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

This study has been completed.
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00130637
First received: August 12, 2005
Last updated: November 24, 2010
Last verified: November 2010
  Purpose

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.


Condition Intervention Phase
Anterior Uveitis
Arthritis, Juvenile Idiopathic
Iritis
Immunosuppression
Drug: Daclizumab
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Treatment of Active Anterior Uveitis Associated With JIA, Using Humanized Anti-Tac (HAT, Daclizumab)

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Number of Participants Reporting an Adverse Event [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]
    Safety of acute daclizumab use in JIA-associated uveitis was assessed through serious adverse events (SAE).

  • Number of Participants With a Two-step Reduction in Inflammation [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    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.


Enrollment: 6
Study Start Date: August 2005
Study Completion Date: May 2008
Primary Completion Date: May 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Daclizumab Drug: Daclizumab
Other Name: Human Anti-Tac

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   6 Years to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00130637

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Robert Nussenblatt, M.D./National Eye Institute, National Institutes of Health
ClinicalTrials.gov Identifier: NCT00130637     History of Changes
Other Study ID Numbers: 050208, 05-EI-0208
Study First Received: August 12, 2005
Results First Received: August 12, 2010
Last Updated: November 24, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institutes of Health Clinical Center (CC):
Anterior Uveitis
Arthritis, Juvenile Idiopathic
Daclizumab
Iritis
Immunosuppression
Chronic Inflammatory Eye-Disease
Juvenile Idiopathic Arthritis

Additional relevant MeSH terms:
Arthritis
Iritis
Uveitis
Chorioretinitis
Uveitis, Anterior
Iridocyclitis
Arthritis, Juvenile
Joint Diseases
Musculoskeletal Diseases
Iris Diseases
Uveal Diseases
Eye Diseases
Panuveitis
Retinitis
Retinal Diseases
Choroiditis
Choroid Diseases
Uveitis, Posterior
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Daclizumab
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 28, 2014