Treatment of Systemic Lupus Erythematosus with CTLA4Ig

Principal Investigators:
Betty Diamond, Albert Einstein College of Medicine, NY
David Wofsy, University of California, San Francisco, CA

Abstract | Investigators | Background

Abstract

This study is a randomized, controlled, open-label, phase IIA trial to assess the safety of a single dose of CTLA4IgG4m (RG2077) in patients with active SLE and who are being treated with cyclophosphamide.

Participants will be randomized after receipt of cyclophosphamide infusion to either the treatment group or control group. A single 10-mg/kg dose of CTLA4-IgG4m (RG2077) will be administered by intravenous infusion over 1 hour to participants in the treatment group following the participant's scheduled infusion of cyclophosphamide. Patients will be monitored for 90 days after treatment.

The primary endpoint of this study is the safety of CTLA4-IgG4m (RG2077) therapy, which will be determined by the occurrence of adverse events. Adverse events will be assessed and recorded at regular intervals from the day of infusion through a 90-day period of follow-up after therapy.

The secondary endpoints of this study will assess renal function (measured by BUN, creatinine, urinary sediment, proteinuria, and creatinine clearance); lupus serology (ESR, anticardiolipin antibody, anti-dsDNA, C4, and CH50); SLE disease activity using the Safety of Estrogens in Lupus Erythematosus—National Assessment (SELENA) systemic lupus erythematosus disease activity index (SELENA SLEDAI), patient global assessment, and the immunogenicity and pharmacokinetics of CTLA4-IgG4m (RG2077).

The trial will be accompanied by an extensive set of studies that will permit us to learn (1) which individuals will have a therapeutic response to CTLA4-IgG4m (RG2077); (2) what the early immunologic indicators of a therapeutic response or of continuing disease activity are; (3) what the immunologic characteristics of a flare and of remission are; and (4) what the consequences of CTLA4-IgG4m (RG2077) are for protective immune responses. These studies will be carried out using the following techniques:

• DNA–HLA Typing/Genotyping
• Flow Cytometry Panel Staining
• Gene Expression Profiling (GeneChip™ & Real Time PCR)
• Serum and Urine Cytokine/Chemokine Analysis
• B-Cell Tetramer Analysis
• B-Cell ELISPOT Analysis
• Indoleamine 2,3-Dioxygenase Assay

Participating Investigators

	Betty Diamond, Albert Einstein College of Medicine, NY
	David Wofsy, University of California, San Francisco
	Anne Davidson, Albert Einstein College of Medicine, NY
	David Daikh, University of California, San Francisco

Background Articles

Reversal of Murine Lupus Nephritis with CTLA4Ig and Cyclophosphamide - J Immunol [go]