HAT in Eye Complications of Behcet's Disease
This study will evaluate the safety and effectiveness of Zenapax in controlling recurrent eye inflammations associated with Behcet's disease.
Behcet's disease is usually treated with corticosteroids to suppress inflammation. Other medicines such as methotrexate, cyclophosphamide, or azathioprine may also be used. These drugs all can have serious side effects, including liver or kidney damage. Zenapax is a monoclonal antibody that binds to certain proteins (receptors) on white blood cells, preventing them from interacting with a chemical called interleukin-2. Blocking this interaction prevents inflammation.
This study will include 20 patients who had unacceptable side effects from other medicines used to treat their disease; did not benefit from standard treatment; and refused standard treatment because of possible side effects of the medicines.
All patients in the study will continue to take their current medicines at the start of the study. In addition, one group of patients will receive Zenapax and a second group will receive a placebo. The drug or placebo will be infused into the vein at the start of the study and every two weeks for the next six weeks, and then every four weeks for the rest of the study period (24 months). Each infusion lasts about 15 minutes. Patients will have eye examinations at the time of every treatment, and medicines will be added if needed to control eye disease. Drugs will be tapered after six months in patients whose eye disease is quiet, and readjusted as necessary. Neither the doctors nor the patients will know who is receiving placebo and who is receiving Zenapax until the study ends.
Patients will be given a physical examination, medical history, eye examination, fluorescein angiography (special photographs of the retina to evaluate the blood vessels in the eye), and blood tests.
Zenapax was previously studied in 10 patients with uveitis with positive results. The patients were able to reduce the other medicines they were taking with minimal side effects.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Primary Purpose: Treatment
|Official Title:||A Study to Investigate the Safety and Efficacy of HAT to Treat the Ocular Complications Related to Behcet's Disease|
|Study Start Date:||July 1999|
|Estimated Study Completion Date:||June 2004|
The development of an ideal therapy to immunosuppress patients with Behcet's disease, a cause of endogenous uveitis and a major cause of acquired blindness in adults, is an important research goal. Corticosteroids remain the mainstay of therapy for intraocular inflammation; however, many patients are intolerant or resistant to corticosteroid therapy. Although the etiology of Behcet's disease is unknown, evidence suggests that an interleukin-2 receptor bearing auto-aggressive cells may play an important role in this disorder. Zenapax, a humanized anti-TAC (T-cell activated antigen) monoclonal antibody (HAT), has been utilized in Protocol # 96-EI-0096, a pilot Phase I/II study, to evaluate Zenapax administration in the treatment of patients with endogenous sight-threatening uveitis. Long-term results demonstrate a positive therapeutic trend in this trial. We propose a randomized masked pilot trial of Zenapax versus placebo. Twenty patients who are 18 years of age or older with Behcet's disease will be randomly assigned to receive either Zenapax or placebo in addition to their standard immunosuppressive therapy. After six months of quiescent disease, patients will be eligible to taper their standard immunosuppressive therapy. The primary purpose of the study is to investigate the safety and efficacy of Zenapax in controlling the recurrent, explosive nature of ocular manifestations in patients with Behcet's disease. Because this study is a Phase I/II study examining both efficacy and safety, primary outcomes for each are defined. The primary safety endpoint is one of the following: a) development of a life threatening complication, namely an exacerbation of systemic or neurological disease, or b) the development of a severe opportunistic infection. The primary efficacy outcomes of this study are based on the number of ocular attacks experienced and the amount of immunosuppressive medications over the 2 year study period, including the ability to taper the standard immunosuppressive therapy. Secondary efficacy outcomes include the level of inflammation as measured by vitreous haze and anterior chamber cells and flare, the presence or absence of cystoid macular edema, the change from baseline in visual acuity, and quality of life issues as measured through questionnaires.
|United States, Maryland|
|National Eye Institute (NEI)|
|Bethesda, Maryland, United States, 20892|