Daclizumab Injections to Treat Non-Infectious Sight-Threatening Uveitis
This study will examine the safety and effectiveness of a monoclonal antibody called daclizumab in treating uveitis, an eye inflammation. Monoclonal antibodies are genetically engineered proteins made in large quantities and directed against a specific target in the body. Daclizumab is designed to prevent a specific chemical interaction needed for immune cells called lymphocytes to produce inflammation. In an ongoing NIH study of 10 adults with uveitis, 8 patients were able to decrease corticosteroids and other immunosuppressive medicines they were taking while receiving daclizumab for months or even years. The study will be conducted at three different sites, including the NIH Clinical Center.
Patients 6 years of age and older with non-infectious uveitis of at least 3 months' duration who require treatment with immune suppressing medicines, such as prednisone, cyclophosphamide, cyclosporine, azathioprine, methotrexate, or others, may be eligible for this study. Candidates will be screened with a medical history and physical examination, blood tests, complete eye examination, and a questionnaire about the patient's vision and daily activities.
Participants will come to the study center every 2 weeks for treatment and evaluation. Daclizumab treatments are given by injection under the skin, usually in the arm. Patients will receive a maximum of 28 treatments over a 1-year period. Treatment may be extended for a few months while other participants reach their 1-year mark. The first two induction treatments are at a higher dose (2 mg/kg of body weight) than the maintenance dose of 1 mg/kg. After the first daclizumab treatment, other uveitis medications will be tapered, one at a time. If the disease remains quiet, these drugs may eventually be stopped completely.
For the first 6 months, all patients will receive daclizumab injections and evaluations every 2 weeks. After that, if other medications have been reduced and vision has remained stable, treatments and evaluations may be spread out to every 3 or 4 weeks. Over time, fewer tests may be required during the biweekly examinations if the patient is doing well, but nearly all the examinations done at screening will be repeated at 3-month intervals. If inflammation or vision loss occurs during drug tapering, appropriate treatment will be administered. If the vision loss is too great, the patient will be treated with steroids or other medicines and taken off the study.
Additional, special tests done at selected study centers include the following:
- Fluorescein angiography: This test is done to check for abnormalities of eye 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 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.
- Pelvic ultrasound and urine test: These tests are done at enrollment and after 1 year to check the kidneys, lymph nodes, and pelvic area.
- Blood tests: Additional blood tests are done at enrollment and every 3 to 6 months for laboratory and immunology study.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Primary Purpose: Treatment
|Official Title:||Evaluation of Subcutaneous Daclizumab Treatments in Patients With Non-Infectious Sight-Threatening Uveitis: A Multicenter, Open-Label, Phase II Study|
|Study Start Date:||August 2002|
|Estimated Study Completion Date:||October 2004|
Uveitis refers to intraocular inflammatory diseases that are an important cause of visual loss. Standard systemic immunosuppressive medications for uveitis can cause significant adverse effects. Consequently, an effective treatment with a safer side effect profile is highly desirable. Daclizumab is a humanized anti-Tac monoclonal antibody directed against the high affinity IL-2 receptor CD25 or Tac subunit. The IL-2 receptor system plays a central role in the induction of immune responses via activated T and B-lymphocytes, observed both in uveitis animal models and on the surface of human cells in patients with uveitis. Blocking this system impedes immune responses and can inhibit the development of local inflammatory responses. Previous studies using intravenous daclizumab treatments suggest that continuing daclizumab treatments at 1 mg/kg every 2-4 weeks may effectively control uveitis even after the complete withdrawal of standard immunosuppressive medications. Subcutaneous (SC) daclizumab injections at 1 and 2 mg/kg in healthy volunteers are well tolerated and have been shown to produce serum daclizumab trough levels comparable to intravenous treatments.
This is an open-label, multi-center Phase II trial of SC daclizumab designed to provide information on current trial design feasibility as well as preliminary safety and efficacy data on 15 participants at 3 sites who are 6 years of age or older and who require standard systemic immunosuppression to control their non-infectious posterior or intermediate uveitis. The SC daclizumab treatments are given every 2 weeks for up to 6 months unless a safety endpoint requires study exit. A re-induction of SC daclizumab therapy may be permitted after an initial efficacy failure. Therapy begins with two induction treatments at 2 mg/kg (limit of 200 mg), followed by maintenance therapy at 1 mg/kg (limit of 100 mg). Beginning with the first SC daclizumab treatment, the initial immunosuppressive medication load will be tapered in a staggered fashion to a target level of 50% or less of the original dose within an 8 to 12-week period, if tolerated. After a preliminary efficacy evaluation at 12 weeks, further tapering and continued SC daclizumab therapy may continue as clinically indicated through the duration of the trial. The primary efficacy outcome is the maintenance of visual acuity with the simultaneous reduction of original immunosuppressive medication load. Primary safety measures are visual acuity and the occurrence of adverse events. Secondary outcome measures include anterior chamber and vitreous cells, vitreous haze, and questionnaire results.
|United States, Maryland|
|National Eye Institute (NEI)|
|Bethesda, Maryland, United States, 20892|