Clinical Trial: Human Anti-Tac (Daclizumab) to Treat Juvenile Idiopathic Arthritis (JIA)-Associated Uveitis

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

Official Title: Treatment of Active Anterior Uveitis Associated With JIA, Using Humanized Anti-Tac (HAT, Daclizumab)

Brief Summary:

This study will examine the safety and effectiveness of a monoclonal antibody called humanized anti-Tac (HAT, also called daclizumab) to treat children and adolescents with uveitis (chronic inflammatory eye disease) associated with juvenile idiopathic arthritis (JIA). Monoclonal antibodies are genetically engineered proteins made in large quantities and directed against a specific target in the body. The HAT antibody is designed to prevent a specific chemical interaction needed for immune cells to produce inflammation. Current treatments for uveitis include steroids and immune-suppressing drugs. These treatments do not always work or they may cause significant side effects. This study will determine whether daclizumab can improve uveitis in children and reduce the need for other medicines.

Patients between 6 and 18 years of age with active non-infectious JIA-associated uveitis requiring treatment with anti-inflammatory medications as often as three times a day or more may be eligible for this study.

Each candidate is screened with a medical history, physical examination, blood tests, eye examination, and the following specialized tests:

  • Fluorescein angiography to evaluate the eye's 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 using a camera that flashes a blue light into the eye. The pictures show if any dye has leaked from the vessels into the retina, indicating the presence of inflammation.
  • Optical coherence tomography to measure retinal thickness. The eyes are examined through a machine that produces cross-sectional pictures of the retina. These measures are repeated during the study to determine changes, if any, in

    Detailed Summary:

    Pediatric uveitis represents 5-10 % of all patients with uveitis. Uveitis refers to intraocular inflammatory diseases. The most common type of non-infectious pediatric uveitis, associated with a systemic disease, is JIA-associated chronic, anterior uveitis. Therapeutic considerations for pediatric uveitis are often very challenging. Current therapeutic modalities include corticosteroids and other immunosuppressive agents. These modalities are not always effective at controlling the disease. In addition they can also be associated with a higher rate of ocular side effects. To further add to this challenge, pediatric uveitis has a higher rate of ocular complications, even with the current therapies. Consequently, an effective treatment with a safer side effect profile is highly desirable. Daclizumab is a humanized monoclonal antibody directed against the high affinity interleukin-2 (IL-2) receptor CD25 or Tac subunit. The IL-2 receptor system plays a central role in mediating immune responses. Blocking this system impedes immune responses and can inhibit local inflammatory responses, including uveitis. Pilot studies using intravenous or subcutaneous daclizumab treatments suggest that daclizumab treatments at 2 mg/kg every 2-4 weeks for quiescent uveitis may effectively replace the other immunosuppressive medications in a majority of cases.

    Because we have little experience using daclizumab for active uveitis in a pediatric population, this feasibility study will enroll seven study participants that would normally be treated with systemic, high-dose corticosteroids or other cytotoxic, systemic immunosuppressive medications. Since daclizumab for other indications can be tolerated with repeated dosing at 8-10 mg/kg, we will administer daclizumab to reach high serum levels with a pair of doses at 8 mg/kg and 4 mg/kg two weeks apart. The primary objective of this study is to col
    Sponsor: National Eye Institute (NEI)

    Current Primary Outcome:

    • Number of Participants With a Two-step Reduction in Inflammation [ Time Frame: 12 weeks ]
      Number of participants with a two-step reduction (or down to 0 out of a scale of 0 to 4+) of anterior chamber (AC) inflammation according to Standardization of Uveitis Nomenclature (SUN) criteria, while on a topical corticosteroid schedule of less than 3 times a day. Grade 0 is the best score on this scale with <1 cell in the field and 4+ is the worst score on this scale with >50 cells in the field.
    • Number of Participants Reporting a Serious Adverse Event (SAE) [ Time Frame: 52 weeks ]
      Safety of acute daclizumab use in JIA-associated uveitis was assessed through serious adverse events (SAE).


    Original Primary Outcome:

    Current Secondary Outcome:

    Original Secondary Outcome:

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

    Dates:
    Date Received: August 12, 2005
    Date Started: August 2005
    Date Completion:
    Last Updated: January 27, 2017
    Last Verified: January 2017