Daclizumab Injections to Treat Non-Infectious Sight-Threatening Uveitis

Uveitis refers to intraocular inflammatory diseases that are an important cause of visual loss. Standard systemic immunosuppressive medications for uveitis can cause significant adverse effects. Consequently, an effective treatment with a safer side effect profile is highly desirable. Daclizumab is a humanized anti-Tac monoclonal antibody directed against the high affinity IL-2 receptor CD25 or Tac subunit. The IL-2 receptor system plays a central role in the induction of immune responses via activated T and B-lymphocytes, observed both in uveitis animal models and on the surface of human cells in patients with uveitis. Blocking this system impedes immune responses and can inhibit the development of local inflammatory responses. Previous studies using intravenous daclizumab treatments suggest that continuing daclizumab treatments at 1 mg/kg every 2-4 weeks may effectively control uveitis even after the complete withdrawal of standard immunosuppressive medications. Subcutaneous (SC) daclizumab injections at 1 and 2 mg/kg in healthy volunteers are well tolerated and have been shown to produce serum daclizumab trough levels comparable to intravenous treatments. This is an open-label, multi-center Phase II trial of SC daclizumab designed to provide information on current trial design feasibility as well as preliminary safety and efficacy data on 15 participants at 3 sites who are 6 years of age or older and who require standard systemic immunosuppression to control their non-infectious posterior or intermediate uveitis. The SC daclizumab treatments are given every 2 weeks for up to 6 months unless a safety endpoint requires study exit. A re-induction of SC daclizumab therapy may be permitted after an initial efficacy failure. Therapy begins with two induction treatments at 2 mg/kg (limit of 200 mg), followed by maintenance therapy at 1 mg/kg (limit of 100 mg). Beginning with the first SC daclizumab treatment, the initial immunosuppressive medication load will be tapered in a staggered fashion to a target level of 50% or less of the original dose within an 8 to 12-week period, if tolerated. After a preliminary efficacy evaluation at 12 weeks, further tapering and continued SC daclizumab therapy may continue as clinically indicated through the duration of the trial. The primary efficacy outcome is the maintenance of visual acuity with the simultaneous reduction of original immunosuppressive medication load. Primary safety measures are visual acuity and the occurrence of adverse events. Secondary outcome measures include anterior chamber and vitreous cells, vitreous haze, and questionnaire results.