A phase I trial of solubilized DR2

MBP84-102 (AG284) in multiple sclerosis

Donald E. Goodkin, M. Shulman, J. Winkelhake, E. Waubant, P. B. Andersson, T. Stewart, S. Nelson, N. Fischbein, P. K. Coyle, Elliot Frohman, L. Jacobs, J. Holcenberg, M. Lee, S. Mocci

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1414-1420
Number of pages7
JournalNeurology
Volume54
Issue number7
StatePublished - Apr 11 2000

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Multiple Sclerosis
Myelin Sheath
Gadolinium
Placebos
Safety
Autoimmune Experimental Encephalomyelitis
Autoantigens
Antigen-Presenting Cells
HLA Antigens
Major Histocompatibility Complex
Therapeutics
Clone Cells
myelin basic protein 84-102
T-Lymphocytes
Brain

Keywords

  • AG284
  • Anergy
  • Clinical trials
  • MS
  • Myelin

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Goodkin, D. E., Shulman, M., Winkelhake, J., Waubant, E., Andersson, P. B., Stewart, T., ... Mocci, S. (2000). A phase I trial of solubilized DR2: MBP84-102 (AG284) in multiple sclerosis. Neurology, 54(7), 1414-1420.

A phase I trial of solubilized DR2 : MBP84-102 (AG284) in multiple sclerosis. / Goodkin, Donald E.; Shulman, M.; Winkelhake, J.; Waubant, E.; Andersson, P. B.; Stewart, T.; Nelson, S.; Fischbein, N.; Coyle, P. K.; Frohman, Elliot; Jacobs, L.; Holcenberg, J.; Lee, M.; Mocci, S.

In: Neurology, Vol. 54, No. 7, 11.04.2000, p. 1414-1420.

Research output: Contribution to journalArticle

Goodkin, DE, Shulman, M, Winkelhake, J, Waubant, E, Andersson, PB, Stewart, T, Nelson, S, Fischbein, N, Coyle, PK, Frohman, E, Jacobs, L, Holcenberg, J, Lee, M & Mocci, S 2000, 'A phase I trial of solubilized DR2: MBP84-102 (AG284) in multiple sclerosis', Neurology, vol. 54, no. 7, pp. 1414-1420.
Goodkin DE, Shulman M, Winkelhake J, Waubant E, Andersson PB, Stewart T et al. A phase I trial of solubilized DR2: MBP84-102 (AG284) in multiple sclerosis. Neurology. 2000 Apr 11;54(7):1414-1420.
Goodkin, Donald E. ; Shulman, M. ; Winkelhake, J. ; Waubant, E. ; Andersson, P. B. ; Stewart, T. ; Nelson, S. ; Fischbein, N. ; Coyle, P. K. ; Frohman, Elliot ; Jacobs, L. ; Holcenberg, J. ; Lee, M. ; Mocci, S. / A phase I trial of solubilized DR2 : MBP84-102 (AG284) in multiple sclerosis. In: Neurology. 2000 ; Vol. 54, No. 7. pp. 1414-1420.
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