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

NCT00130637 | Completed Phase 2 Results DMC

• 2 other identifiers: 05020805-EI-0208
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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 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.

Conditions

Anterior Uveitis; Arthritis, Juvenile Idiopathic; Iritis; Immunosuppression

Keywords

Anterior Uveitis; Arthritis, Juvenile Idiopathic; Daclizumab; Iritis; Immunosuppression; Chronic Inflammatory Eye-Disease; Juvenile Idiopathic Arthritis

Outcome Measures

Primary Outcomes (2)

• Number of Participants With a Two-step Reduction in Inflammation

  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.

  12 weeks

• Number of Participants Reporting a Serious Adverse Event (SAE)

  Safety of acute daclizumab use in JIA-associated uveitis was assessed through serious adverse events (SAE).

  52 weeks

Study Arms (1)

Daclizumab

EXPERIMENTAL

IV daclizumab

Drug: Daclizumab

Interventions

Daclizumab DRUG

Also known as: Human Anti-Tac

Daclizumab

Eligibility Criteria

• Age: 6 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Participant is from 6 to 18 years of age, inclusive;
• 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).
• Participant's uveitis is considered active on current regimen
• Participant has uveitis with at least a grade of 1+ for anterior chamber cells in at least one eye
• Participant's uveitis is currently treated or untreated at the time of enrollment
• 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).
• 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
• 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

You may not qualify if:

• 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.
• 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.
• Participants with a history or diagnosis of Behcet's disease.
• Participant has a significant active infection.
• Participant has a history of cancer (other than a non-melanoma skin cancer) diagnosed within the past 5 years.
• Participant has used latanoprost (Xalatan) within two weeks prior to study enrollment or has a likely need.
• Participant for whom administration of fluorescein dye is medically contraindicated.
• Have a media opacity that precludes assessment of anterior chamber inflammation.
• Be a female who is pregnant or lactating.
• Refuse to use contraception during the study and 6 months after termination of active study therapy, if child-bearing or fathering potential exists.
• Have active serious infections or a history of recurring serious infections.
• Evidence of spondyloarthropathy or enthesopathy.
• Have active joint or systemic inflammation requiring immediate addition or increase in systemic anti-inflammatory medications.

Sponsors & Collaborators

• National Eye Institute (NEI): lead
• The Emmes Company, LLC: collaborator

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (2)

• Chylack LT Jr. The ocular manifestations of juvenile rheumatoid arthritis. Arthritis Rheum. 1977 Mar;20(2 Suppl):217-23.

  PMID: 263899 BACKGROUND

• Sen HN, Levy-Clarke G, Faia LJ, Li Z, Yeh S, Barron KS, Ryan JG, Hammel K, Nussenblatt RB. High-dose daclizumab for the treatment of juvenile idiopathic arthritis-associated active anterior uveitis. Am J Ophthalmol. 2009 Nov;148(5):696-703.e1. doi: 10.1016/j.ajo.2009.06.003. Epub 2009 Aug 6.

  PMID: 19664754 RESULT

MeSH Terms

Conditions

Uveitis, Anterior; Arthritis, Juvenile; Iritis

Interventions

Daclizumab

Condition Hierarchy (Ancestors)

Panuveitis; Uveitis; Uveal Diseases; Eye Diseases; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Iris Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

The results of this trial need to be interpreted cautiously because of the small number of patients, the heterogeneity of the patient population (such as one participant with systemic JIA), and the nonrandomized and unmasked nature of the trial.

Results Point of Contact

• Title: H. Nida Sen, MD, MHS
• Organization: National Eye Institute, NIH

senh@nei.nih.gov

301-435-5139

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 12, 2005
• First Posted: August 15, 2005
• Study Start: August 1, 2005
• Primary Completion: May 1, 2008
• Study Completion: May 1, 2008
• Last Updated: January 30, 2017
• Results First Posted: September 29, 2010

Record last verified: 2017-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)