October 1, 2012
The newly formed SMT for the ITN055AI CALIBRATE study in lupus nephritis met in Bethesda in late August to review and discuss the project timeline and scientific rationale and to begin protocol development. This meeting follows the recent milestone of the ITN034AI ACCESS lupus nephritis study enrolling 137 participants 10 weeks ahead of schedule. Many of the ACCESS team members are also on the CALIBRATE study team including the Protocol Study Chairs: Cynthia Aranow, Maria Dall’Era, Betty Diamond, and David Wofsy. Team members from the ITN include: Stephanie Chan, Eduard Chani, Mike Howell, Barb Nagaraj, Debs Phippard, Nancy Skeeter, Dawn Smilek, and Patti Tosta. Members from NIAID include: Christine Czarniecki, Linna Ding, Wendy Gao, and Jui Shah. Jim Rochon from Rho attended the meeting as well.
Lupus nephritis is a serious manifestation of systemic lupus erythematous (SLE) which is an autoimmune connective tissue disease that affects multiple organ systems. Women are affected predominantly, including young women of childbearing age, with peak age of onset between late teens and early 40s. SLE is characterized by autoantibodies, including antibodies to dsDNA, and by abnormal B cell activation and differentiation, indicating that B cell depleting and modulating therapies could be beneficial in treating SLE. Belimumab, an inhibitor of B-cell activating factor (BAFF), has recently been FDA-approved for the treatment of SLE, and rituximab, a B-cell depleting agent, has been recommended for treatment of lupus nephritis that is refractory to standard immunosuppression.
The primary hypothesis being tested in this study is that treatment of proliferative lupus nephritis with rituximab and cyclophosphamide, followed by BAFF inhibition with belimumab will result in reduced selection of autoreactive B cells in the reconstituted B cell repertoire. Demonstration of improved short and long term clinical responses that are potentially achieved by this approach would be highly significant and a major advance as patients would experience better outcomes with less long term exposure to immunosuppressive medications.
The study is projected to enroll 90 participants with the first participant enrolled in July 2013. The enrollment period for the study is 104 weeks with the last participant projected to be enrolled in June 2015.
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