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.
This pilot study has permitted enrollment of up to 12 adults with non-infectious intermediate
or posterior uveitis who require treatments to maintain visual function. This extended
protocol began with an evaluation of the safety and potential efficacy of intravenous (IV)
daclizumab treatments for uveitis while reducing or eliminating standard medications
commensurate with the standard of care. As subcutaneous (SC) daclizumab treatments become
available, eligible participants will be offered continuing daclizumab treatments using the
new SC formulation, though they may elect to remain on the IV treatments. If the therapeutic
benefit is sustained using the SC formulation, maintenance therapy will continue as
clinically indicated. Participants who repeatedly fail the SC therapy will be permitted to
revert to the IV daclizumab regimen they previously used, or may exit the study as treatment
failures. SC treatments begin with a short SC induction at 2 mg/kg followed by 1 mg/kg
treatments on a 4-week schedule as the protocol originally specified. Participants will be
monitored routinely when each dose is received and additionally will participate in
pharmacokinetic studies to monitor SC formulation bioavailability.
Daclizumab is a humanized anti-Tac monoclonal antibody (HAT, Zenapax) that interferes with
inflammatory processes by its involvement with the interleukin 2 receptor (IL-2R). During the
first 5 years of this study, only an IV product was available. The SC formulation is now
available containing the same daclizumab drug product. Preliminary studies indicate that the
SC formulation is well tolerated by normal control subjects and other autoimmune disease
patients at repeated doses up to 2 mg/kg.
The primary objectives are to examine the safety and potential efficacy of IV and later, SC
daclizumab, while continuing to reduce other immunosuppressive medications commensurate with
the standard of care. Primary safety outcomes are the discontinuation of study therapy due to
reduced vision or the occurrence of adverse events. Secondary outcome measures include visual
acuity and the grading of immunosuppressive medications, anterior chamber and vitreous cells,
and vitreous haze.