Ustekinumab (STELARA) for the Treatment of Active Sight-Threatening Uveitis (STAR Study)
Condition: Uveitis
MeSH terms: Uveitis
Intervention: Ustekinumab; Ustekinumab
Intervention description: Subcutaneous Injection; Intravenous Infusion
Intervention MeSH terms: Ustekinumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 8.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Panuveitis; Intermediate Uveitis; Uveitis

Summary:

      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:

        -  Medical and eye disease history

        -  Physical and eye exams

        -  Blood and urine tests

        -  Fluorescein angiography: A needle guides a thin plastic tube into an arm vein. A dye is
           injected into the tube. The dye travels through the veins up to the blood vessels in the
           eyes. A camera takes pictures of the dye as it flows through the blood vessels in the
           eyes.

        -  Cohort 1 - Ustekinumab injections at Weeks 0, 4, and 8: The injection is under the skin
           of the upper arm, leg, or abdomen.

      Participants will have their uveitis monitored and receive standard uveitis care during the
      study.

        -  Cohort 2 - Ustekinumab injections via intravenous (IV) injection at first visit,
           followed by a single 90 mg injection of ustekinumab under the skin of the upper arm, leg
           or abdomen. For the IV injection a needle will be used to guide a thin plastic tube
           (catheter) into one of the arm veins. The needle will be removed, leaving only the
           catheter in the vein.
    

Eligibility criteria:

        -INCLUSION CRITERIA:

          1. Participant has the ability to understand and sign the informed consent document.

          2. Participant is 18 years of age or older.

          3. 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.

          4. Participant has active intermediate uveitis, posterior uveitis or panuveitis in at
             least one eye requiring systemic therapy. Active disease is defined as:

               -  +1 or more vitreous haze (according to Standardization of Uveitis Nomenclature
                  (SUN) criteria) AND/OR

               -  Active chorioretinitis or leakage on Fluorescein angiography (FA)(that is in more
                  than one quadrant) that requires treatment.

          5. Participant has visual acuity in at least one eye of 20/400 or better.

          6. Participant is willing and able to comply with the study procedures.

          7. 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.

          8. 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:

               -  hormonal contraception (i.e., birth control pills, injected hormones, dermal
                  patch or vaginal ring),

               -  intrauterine device,

               -  barrier methods (diaphragm, condom) with spermicide, or

               -  surgical sterilization (tubal ligation).

        EXCLUSION CRITERIA:

          1. Participant has a significant active infection (an infection requiring treatment as
             determined by the medical team), including active tuberculosis or human
             immunodeficiency virus (HIV).

          2. Participant received a live vaccination within the past six weeks.

          3. Participant is expected to receive a live vaccination at any time during the study.

          4. Participant received the Bacillus Calmette-Guerin (BCG) vaccine within the past year.

          5. Participant is expected to receive the BCG vaccine at any time during the study or up
             to one year after discontinuing ustekinumab.

          6. Participant has a history of cancer (other than a non-melanoma skin cancer) diagnosed
             within the past five years.

          7. Participant has received intraocular (or periocular) steroid or anti-vascular
             endothelial growth factor (VEGF) injections within the last six weeks.

          8. Participant received rituximab within the last six months or another biologic agent
             (e.g., infliximab, daclizumab, adalimumab) within the last two months.

          9. Participant has received alkylating agents (e.g., cyclophosphamide, chlorambucil)
             within the last nine months.

         10. Participant has a known hypersensitivity to ustekinumab or any of its components.