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.
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.
Patients must be 18 years of age or older for the primary randomized cohort.
Up to six additional patients under 18 but more than 6 years of age may enroll in a
Patients has ocular complications of Behcet's disease.
Patients is currently taking a minimum of 15 mg of prednisone, or cyclosporine, or
anti-metabolites, or any combination of these for the treatment of their intraocular
inflammatory disease and retinal vasculitis for at least the past 3 months.
Patients must have had at least two documented ocular attacks due to their Behcet's
disease involving the posterior segment.
Patients has normal renal or liver function or evidence of only mild abnormalities as
defined by the WHO criteria.
Patients has a neutrophil count above 750.
Patients agrees to use acceptable birth control methods throughout the course of the study
and for 6 months after completion of treatment if assigned to Zenapax. If patient is
assigned to placebo and has been unmasked, the patient need not practice birth control.
Patients is able to understand and sign a consent form before entering into the study.
Minor patients will be required to sign an assent.
Patients has 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 Zenapax.
Patients has significant active infection.
Patients has a history of cancer (other than non-melanoma skin cancer) within the past 5
Patient is pregnant or lactating.
Patients with significant symptomatic neurological disease which complicates evaluation of
neurological sequelae of Behcet's disease. This would include multiple sclerosis, stroke,
and other neurodegenerative disease are not eligible. Neuro-Behcet's disease would be
In the opinion of the treating physicians the ocular disease is end-stage, and there
would be no reasonable hope for an improvement in visual acuity.
Patient has used Latanoprost within two weeks prior to enrollment, or has a current or
likely need for Latanaprost during the course of the study.