Phase 2 trial of a DNA vaccine encoding myelin basic protein for multiple sclerosis
| العنوان: | Phase 2 trial of a DNA vaccine encoding myelin basic protein for multiple sclerosis |
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| المؤلفون: | 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, Lloyd, Kasper |
| المصدر: | Annals of Neurology. 63:611-620 |
| بيانات النشر: | Wiley, 2008. |
| سنة النشر: | 2008 |
| مصطلحات موضوعية: | Adult, Male, medicine.medical_specialty, Pathology, Multiple Sclerosis, Adolescent, Maximum Tolerated Dose, Population, Placebo, Gastroenterology, Central nervous system disease, Lesion, Internal medicine, Vaccines, DNA, medicine, Clinical endpoint, Humans, education, education.field_of_study, biology, medicine.diagnostic_test, business.industry, Multiple sclerosis, Myelin Basic Protein, Magnetic resonance imaging, Middle Aged, medicine.disease, Myelin basic protein, Treatment Outcome, Neurology, biology.protein, Female, Neurology (clinical), medicine.symptom, business |
| الوصف: | 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. Relapsingremitting 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. Ann Neurol 2008;63:611‐620 |
| تدمد: | 1531-8249 0364-5134 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e9a4760a292e1452e75b1f84eaae1075 https://doi.org/10.1002/ana.21370 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....e9a4760a292e1452e75b1f84eaae1075 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15318249 03645134 |
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