Phase 2 trial of a DNA vaccine encoding myelin basic protein for multiple sclerosis

Hideki Garren, William H. Robinson, Eva Krasulová, Eva Havrdová, Congor Nadj, Krzysztof Selmaj, Jacek Losy, Ilinka Nadj, Ernst Wilhelm Radue, Brian A. Kidd, Jill Gianettoni, Karen Tersini, Paul J. Utz, Frank Valone, Lawrence Steinman, Ivan Milanov, Dimitar Georgiev, Penko Shotekov, Paraskeva Stamenova, Slobodan VojinovicPetr Kanovsky, David Dolezil, Edvard Ehler, Otakar Keller, Pavel Stourac, Juha Pekka Erälinna, Keijo Koivisto, Jussi Valpas, Yuriy Golovchenko, Larysa Sokolova, Anatoliy Grinchuk, Sergiy Moskovko, Hubert Kwiecinski, Andrzej Wajgt, Andrzej Tutaj, Ryszard Podemski, Sanda Nica, Rodica Balasa, Mihaela Adriana Simu, Igor Stolyarov, Miroslav Odinak, Alexander Skoromets, Eugeny Gusev, Igor Zavalishin, Anna N. Belova, Leonid Zaslavskiy, Peter Turcani, Lubica Prochazkova, Juraj Vyletelka, Egon Kurca, Jarmila Szilasiova, Christopher Hawkes, Basil Sharrack, Lloyd Kasper

Research output: Contribution to journalArticlepeer-review

164 Scopus citations

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.

Original languageEnglish
Pages (from-to)611-620
Number of pages10
JournalAnnals of Neurology
Volume63
Issue number5
DOIs
StatePublished - May 2008
Externally publishedYes

Fingerprint

Dive into the research topics of 'Phase 2 trial of a DNA vaccine encoding myelin basic protein for multiple sclerosis'. Together they form a unique fingerprint.

Cite this