Study of Efalizumab Combined With Intravitreal Ranibizumab in the Treatment of Age-Related Macular Degeneration
Status:
Withdrawn
Trial end date:
1969-12-31
Target enrollment:
Participant gender:
Summary
Efalizumab is an immunosuppressive recombinant humanized IgG1 monocolonal antibody (150 Kd)
that binds to human CD11a (1) and is used for the treatment of plaque psoriasis. Efalizumab
was derived from the humanization of the murine efalizuman monoclonal antibody MHM24, which
recognizes human and chimpanzee CD11a. Humanization of MHM24 was accomplished by grafting the
murine complementarity determining regions (hypervariable region) into consensus human IgG1/
heavy and light chain sequences (Werther et al 1996). These same consensus human
immunoglobulin sequences have been successfully used in the humanization of other murine
antibodies, including those targeted to HER2 and IgE. Efalizumab inhibits the binding of
LFA-1 to intercellular adhesion molecule-1 (ICAM-1) thereby inhibiting the adhesion of
leukocytes to other cell types.
Ranibizumab is a recombinant, humanized, Fab fragment of a mouse monoclonal antibody targeted
against VEGF. As VEGF binds to cellular receptors, it stimulates angiogenesis and vascular
leakage. Blockade of VEGF by ranibizumab leads to reduced stimulation of cell proliferation
and permeability resulting in inhibition of angiogenesis and decreased leakage. Ranibizumab
intravitreal administration in neovascular AMD patients has been shown to effectively reduce
vascular leakage and growth of CNV and to stabilize or improve visual function.
To further improve visual acuity, a combination therapy using efalizumab and ranibizumab is
proposed. Efalizumab could target the adhesion factors that precede angiogenesis and improve
the outcome for AMD patients in combination with the anti-VEGF agent, Ranibizumab.