The number of clinical trials continues to grow for uveitic disease. This review will focus on the phase 2-4 uveitis trials listed as “active” on clinicaltrials.gov, with the majority assessing noninfectious uveitis. Trials listed here have used systemic, topical, and intravitreal administrations of drugs to quell inflammation. This serves as an update to “Current Clinical Trials in Uveitis,” published in June 2023.  

Phase 2 Uveitis Trials

Multicenter Study on the Efficacy and Safety of OCS-01 in Subjects With Uveitis-related and Postsurgical Macular Edema (LEOPARD) (NCT 05608837) is a randomized, parallel assignment, double-masked trial that will assess a new steroid drop, OCS-01, at high dose (6 drops) and low dose (3 drops). The primary endpoint will be changes in central subfield thickness and visual acuity at week 12. 

Phase 2b Pivotal Study of Izokibep in Non-infectious, Intermediate-, Posterior- or Panuveitis (NCT 05384249), sponsored by Acelyrin Inc, is a phase 2b interventional study of an estimated 100 patients to be randomized to 2 arms: placebo subcutaneous treatment administered weekly or izokibep administered subcutaneously weekly. The study will assess izokibep, a blocker of interleukin-17A, an integral player in the inflammatory cascade. The primary outcome will measure the time to treatment failure, which is defined in the study protocol. The study was initiated in 2022 with plans for completion by 2024. 

Intravitreal Adalimumab vs Subcutaneous Adalimumab in Noninfectious Uveitis (IVAS) (NCT 02706704), sponsored by the American University of Beirut Medical Center, is a randomized, parallel assignment, phase 2 trial, comparing intravitreal adalimumab (1.5 mg/0.03 mL) administered at day 0, 2 weeks, and then every 4 weeks, with a subcutaneous injection of adalimumab (40 mg) administered every 2 weeks. The primary outcome measure will be changes in vitreous haze and anterior chamber cell, with secondary outcome measures including visual acuity, macular edema, changes in fluorescein angiography, and ability to taper steroids. 

Minocycline for Chronic Autoimmune Uveitis (NCT05474729) is an interventional phase 2 study with an estimated enrollment of 10 participants at Sun Yat-Sen University. Patients will take oral minocycline (100 mg) daily, with the goal of assessing changes in macular sensitivity, best-corrected visual acuity (BCVA), visual fields, and electroretinogram fluctuations at 6 and 12 months. The study was initiated in 2021 with plans for completion by 2026. 

Comparison of the Efficacy and Safety of Adalimumab of Tocilizumab in Severe Uveitis of Behçet Disease (NCT05874505) is a prospective, randomized, parallel assignment phase 2 study assessing adalimumab (80 mg on day 0, then 40 mg administered every other week, until week 15) vs tocilizumab (162 mg, administered weekly for 15 weeks). The primary endpoint will be the proportion of patients with complete remission of ocular involvement. 

A Study of Brepocitinib in Adults with Active Noninfectious, Nonanterior Uveitis (NEPTUNE) (NCT05523765) is sponsored by Priovant Therapeutics, Inc. This is a randomized, parallel assignment, triple-masked, phase 2 study evaluating the efficacy of oral brepocitibib, dosed at 2 different levels in active intermediate, posterior, and panuveitis. The primary outcome will be the incidence of treatment-emergent adverse events and serious adverse events. 

POC Study to Evaluate the Efficacy and Safety of ESK-001 in Patients With Active Intermediate, Posterior, or Pan Noninfectious Uveitis (OPTYK-1) (NCT05953688), sponsored by Alumis Inc, is a randomized, parallel assignment, quadruple-masked phase 2 study. This study will evaluate the administraton of ESK-001 at two different doses in patients with various types of uveitis, with the primary outcome to compare the efficacy between the 2 dosage groups by week 24.

The Effectivity of Anti Tuberculosis Therapy in Idiopathic Uveitis With Positive Interferon Gamma Release Assay (IGRA): A Randomized Clinical Trial (NCT05005637), sponsored by Fakultas Kedokteran University, is a tripled-masked, phase 2 study assessing 80 participants randomized to either antituberculosis therapy or oral steroid for patients with uveitis with a positive IGRA test. The primary outcome measurement will be percentage of treatment failure, defined as more than 0.5+ anterior-chamber cell or vitreous haze, active retinal or choroidal lesions, or the inability to taper down to less than 7.5 mg of oral prednisone or 2 drops of prednisolone acetate 1% daily. The study enrollment is by invitation only. 

Abatacept in Patients With Birdshot HLA A29 Uveitis (HLA-A29) (NCT03871361), sponsored by the Ziekehuizen Leuven University, is a phase 2 prospective, open-label interventional, proof-of-concept study assessing abatacept administered on a once a week basis with a known diagnosis of birdshot chorioretinopathy. The goal number of participants will be 15. The primary outcome will be time to recurrence in at least 1 eye, established by a worsening of BCVA by at least 15 letters, a 30% increase in central retinal thickness, a 2-step increase in vitreous haze, or new inflammatory lesions in the choroid or retinal vascular changes. The study is listed as completed with results pending.  

Adalimumab Plus Methotrexate for the Treatment of Pediatric Uveitis (NCT04588818), sponsored by Sun Yat-Sen University, is a phase 2, single-group study with a goal number of 30 participants to assess the effects of adalimumab and methotrexate in the treatment of noninfectious panuveitis in children. The primary outcome will be time to remission.  

Reduction or Discontinuation of TNF-α Inhibitor in Noninfectious Uveitis Patients (NCT05155592) is a phase 2, nonmasked, interventional, single-group study at the Sun Yat-Sen University, which will assess the outcomes of tapering off adalimumab in patients with uveitis that was previously controlled with the drug. The study aims to enroll 28 patients and will first administer the drug on a monthly basis (as it was initially administered every 2 weeks for disease control), and if the disease remains quiescent, the administration will stop at 6 months. The primary endpoint will be the relapse rate of inflammation. 

Phase 3 Uveitis Trials

Vamikibart in Participants with Uveitic Macular Edema (Sandcat) (NCT05642325) is a phase 3, multicenter, randomized, double-masked, sham-controlled study to investigate the efficacy and safety profile of intravitreal vamikibart, a humanized IL-6 antibody, in patients with uveitic macular edema. The trial consists of 3 arms. The primary endpoint will measure the prorportion of patients with >15-letter improvement from baseline in visual acuity by week 16. 

A Study to Investigate Vamikibart in Participants with Uveitic Macular Edema (Meerkat) (NCT05642312) has the same basic design as Sandcat. 

Systemic and Topical Antivirals for Control of Cytomegalovirus Anterior Uveitis: Treatment Outcomes (STACCATO) (NCT03586284), sponsored by the University of California, San Francisco, is a double-masked, randomized trial comparing oral valgancyclovir, topical gancyclovir (2%), and placebo for cytomegalovirus anterior uveitis. Ninety-nine participants are estimated to be enrolled. The primary outcome measured is change in viral load from day 0 to day 28. The study was started in March of 2020 with plans to end the trial by March 2025. 

The Use of 2 Yutiq vs Sham for Treatment of Chronic Noninfectious Intraocular Inflammation Affecting the Posterior Segment (TYNI) (NCT05486468) is sponsored by Texas Retina Associates and Alimera Sciences. This is a phase 3, prospective, randomized, double-masked collaborative study in 30 participants assessing patients who undergo 2 FAI (Yutiq) implants on day 1 vs those who receive 2 sham injections on day 1. The primary outcome measurement will be the recurrence of uveitis at month 6. The study was initiated in October 2002 with estimated completion in December 2024. 

A Study of Brepocitinib in Adults with Active, Noninfectious, Nonanterior Uveitis (CLARITY) (NCT06431373) is a phase 3 study assessing brepocitinib. The primary endpoint will be the proportion of patients meeting treatment failure criteria on or after week 6, up to week 24. 

Adalimumab vs Conventional Immunosuppression for Uveitis Trial (ADVISE) (NCT03828019), sponsored by JHSPH Center for Clinical Trials, is a phase 3, randomized, open-label trial of an estimated 222 participants, comparing adalimumab to conventional immunosuppression (including azathioprine, methotrexate, mycophenolate, cyclosporine, and tacrolimus). The primary outcome will be obtaining corticosteroid-sparing success (7.5 mg of daily corticosteroid or below) for 2 consecutive visits within the first 6 months. The study was initiated in September 2019 with plans for termination by September 2024.  

A Study of Baricitinib (LY3009104)in Participants From 2 Years to Less Than 18 Years Old With Active JIA-associated Uveitis or Chronic Anterior Antinuclear Antibody-positive Uveitis (NCT04088409),  sponsored by Eli Lilly and Company, is a phase 3, randomized, nonmasked trial assessing baricitinib vs adalimumab in 40 pediatric participants with active juvenile idiopathic arthritis (JIA)–associated uveitis or chronic anterior antinuclear antibody-positive associated uveitis. The primary outcome will measure the percentage of responders, which is defined as a 2-step decrease in inflammation.   

Efficacy, Safety, and Costs of Methotrexate, Adalimumab, or Their Combination in Noninfectious Nonanterior Uveitis (Co-THEIA) (NCT04798755), sponsored by San Carlos Hospital, is a phase 3, randomized, single-masked study assessing 3 arms: (1) adalimumab, (2) methotrexate, and (3) adalimumab and methotrexate for nonanterior, noninfectious uveitis. The study aims to include 192 participants. The primary outcome will measure clinical response, defined as complete resolution of inflammation by week 16 and maintained until week 52. The study began in January 2022 with an estimated completion date of October 2025. 

Preventing Extension of Oligoarticular Juvenile Idiopathic Arthritis (Limit-JIA) (NCT03841357) is an open-label, phase 3, parallel assignment, nonmasked study assessing the efficacy of subcutaneous abatacept (Orencia) in preventing the extension of JIA. The study was initiated in October 2019 with plans to conclude by December 2023. The study has 2 parts, with part 1 discontinued in February 2022. Part 2 is a nonrandomized continuation assessing the administration of abatacept vs the usual care of JIA, in patients with limited JIA to see if the medication can prevent extension of the disease or uveitis. The completion of the study is estimated for early 2025. 

A Study of TRS01 in Subjects With Active Noninfectious Anterior Uveitis Including Subjects With Uveitic Glaucoma (NCT05042609) organized by Tarsier, is a phase 3, randomized, quadruple-masked assessment of a drop, TRS01, compared to FDA-approved steroid drops in the treatment of active, noninfectious, anterior uveitis. The study has 162 participants and is no longer actively recruiting. The primary outcome measured will be the amount of anterior chamber cell.  

Phase 4 Uveitis Trials

Ixekizumab for the Management of Refractory Noninfectious Uveitis: A Proof of Concept Study (NCT06085079) is a randomized, parallel assignment, phase 4 study. It aims to explore the efficiacy of ixekizumab, a humanized monoclonal antibody that acts on interleukin 17A in patients with intermediate, posterior, panuveitis or chronic-steroid dependent anterior uveitis who have failed other forms of immunosuppression. The study will aim to enroll 20 participants with 2 arms. One arm will received the drug every 2 weeks, while the other will receive the drug every 4 weeks. The primary endpoint will be a composite endpoint of vision, inflammatory control, medication tapering, and cystoid macular edema at week 10. 

Fluocinolone Acetonide Intravitreal Implant 0.18 mg in the Treatment of Chronic Noninfectious Posterior Segment Uveitis (NCT05322070), sponsored by Alimera Sciences, is a phase 4, prospective, open-label, study assessing the 2-year outcomes of the flucinolone acetonide intravitreal implant (Yutiq). There are an estimated 125 participants. The primary outcomes will include BCVA change as well as CST change. The study was initiated in June of 2022, with expected completion in November 2024. 

Adalimumab in JIA-associated Uveitis Stopping Trial (ADJUST) (NCT 03816397), sponsored by the University of California, San Francisco, is a phase 3, randomized, quadruple-masked trial of an estimated 118 participants with either JIA associated uveitis or chronic, ANA-positive anterior uveitis comparing the continuation of adalimumab vs the discontinuation of the drug (with placebo administered). The primary outcome will be time to treatment failure, with an estimated study completion date of July 2025. 

Ozurdex Monotherapy Trial (OM) (NCT05101928),  sponsored by Ottawa Hospital Research Institute, is a randomized, parallel assignment, triple-masked study of 84 participants to assess the treatment of Ozurdex (AbbVie) for noninfectious intermediate, posterior, or panuveitis. Patients will be treated with intravitreal Ozurdex or an oral prednisone taper. The primary endpoint will measure the percentage of patients with a vitreous haze score of 0 at the 6-month mark. The completion date of the study is set for September 2027. 

Biologic Therapy in Pediatric JIA Uveitis (NCT05540743), sponsored by Kasr El Aini Hospital, aims to assess in 250 participants, through an open-label study, the efficacy of anti-TNR alpha agents in pediatric patients with JIA, specifically in the Egyptian population. The study is no longer recruiting. The primary outcome will focus on the steroid-sparing effects of the medication by 24 months, with estimated study completion by April 2024.  

A Study to Assess Change in Disease Activity and Adverse Events of Adalimumab in Chinese Participants Requiring High-dose Corticosteroids for Active Noninfectious Intermediate, Posterior, or Panuveitis (NCT05414201) is an AbbVie-sponsored, Chinese-based, phase 4, nonmasked, single-group assignment study with a target group of 87 participants who will receive adalimumab for either intermediate, posterior, or panuveitis. The primary outcome will measure the percentage of patients who obtain disease quiescence in both eyes. The study is recruiting and aims to finish by June 2024. 

Topical 2% Ganciclovir Eye Drop for CMV Anterior Uveitis/Endotheliitis (NCT02943057) is sponsored by Singapore National Eye Centre. This open-label study will assess the treatment response of 2% guttae ganciclovir in 25 patients who are diagnosed with cytomegalovirus (CMV) anterior-segment infection. After 6 weeks, an aqueous chamber paracentesis will be done to test for viral load as well as ganciclovir drug levels. The primary outcome will be the median concentration of ganciclovir in aqueous by HPLC-mass spectrometry. RP

Sruthi Arepalli, MD, is an assistant professor in the vitreoretinal and uveitis service at Emory University in Atlanta, Georgia. She reports consultancy to EyePoint Pharmaceuticals. Reach her at sruthiarepalli@gmail.com.