Human Anti-Tac (Daclizumab) to Treat Juvenile Idiopathic Arthritis (JIA)-Associated Uveitis
Condition: Anterior Uveitis; Arthritis, Juvenile Idiopathic; Iritis; Immunosuppression
MeSH terms: Arthritis; Arthritis, Juvenile; Uveitis; Uveitis, Anterior; Iridocyclitis; Iritis
Intervention: Daclizumab
Intervention MeSH terms: Daclizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 6.0
Sex: All
Minimum age: 6 Years
Maximum age: 18 Years
Healthy volunteers: No
Keywords: Anterior Uveitis; Arthritis, Juvenile Idiopathic; Daclizumab; Iritis; Immunosuppression; Chronic Inflammatory Eye-Disease; Juvenile Idiopathic Arthritis

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 retinal thickening.

        -  Stereoscopic color fundus photography to examine the back of the eye. The pupils are
           dilated with eye drops to examine and photograph the back of the eye.

      Upon entering the study, participants receive a 90-minute infusion of daclizumab through a
      catheter (plastic tube) placed in an arm vein. They return to the clinic after 14 days and
      again after 28 days for repeat eye examinations, blood tests, and daclizumab infusions. Four
      weeks after the third infusion, patients are examined for response to treatment. Those who
      have benefited from daclizumab may continue receiving monthly infusions of the drug for up to
      one year. A blood test and eye examination are done at the time of each infusion. Patients
      whose disease has remained active 12 weeks after the first infusion are taken off the study
      and treated with other medications.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

               1. Participant is from 6 to 18 years of age, inclusive;

               2. Participant has a diagnosis of non-infectious uveitis associated juvenile
                  idiopathic arthritis (JIA) requiring treatment to control their intraocular
                  inflammatory disease with anti-inflammatory medications, systemic and/or topical
                  at high frequency intervals (greater than or equal to 3 times a day).

               3. Participant's uveitis is considered active on current regimen

               4. Participant has uveitis with at least a grade of 1+ for anterior chamber cells in
                  at least one eye

               5. Participant's uveitis is currently treated or untreated at the time of enrollment

               6. Participant has visual acuity in at least one eye of 20/640 or better (Early
                  Treatment Diabetic Retinopathy Study (ETDRS) or Electronic Visual
                  Acuity-Amblyopia Treatment Study (EVA-ATS), log minimum angle of resolution
                  (logMAR) less than 1.54).

               7. Participant has normal renal or liver function or evidence of no worse than mild
                  abnormalities as defined by the "Common Toxicity Criteria for Adverse Events"
                  (CTCAE) version 3.0, including:

                  Test Parameter Age (yrs) Pediatric Mild Limit

                  Serum creatinine 6-12 1.0 mg/dL

                  13-18 1.6 mg/dL

                  Proteinuria 6-18 3 g/L

                  Uric acid 6-18 9.9 mg/dL

                  Blood Urea Nitrogen (BUN) 6-18 2.0 upper normal limit

                  Aspartate aminotransferase (Serum glutamic-oxaloacetic transaminase) (AST (SGOT))
                  6-18 2.5 upper normal limit

                  Alanine aminotransferase (Serum glutamic pyruvic transaminase) (ALT (SGPT)) 6-18
                  2.5 upper normal limit

               8. Participant agrees not to undergo elective ocular surgery (e.g., cataract
                  extraction) for the first 6 months of the study.

               9. Participant has an absolute neutrophil count above 750.

              10. Participant is not currently pregnant or lactating.

              11. Participant with reproductive potential and who is sexually active agrees to use
                  acceptable birth control methods throughout the course of the study and for 6
                  months after completion of treatment.

              12. All participants at enrollment has a parent or legal guardian who is able to
                  understand and sign a consent form on their behalf before entering into the
                  study, and participant signs an assent as a minor.

              13. Meet American College of Rheumatology Criteria for Juvenile Rheumatoid Arthritis
                  (JRA)/JIA (Appendix) but is not newly diagnosed, and has had systemic treatment
                  for their uveitis.

              14. Be able to undergo slit lamp biomicroscopy for assessment of anterior chamber
                  cells.

              15. Be able to comply with the study requirements.

              16. Be up to date on all recommended childhood immunizations.

        EXCLUSION CRITERIA:

          1. Participants under the age of 6 years will not be enrolled in the study due to the
             reported higher incidence of adverse events related or unrelated to the administration
             of daclizumab in post-transplant pediatric studies compared to children over age 6.

          2. Participants who had received previous treatment with an IL-2 directed monoclonal
             antibody or any other investigational agent that would interfere with the ability to
             evaluate the safety, efficacy or pharmacokinetics of daclizumab.

          3. Participants with a history or diagnosis of Behcet's disease.

          4. Participant has a significant active infection.

          5. Participant has a history of cancer (other than a non-melanoma skin cancer) diagnosed
             within the past 5 years.

          6. Participant has used latanoprost (Xalatan) within two weeks prior to study enrollment
             or has a likely need.

          7. Participant for whom administration of fluorescein dye is medically contraindicated.

          8. Have a media opacity that precludes assessment of anterior chamber inflammation.

          9. Be a female who is pregnant or lactating.

         10. Refuse to use contraception during the study and 6 months after termination of active
             study therapy, if child-bearing or fathering potential exists.

         11. Have active serious infections or a history of recurring serious infections.

         12. Evidence of spondyloarthropathy or enthesopathy.

         13. Have active joint or systemic inflammation requiring immediate addition or increase in
             systemic anti-inflammatory medications.