Combination Daclizumab/Denileukin Diftitox to Treat Uveitis
Condition: Non-infectious Intermediate and Posterior Uveitis
MeSH terms: Uveitis; Uveitis, Posterior
Study type: Interventional
Phase: Phase 2

Summary: 
      This study will determine whether treatment with a combination of the drugs daclizumab and
      denileukin diftitox can eliminate the need for long-term daclizumab treatment in adult
      patients with uveitis. Denileukin diftitox kills white blood cells called lymphocytes that
      cause inflammation and may be the cause of uveitis.

      Patients 18 years of age and older with uveitis in one or both eyes who are on daclizumab
      therapy and have not had a disease flareup in 6 months may be eligible for this study.
      Candidates are screened with a medical history, physical examination, eye examination
      (including vision test, examination of the front of the eye, and pupil dilation for
      examination of the retina at the back of the eye), blood tests and a questionnaire about
      their vision and daily activities.

      After screening, participants undergo the following procedures:

        -  Daclizumab/ denileukin diftitox treatment. Patients receive their regular dose of
           daclizumab intravenously (through a vein). The interval between doses is increased by 1
           week after each dose. When the doses are 10 weeks apart, the daclizumab is stopped.
           Patients who experience a flare or uveitis are treated with intravenous denileukin
           diftitox and possibly local injections of steroids around the eye or increasing or
           adding other medicines as needed to control the uveitis.

        -  Fluorescein angiography to look for blood vessel abnormalities in the eyes. A yellow dye
           is injected into an arm vein and travels to the blood vessels in the eyes. Pictures of
           the retina (the back portion of the eye) 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.

        -  Ultrasound and urine tests at enrollment and after 1 year to check kidneys, lymph nodes
           and pelvic area.

        -  Blood tests at enrollment and every 3-6 months for laboratory and immunology tests and
           other research tests on blood cells to examine the immune response.

        -  Follow-up visits approximately every 6 weeks for 2 years for repeat examinations to
           determine the response to treatment and drug side effects.
    

Detailed description: 
      We propose to investigate the possible efficacy of combination daclizumab and denileukin
      diftitox 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 whose disease is controlled on daclizumab therapy will have their
      daclizumab-dosing interval progressively increased by one-week increments. If and when they
      experience signs or symptoms of an ocular flare, they will be treated with denileukin
      diftitox, 24 hours after which they will receive their usual dose of daclizumab. Participants
      may receive up to 12 such cycles of daclizumab/denileukin diftitox therapy. When the
      daclizumab-dosing interval is 10 weeks long or less than 10% of their CD4 T cell CD25 is
      occupied by daclizumab, therapy will be discontinued. Following discontinuation of daclizumab
      patients will be followed for recurrence of ocular disease. Failure to reach this study point
      after 12 cycles or disease recurrence following discontinuation of therapy will constitute a
      study failure. The primary outcome will be the ability of the participant to be successfully
      tapered off daclizumab while their disease remains quiet (vitreous haze less than or equal to
      Trace) at week 104 while receiving no concomitant systemic immunosuppressive medications.
    

Intervention name(s): Daclizumab
Intervention type(s): Drug
Intervention MeSH terms: Daclizumab
Primary purpose: Treatment
Keywords: T Lymphocytes; IL-2 Conjugate; CD25; T Regulatory Cells; Autoimmunity; Uveitis; Daclizumab; Denileukin Diftitox; Immune Tolerance; T Cell