Presented at:
56th American Academy of Neurology, San Francisco, CA,
April 27,
2004
Phase I Trial of CTLA4Ig Treatment in MS
Samia J. Khoury, Kasia Bourcier, Guy Buckle, Michelle Bikowski, Boston, MA, Patrice Rioux, Karen Jauregui
Waltham, MA
OBJECTIVE: To determine the safety of RG2077 in patients with multiple sclerosis.
BACKGROUND: Multiple sclerosis (MS) is an autoimmune disease of the central nervous system initiated by autoreactive CD4+ T cells recognizing and responding to myelin antigens. Blocking CD28-B7 costimulation by CTLA4-Ig has been used in several models of autoimmune disease and transplantation. Human trials with another CTLA4Ig agent have been reported in psoriasis, and rheumatoid arthritis. RG2077 (from Repligen) is a recombinant protein of CTLA4 (cytolytic-T-lymphocyte associated antigen-4) fused to the heavy chain constant region of the human immunoglobulin of the IgG4 isotype. The gene sequence encoding the immunoglobulin portion has been altered to remove the functional properties of binding the Fc receptor and fixation of complement.
DESIGN/METHODS: We performed an open-label, dose escalation study in relapsing-remitting MS patients. The subjects were divided amongst four dose groups: 2.0 mg/kg,10.0 mg/kg, 20.0 mg/kg and 35.0 mg/kg. Each subject received one IV infusion of RG2077. Safety assessments included blood studies, a MRI, a neurological examination and physical examination. Mechanistic studies were performed at baseline, 1 week, 1 month and 3 months post infusion. The study was supported by the Immune Tolerance Network.
RESULTS: The results of the safety data and analysis of the immunologic effects of the treatment will be presented.