A Phase I Clinical Trial of Immunotherapy With Humanized LL2 IgG (Epratuzumab) in Patients With Systemic Lupus Erythematosus
This is a pilot study to evaluate the safety and tolerance of hLL2 (epratuzumab), a
humanized anti-CD22 monoclonal antibody, in patients with systemic lupus erythematosus
B-lymphocytes play a major role in initiating and maintaining the underlying
immunopathological mechanisms of SLE. In addition to producing autoantibodies, they also
serve as antigen presenting cells and are able to disrupt peripheral T lymphocyte tolerance.
Furthermore, B lymphocyte depletion ameliorates disease activity in animal models of SLE.
Therefore, targeted depletion of B-lymphocytes may be of therapeutic benefit in human SLE.
hLL2 (epratuzumab) is a humanized monoclonal antibody that binds to CD22, a surface antigen
expressed exclusively on B-lymphocytes. Clinical studies in patients with B cell lymphomas
have shown that epratuzumab is safe and well tolerated across a wide range of doses.
Although the exact mechanism is unknown, indirect evidence suggests that the antibody is
depleting target B lymphocytes. Epratuzumab is made available by Immunomedics, Inc., and
will be used under an investigator (NIH)-initiated IND.
In this open-label, Phase I study, up to 20 patients with moderately active SLE may be
enrolled. Patients will be treated with weekly infusions of hLL2 in one of three different
dosing groups [(240 mg/m(2), 360 mg/m(2), 480 mg/m(2)] for 4 weeks, and followed for 8
weeks after the last dose.
The primary objective is to determine the safety and tolerability of hLL2 in patients with
SLE. In addition to safety data, clinical and laboratory data will also be collected for
preliminary evaluation of the effectiveness of hLL2 in SLE and to assess the effect of hLL2
on B and T lymphocytes in the lymphoid organs and the peripheral blood. If the treatment is
safe and there is preliminary evidence of efficacy, this regimen could be used in controlled
trials in the future.
Endpoint Classification: Safety Study, Primary Purpose: Treatment
United States: Federal Government
|National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)||Bethesda, Maryland 20892|