Clinical Trial: Daclizumab and Sirolimus to Treat Uveitis

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Combination Daclizumab/Sirolimus Therapy For the Induction of Immune Tolerance in Non-Infectious Intermediate and Posterior Uveitis

Brief Summary:

This study will examine whether the combination of the drugs daclizumab and sirolimus can effectively treat adults with uveitis, an eye inflammation. Daclizumab is a monoclonal antibody that is designed to prevent a specific chemical interaction needed for immune cells called lymphocytes to produce inflammation. Sirolimus is an immune-suppressing drug that also controls lymphocyte activity and is marketed to prevent organ rejection in kidney transplants.

Patients 18 years of age and older with non-infectious uveitis in one or both eyes who are being treated with daclizumab and have not had a relapse or disease flare for 6 months before entering this trial may be eligible for this study. Candidates are screened with a medical history and physical examination, blood tests, complete eye examination, and pregnancy test for women who can have children. Women of child-bearing potential who enroll in this study will have a pregnancy test every 12 weeks.

After enrollment, participants have the following additional exams:

• Fluorescein angiography: This test is done to check for abnormalities of eye blood vessels. A yellow dye is injected into an arm vein and travels to the blood vessels in the eyes. Pictures of the retina are taken with a special camera that flashes a blue light into the eye. The pictures show if any dye has leaked from the vessels into the retina, indicating possible abnormalities. This test is done at enrollment and after 1 year, unless additional tests are needed for medical management.
• Pelvic ultrasound and urine test: These tests are done at enrollment and after 1 year to check the kidneys, lymph nodes, and pelvic area.
• Blood tests: Blood tests are done at enrol
  

  Detailed Summary: We propose to investigate the possible efficacy of combination daclizumab and sirolimus therapy to induce peripheral immune tolerance in participants presenting with non-infectious intermediate and posterior uveitis. This will be performed using a Phase I/II pilot study. Subjects on daclizumab monotherapy will receive a 6 mg loading dose of oral sirolimus at week 0, followed by a 2 mg dose every other day for 2 weeks. If tolerated, the subject will be increased to a 2 mg daily dose. After one year of combination therapy, the subject will be tapered off daclizumab first and then sirolimus. The primary outcome will be the ability of the participant to be successfully tapered off daclizumab and sirolimus while their disease remains quiet (vitreous haze less than or equal to Trace) for 24 weeks on no systemic immunosuppressive medications (approximately week 134).
  Sponsor: National Eye Institute (NEI)
  

  Current Primary Outcome: Ability to taper off drug while disease remains quiet at week 108 while receiving no concomitant systemic immunosuppressive medications.
  
  

  Original Primary Outcome:
  
  

  Current Secondary Outcome: Number and severity of disease flares requiring changes in concomitant immunosuppressive medication.
  
  

  Original Secondary Outcome:
  
  Information By: National Institutes of Health Clinical Center (CC)
  

  Dates:
  Date Received: March 4, 2004
  Date Started: March 3, 2004
  Date Completion: July 18, 2008
  Last Updated: January 24, 2017
  Last Verified: July 18, 2008