A Pilot Study to Investigate Ustekinumab (STELARA) for the Treatment of Active Sight-Threatening Uveitis
A Pilot Study to Investigate Ustekinumab (STELARA) for the Treatment of Active Sight-Threatening Uveitis
Background:
Uveitis is an inflammation of the eye that can cause vision loss. It is treated with medications and sometimes surgery. However, in many people, treatment does not always prevent loss of vision. A new medication, ustekinumab, reduces inflammation in patients with other inflammatory diseases. Therefore, it might be helpful in treatment of uveitis.
Objective:
To see if ustekinumab is safe and can help people with uveitis.
Eligibility:
People ages 18 and older with uveitis
Design:
Participants will be screened with:
Medical and eye disease history
Physical exam
Eye exam: The pupil is dilated with eye drops. A machine scans the back of the eye. Pictures are taken of the inside of the eye.
Blood and urine tests
Tuberculosis test
Participants will have 6 clinic visits over 28 weeks. Visits lasts 2-3 hours and include:
Participants will have their uveitis monitored and receive standard uveitis care during the study.
Objective: 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 and many patients continue to experience disease flare-ups. Ustekinumab is a human IL-12 and -23 antagonist. The involvement of IL-12 and IL-23 in the pathophysiology of uveitis and other autoimmune diseases known to be associated with uveitis suggests that ustekinumab could be a potential treatment for uveitis. The study objective is to investigate the safety, tolerability and potential efficacy of ustekinumab as a possible treatment for active intermediate uveitis, posterior uveitis or panuveitis.
Study Population: The first cohort will consist of five participants with active intermediate uveitis, posterior uveitis or panuveitis who meet the inclusion criteria. The second cohort will include up to four participants with active intermediate uveitis, posterior uveitis or panuveitis who meet the inclusion criteria. Up to eleven participants may be enrolled, as up to two participants may be accrued in the second cohort to account for participants who withdraw from the study prior to Week 16.
Design: This is a prospective, non-randomized, uncontrolled, two-arm pilot study to evaluate of ustekinumab as a possible treatment for active intermediate uveitis, posterior uveitis or panuveitis. Five participants in the first cohort will receive a 90 mg subcutaneous (SC) injection of ustekinumab at baseline and a second and third injection at Week 4 and 8 for a total of 3 injections. For the second cohort, up to four participants will receive an initial high, weight-based dose of ustekinumab via intravenous (IV) injection (up to 55 kg, 260 mg (2 vials); greater than 55 kg to 85 kg, 390 mg (3 vials); greater than 85 kg, 520 mg (4 vials)), followed by a single 90 mg subcutaneous injection at Week 8. In participants who demonstrate allergic reaction to the first dose, the second dose can also be administered as IV infusion with pre-infusion desensitization instead of a subcutaneous injection as it allows better control on the rate of drug administration. Participants will continue in the study for a total of 28 weeks and will be able to receive standard of care after the first 16 weeks.
Outcome Measures: For each cohort, the primary outcome is the number of participants who experience treatment response by Week 16. Secondary outcomes for each cohort include changes in visual acuity, the number of participants who experience a recurrence, the number of days to recurrence, presence or extent of macular edema, the amount of retino-vascular leakage, changes in retinal thickening, the length of time to quiescence and the ability to taper concomitant immunosuppressive medications. Safety outcomes for each cohort include the number and severity of systemic and ocular toxicities and adverse events, the proportion of participants who experience vision loss of greater than or equal to 15 letters as measured by Electronic Visual Acuity (EVA) and the number of participants who experience a substantial rise in elevated intraocular pressure (IOP).
-INCLUSION CRITERIA:
Participant has the ability to understand and sign the informed consent document.
Participant is 18 years of age or older.
Participant has negative purified protein derivative (PPD) or quantiferon testing done within three months prior to enrollment or had latent tuberculosis (TB) but has completed prophylactic anti-TB treatment.
Participant has active intermediate uveitis, posterior uveitis or panuveitis in at least one eye requiring systemic therapy. Active disease is defined as:
Participant has visual acuity in at least one eye of 20/400 or better.
Participant is willing and able to comply with the study procedures.
Female participants of childbearing potential must not be pregnant or breast-feeding, have a negative pregnancy test at screening and must be willing to undergo pregnancy testing throughout the study.
Both female participants of childbearing potential and male participants able to father a child must have (or have a partner who has) had a hysterectomy or vasectomy, be completely abstinent from intercourse or must agree to practice two effective methods of contraception throughout the course of the study and for six weeks after the last investigational product injection. Acceptable methods of contraception for this study include:
EXCLUSION CRITERIA: