This study will examine whether the combination of the drugs daclizumab and sirolimus can
effectively treat adults with uveitis, an eye inflammation. Daclizumab is a monoclonal
antibody that is designed to prevent a specific chemical interaction needed for immune cells
called lymphocytes to produce inflammation. Sirolimus is an immune-suppressing drug that
also controls lymphocyte activity and is marketed to prevent organ rejection in kidney
Patients 18 years of age and older with non-infectious uveitis in one or both eyes who are
being treated with daclizumab and have not had a relapse or disease flare for 6 months
before entering this trial may be eligible for this study. Candidates are screened with a
medical history and physical examination, blood tests, complete eye examination, and
pregnancy test for women who can have children. Women of child-bearing potential who enroll
in this study will have a pregnancy test every 12 weeks.
After enrollment, participants have the following additional exams:
- 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. This test is done at enrollment and after 1
year, unless additional tests are needed for medical management.
- 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: Blood tests are done at enrollment and every 3 to 6 months for laboratory
and immunology study
Patients receive daclizumab subcutaneously (under the skin) or in infusions at regularly
scheduled visits for 52 weeks. At each treatment, blood pressure, pulse, breathing rate, and
temperature are monitored. After the first 52 weeks, patients whose disease remains quiet
increase the time between injections to 6 weeks and then to 8 weeks. Patients who are doing
well at this time may stop daclizumab.
One or 2 days after the first daclizumab treatment, patients receive 6 mg of sirolimus by
mouth. Their blood pressure, pulse, breathing rate, and temperature are monitored for at
least 60 minutes. Two days after the first dose, patients begin 2-mg maintenance doses every
other day for 2 weeks. If there are no intolerable side effects, the dose is increased to 2
mg daily for the next 2 weeks. Patients who have no intolerable side effects at that dose
continue the medication for another 4 weeks. Patients who experience intolerable side
effects may decrease the medication to every other day or withdraw from the study. After
week 78 of the study, if the daclizumab treatments are stopped, the sirolimus dose is
reduced within 8 weeks and may eventually be discontinued if the patient continues to do
Patients who experience any of the following will leave the study:
- Inflammation flare that requires concomitant treatment with additional systemic
immunosuppressive medications, such as prednisone or cyclosporine
- Disease flares more than twice in the first year
- Any disease flares in the second year
We propose to investigate the possible efficacy of combination daclizumab and sirolimus
therapy to induce peripheral immune tolerance in participants presenting with non-infectious
intermediate and posterior uveitis. This will be performed using a Phase I/II pilot study.
Subjects on daclizumab monotherapy will receive a 6 mg loading dose of oral sirolimus at
week 0, followed by a 2 mg dose every other day for 2 weeks. If tolerated, the subject will
be increased to a 2 mg daily dose. After one year of combination therapy, the subject will
be tapered off daclizumab first and then sirolimus. The primary outcome will be the ability
of the participant to be successfully tapered off daclizumab and sirolimus while their
disease remains quiet (vitreous haze less than or equal to Trace) for 24 weeks on no
systemic immunosuppressive medications (approximately week 134).
- INCLUSION CRITERIA:
Participant is 18 years of age or older.
Participant with uveitis in one or both eyes on daclizumab monotherapy without disease
flare in the past 6 months.
Participant agrees to use acceptable birth control methods throughout the course of the
study and for 6 months after completion of treatment with daclizumab or sirolimus.
Participant is able to understand and sign a consent form before entering the study.
Participant with a history of hypersensitivity to FK506 or sirolimus.
Participant who has had major surgery in the past 6 months.
Participant is pregnant or lactating.
Participant with active chronic or acute infections.
Participant with malignancy other than squamous cell carcinoma in situ.
Participant with uncontrolled hyperlipidemia at the time of enrollment.
Participant without VZV antibodies.
Participant without Hepatitis antibodies (anti-HAV or anti-HBc) AND with any one of the
following risk factors for acquiring hepatitis: IV drug abuse, male homosexual activity,
hemophilia, prostitution, or health care work.
Participant requiring systemic anti-fungal therapy with ketoconazole for whom no other
acceptable alternative anti-fungal therapy exists.