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Phase 2 trial of a DNA vaccine encoding myelin basic protein for multiple sclerosis
Journal
Annals of neurology
Volume
63
Number
5
Pages / Article-Number
611-20
Abstract
Objective: To evaluate the efficacy and safety of BHT-3009 in relapsing-remitting multiple sclerosis (MS) and to confirm that BHT-3009 causes immune tolerance.Methods: BHT-3009 is a tolerizing DNA vaccine for MS, encoding full-length human myelin basic protein. Relapsing-remitting MS patients were randomized 1:1:1 into three groups: placebo, 0.5mg BHT-3009, or 1.5mg BHT-3009, given intramuscularly at weeks 0, 2, 4, and every 4 weeks thereafter until week 44. The primary end point was the 4-week rate of occurrence of new gadolinium-enhancing lesions on brain magnetic resonance images from weeks 28 to 48. Protein microarrays were used to measure levels of anti-myelin autoantibodies.Results: Compared with placebo, in the 267 patient analysis population the median 4-week rate of new enhancing lesions during weeks 28 to 48 was 50% lower with 0.5mg BHT-3009 (p = 0.07) and during weeks 8 to 48 was 61% lower with 0.5mg BHT-3009 (P = 0.05). The mean volume of enhancing lesions at week 48 was 51% lower on 0.5mg BHT-3009 compared with placebo (p = 0.02). No significant improvement in magnetic resonance imaging lesion parameters was observed with 1.5mg BHT-3009. Dramatic reductions in 23 myelin-specific autoantibodies in the 0.5mg BHT-3009 arm were observed, but not with placebo or 1.5mg BHT-3009.Conclusions: In relapsing-remitting MS patients, treatment with the lower dose (0.5mg) of BHT-3009 for 44 weeks nearly attained the primary end point for reduction of the rate of new enhancing magnetic resonance imaging lesions (p = 0.07) and achieved several secondary end points including a reduction of the rate of enhancing magnetic resonance imaging lesions from weeks 8 to 48 (p = 0.05). Immunological data in a preselected subgroup of patients also indicated that treatment with 0.5mg induced antigen-specific immune tolerance. The greater dose was ineffective.
