HAT in Eye Complications of Behcet’s Disease

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Brief Title

HAT in Eye Complications of Behcet's Disease

Official Title

A Study to Investigate the Safety and Efficacy of HAT to Treat the Ocular Complications Related to Behcet's Disease

Brief Summary

      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.
    

Detailed Description

      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.
    

Study Phase

Phase 2

Study Type

Interventional




Condition

Behcet's Syndrome

Intervention

Daclizumab


Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

26

Start Date

July 1999

Completion Date

June 2004


Eligibility Criteria

        INCLUSION CRITERIA:

        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
        separate stratum.

        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.

        EXCLUSION CRITERIA:

        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
        years.

        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
        permitted.

        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.
      

Gender

All

Ages

N/A - N/A

Accepts Healthy Volunteers

No

Contacts

, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT00001865

Organization ID

990135

Secondary IDs

99-EI-0135


Study Sponsor

National Eye Institute (NEI)


Study Sponsor

, , 


Verification Date

June 2004