A phase I trial of solubilized DR2:MBP84-102 (AG284) in multiple sclerosis
| Autor: | Nancy J. Fischbein, Lawrence Jacobs, Elliot M. Frohman, Sarah J. Nelson, M. Shulman, Donald E. Goodkin, T. Stewart, S. Mocci, J. Holcenberg, M. Lee, Patricia K. Coyle, P. B. Andersson, Emmanuelle Waubant, J. Winkelhake |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Adult
Male medicine.medical_specialty Encephalomyelitis T-Lymphocytes Dose-Response Relationship Immunologic Placebo Gastroenterology Myelin Interferon-gamma Double-Blind Method HLA Antigens Internal medicine medicine Humans HLA-DR2 Antigen Adverse effect Autoantibodies Expanded Disability Status Scale Vaccines Conjugate business.industry Multiple sclerosis Brain Myelin Basic Protein Middle Aged Multiple Sclerosis Chronic Progressive medicine.disease Magnetic Resonance Imaging Peptide Fragments Clinical trial Myelin-Associated Glycoprotein medicine.anatomical_structure Treatment Outcome Tolerability Immunology Female Myelin-Oligodendrocyte Glycoprotein Neurology (clinical) Immunotherapy business Myelin Proteins |
| Zdroj: | Neurology. 54(7) |
| ISSN: | 0028-3878 |
| Popis: | Objective: To assess the safety, tolerability, and biologic and clinical activity of a solubilized complex comprised of human leukocyte antigen—DR2 with myelin basic protein84-102 (AG284)in patients with secondary progressive MS. Background: Soluble species-specific major histocompatibility complex myelin basic protein91-103 complexes ameliorate disease in a dose-dependent manner when administered to SJL/J mice with chronic relapsing experimental allergic encephalomyelitis. Preincubation with AG284 reduces the proliferative response of a DR2-restricted, myelin basic protein84-102–reactive T cell clone, derived from a MS patient, to myelin basic protein84-102 in the presence of autologous antigen-presenting cells. Methods: Thirty-three patients with secondary progressive MS were randomly assigned to receive three alternate day IV doses of AG284 or placebo in a double-masked dose escalation study. The primary outcome was safety and tolerability. Secondary outcomes included a comparison of pre- and post-treatment gadolinium-enhanced brain MRI activity, Kurtzke Expanded Disability Status Scale, and Nine Hole Peg Test scores. Results: The frequency of adverse events was similar in the AG284 and placebo recipients. No significant treatment effect was detected by Expanded Disability Status Scale, Nine Hole Peg Test, or number of new gadolinium-enhancing MRI lesions. Conclusions: AG284 as administered during this study was safe and well tolerated. Further studies are warranted to determine the biologic activity and clinical efficacy of this potential treatment for MS. |
| Databáze: | OpenAIRE |
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