorable safety profile. Although no statistically significant clinical or radiological benefit of Tovaxin immunotherapy was identified in the modified intent-to-treat population, a prospective analysis of subjects with more active disease favored Tovaxin in terms of annualized relapse rate (ARR) and disability progression. An analysis also found a possible legacy effect of prior disease-modifying treatment (DMT) which may have contributed to a lowered ARR in the placebo group. DMT-naïve subjects treated with Tovaxin had a lower ARR compared to the placebo group, particularly in those with active baseline disease (ARR≥1, ARR>1). However, clinical benefit was not was accompanied by a treatment-dependent improvement in MRI measures. Conclusions: Previous DMT exposure may reduce effect size and study power. Limiting subject selection to DMT-treatment-naïve individuals may be a reasonable approach to phase 2 or proof-of-concept studies of limited duration.