Ustekinumab for Active Sight-Threatening Uveitis

Phase 1

Withdrawn

• Conditions: Uveitis

• Registration Number: NCT01647152
• Lead Sponsor: National Eye Institute (NEI)

Brief Summary

Background:

- Uveitis is an eye inflammation that can cause vision loss. It is treated with eye drops, drugs and sometimes surgery. In some people, treatment may not prevent vision loss. A type of white blood cells called T-cells often have a role in causing uveitis. In some cases of uveitis, T-cells attack the eye and cause inflammation. A drug called ustekinumab reduces inflammation from these T-cells. Researchers want to see if ustekinumab can be used to treat uveitis.

Objectives:

- To see if ustekinumab can be used to treat uveitis.

Eligibility:

- Individuals at least 18 years of age who have active uveitis that needs treatment.

Design:

* Participants will be screened with a physical exam, eye exam, and medical history. Blood and urine samples will be taken.

* Participants will have at least eight clinic visits during the 64-week study period. After the first visit, visits will occur at 2, 4, and 8 weeks, and then every 12 weeks.

* Participants will have a ustekinumab injection at the first study visit. They will have additional doses at the second and third visits, and then every 12 weeks until 1 year after the first dose (Week 52).

* Treatment will be monitored with frequent blood tests and eye exams. Other standard treatments for uveitis may be given as needed.

* There will be a final study visit 3 months after the last injection.

Detailed Description

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 subcutaneous injections of ustekinumab as a possible treatment for active intermediate uveitis, posterior uveitis or panuveitis.

Study Population: Five participants with active intermediate uveitis, posterior uveitis or panuveitis who meet the inclusion criteria will be initially enrolled. Up to seven participants may be enrolled, as up to two participants may be accrued to account for participants who withdraw from the study prior to Week 8.

Design: This is a prospective, non-randomized, uncontrolled, single-center pilot study to evaluate subcutaneous injections of ustekinumab as a possible treatment for active intermediate uveitis, posterior uveitis or panuveitis. Participants will receive a 90 mg subcutaneous injection of ustekinumab at baseline and a second and third injection at Week 2 and 4 and every 12 weeks thereafter. Participants will continue to receive injections of ustekinumab every 12 weeks until Week 52. Participants will return for a final safety visit 12 weeks later.

Outcome Measures: The primary outcome is the number of participants who experience treatment response (as defined in Appendix 1) by Week 8. Secondary outcomes 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 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 Early Treatment Diabetic Retinopathy Study (ETDRS) letters and the number of participants who experience a substantial rise in elevated intraocular pressure (IOP).

Study Timeline

• Study Start: 2012-07-03
• Study First Submitted: 2012-07-19
• Study First Submitted QC: 2012-07-19
• Study First Posted: 2012-07-20
• Status Verified: 2014-09-05
• Primary Completion: 2015-06-30
• Study Completion: 2015-06-30
• Last Update Submitted: 2019-12-04
• Last Update Posted: 2019-12-05

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
The primary outcome is the number of participants who experience at least a 2-step (or down to grade 0) reduction in inflammation as per the Standardization of Uveitis Nomenclature (SUN) criteria by Week 8.