[P02.137] Autologous Attenuated T Cell Vaccine (Tovaxin) Dose Escalation in Multiple Sclerosis Relapse-Remitting and Secondary Progressive Patients Nonresponsive to Approved Immunomodulatory Therapies

Brian Loftus, Bellaire, TX, Brian Newsom, Mitzi Montgomery, Jay, OK, Von Gynz-Rekowski Kathrin, Mary Riser, Shannon Inman, Pablo Garces, Donna Rill, Jim Williams, The Woodlands, TX

OBJECTIVE: To assess the safety and effectiveness of T cell vaccine in multiple sclerosis patients non-responsive to approved immunomodulatory therapies. BACKGROUND: Autologous T cell vaccination uses attenuated myelin reactive T cells (MRTC) to induce anti-idiotypic and anti-ergotypic immune regulatory responses which clonally deplete and regulate circulating MRTC. An open-label dose escalation study was conducted to determine a safe and effective dose for phase 2 clinical trials. DESIGN/METHODS: Participants were 56% RRMS, 44% SPMS, four (25%) male, 12 (75%) female, 15 (94%) Caucasian, one (6%) Hispanic, and average age 46 years (24-62) and median 48. Six myelin peptides, two each from MBP, PLP and MOG, were used to select MRTC to produce T cell vaccine for each subject. The dose range in millions of T cells was 6-9, 30-45 and 60-90 irradiated MRTC. Subcutaneous injections were given at Weeks 0, 4, 12 and 20. Assessments for exacerbations (Annualized Relapse Rate), EDSS and MRTC were conducted for 52 weeks. RESULTS: Adverse events were mild or moderate in intensity with mild injection site reactions occurring with increasing dosage. Reduction of MRTC in peripheral blood following vaccinations was shown for all doses. The 30-45 million dose was the most effective. At Weeks 5, 13, 21, 28 and 52, MRTC levels were reduced by 92.4%, 86.9%, 79.4%, 76.7% and 64.8%, respectively, without globally suppressing the immune system. The reduction in ARR compared to baseline (ARR past 1 and 2 years) for the M-ITT, evaluable and per protocol analyses were 63.5% (p = 0.0576), 59.8% (p = 0.0898) and 90.0% (p = 0.0039, Wilcoxon Signed Rank test), respectively. CONCLUSIONS/RELEVANCE: Statistically significant improvements from baseline were observed using the ARR and MRTC count effectiveness measurements. The mid-dose was selected for Phase 2 studies. Tovaxin is well-tolerated with only mild injection site reactions with increasing dosage but all resolved rapidly. Supported by: Opexa Therapeutics, Inc.
Category - MS and Related Diseases
SubCategory - Clinical Science

Tuesday, April 15, 2008 11:30 AM

Poster Sessions II: Multiple Sclerosis and Related Diseases: Therapeutics (11:30 AM-2:30 PM)

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