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Uveitis Now: Latest Advancements and Clinical Trials

Saitiel Sandoval Gonzalez

Saitiel Sandoval Gonzalez

Edmund Tsui, MD

Edmund Tsui, MD

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Discover the latest advancements in uveitis research with clinical trial updates to keep ophthalmologists up to date on biopharmaceutical innovations.

Uveitis Now: Latest Advancements and Clinical Trials
Uveitis, a complex condition characterized by ocular inflammation, can be challenging to treat and may result in severe consequences. It is estimated that uveitis accounts for 10 to 15% of all cases of blindness in economically developed countries.1
In recent years, advancements in medical research have led to promising developments in treating uveitis. Clinical trials exploring novel therapeutic approaches aim to address the unmet medical needs of uveitis patients.
This article delves into the current landscape of ongoing and recently completed clinical trials for uveitis, examining the latest interventions and their potential to revolutionize the management of this sight-threatening condition. The data summarized below are available via ClinicalTrials.gov and news releases.

Overview of phase 2 uveitis clinical trials

Phase 2 clinical trials aim to evaluate the efficacy of an intervention and further study its safety. The following uveitis clinical trials are currently in phase 2.

Pivotal study of Izokibep in uveitis

Pivotal Study of Izokibep in Non-infectious, Intermediate-, Posterior- or Pan-Uveitis is a phase 2b/3 study sponsored by the biopharmaceutical company Acelyrin.2 This clinical trial aims to study the efficacy and safety of Izokibep, an interleukin-17A (IL-17A) inhibitor, in the aforementioned uveitic conditions.
IL-17A plays a vital role in the inflammatory cascade of non-infectious uveitis and has previously been targeted by other inhibitors. In this trial, subcutaneous Izokibep is being compared against a subcutaneous placebo.
This study is still recruiting participants and is estimated to conclude in late 2024.

Brepocitinib in adults with active non-infectious non-anterior uveitis (NEPTUNE)

A Study of Brepocitinib in Adults With Active Non-Infectious Non-Anterior Uveitis (NEPTUNE) is a phase 2 trial sponsored by Priovant Therapeutics.3 Here, they aim to evaluate the safety and efficacy of brepocitinib in adults with non-infectious intermediate, posterior, or pan-uveitis.
Brepocitinib is a Janus kinase (JAK) inhibitor with selectivity for tyrosine kinase 2 (TYK2) and JAK1. Like other JAK inhibitors, brepocitinib reduces the inflammatory cytokine production in active uveitis.
This study primarily measures adverse event outcomes between two doses of oral brepocitinib. While the study has stopped recruitment, it remains active and is estimated to conclude in mid-2024.

ESK-001 for non-infectious uveitis (OPTYK-1)

POC Study to Evaluate the Efficacy and Safety of ESK-001 in Patients With Active Intermediate, Posterior, or Pan NIU (OPTYK-1) is yet another phase 2 clinical trial involving subjects with uveitis.4 This study, sponsored by Alumis, aims to examine the safety and efficacy of ESK-001, another highly selective TYK2 inhibitor.
This trial also contains two study arms with two different ESK-001 dosing levels. This study is still active and recruiting participants, with an estimated end date in 2025.

A look at phase 3 uveitis clinical trials

Phase 3 clinical trials usually aim to evaluate the effectiveness of a treatment or intervention in comparison to existing therapy standards. The following uveitis clinical trials are currently in phase 3.

TRS4Vision for non-infectious anterior uveitis

A Study of TRS01 in Subjects With Active Non-infectious Anterior Uveitis Including Subjects With Uveitic Glaucoma (also known as TRS4Vision) was a phase 3 clinical trial sponsored by Tarsier Pharma that concluded in June 2023.5 It aimed to investigate the efficacy and safety of TRS01, or dazdotuftide, in drop form against a standard treatment of steroid drops.
Dazdotuftide is a new chemical entity (NCE) that inhibits important inflammatory modulators such as neuropilin 1 (NRP1), toll-like receptors (TLRs), and angiotensin-converting enzyme 2 (ACE-2). The study's primary outcome was not met; however, the company states that the results showed a promising mix of efficacy and safety.
They gained approval from the FDA in January 2024 under a Special Protocol Assessment (SPA) to begin the Tarsier-04 Phase 3 clinical trial.6 This new trial’s endpoints are ones that achieved a p-value less than 0.01 in the previous TRS4Vision trial.

Vamikibart in patients with uveitic macular edema (Meerkat/Sandcat)

Study to Investigate Vamikibart in Participants With Uveitic Macular Edema (Meerkat/Sandcat) are a pair of clinical studies sponsored by Genentech that aim to assess the safety and efficacy of vamikibart in participants with uveitic macular edema.7,8
Vamikibart is a monoclonal antibody targeting IL-6 to decrease ocular inflammation. Participants in this study will receive either one of two doses of intravitreal vamikibart injections or a sham intravitreal injection.
Meerkat and Sandcat are active and recruiting patients and are estimated to conclude in mid-2025.

Adalimumab vs. conventional immunosuppression for uveitis (ADVISE)

Adalimumab vs. Conventional Immunosuppression for Uveitis Trial (ADVISE) is a phase 3 clinical trial sponsored by the Johns Hopkins School of Public Health (JHSPH) and the National Institute of Health (NIH).9
This study compares the biologic adalimumab against conventional immunosuppressive agents such as methotrexate, cyclosporine, and cyclophosphamide in treating uveitis.
Adalimumab is a monoclonal antibody against tumor necrosis factor-alpha (TNF-α), previously implicated in uveitic inflammation. The study's primary aim is to analyze adalimumab’s ability to taper participants to a low dose of corticosteroid treatment within 6 months compared to other forms of conventional immunosuppression.
This study remains active and is estimated to conclude in the last quarter of 2024.

Macular edema ranibizumab vs. intravitreal anti-inflammatory therapy (MERIT)

Macular Edema, Ranibizumab vs. Intravitreal Anti-inflammatory Therapy Trial (MERIT), was another phase 3 clinical trial sponsored by JHSPH and the NIH.10
This study compared intravitreal ranibizumab, intravitreal methotrexate, and intravitreal dexamethasone implant in a 12-week parallel design. Ranibizumab is a monoclonal antibody fragment that inhibits vascular endothelial growth factor A (VEGF-A).
After the study, intravitreal dexamethasone was shown to significantly reduce retinal thickness from baseline and to be the only intervention to significantly improve best-corrected visual acuity (BCVA).
The researchers concluded that intravitreal steroid treatment remains the preferred therapy for uveitis-associated macular edema, but ranibizumab may be considered if there are serious contraindications to corticosteroid treatment.

Phase 4 new uveitis therapies

Phase 4 clinical trials evaluate new drugs or therapies' long-term benefits and side effects.
Adalimumab in JIA-associated Uveitis Stopping Trial (ADJUST) is a phase 4 clinical trial funded by the NIH.11 Adalimumab, a TNF-α inhibitor, is effective for juvenile idiopathic arthritis (JIA) associated uveitis and chronic anterior uveitis.
This study aims to determine if adalimumab can be safely terminated in participants with long-term adalimumab use. The researchers will analyze the time to treatment failure between subcutaneous adalimumab and subcutaneous placebo treatments.
ADJUST has stopped enrolling after 118 participants but remains active, with an estimated completion in mid-2025.

Table of phase 2b to 4 clinical trials in uveitis

Table 1 lists the names and phases of phase 2b to phase 4 clinical trials in uveitis. *Estimated completion date as listed on ClinicalTrials.gov.
Trial NamePhaseSponsorInterventionEstimated Completion Date*ClinicalTrials.gov Identifier
Phase 2b Pivotal Study of Izokibep in Non-infectious, Intermediate-, Posterior- or Pan-uveitis2bAcelyrinIzokibep10/2024NCT05384249
Neptune2PrintBrepocitinib07/2024NCT05523765
OPTYK-12AlumisESK-10004/2025NCT05953688
Tarsier-043Tarsier PharmaDazdotuftideTBDTBD
Meerkat/Sandcat3Genentech/Hoffmann-La RocheVamikibart06/2025NCT05642312/NCT05642325
ADVISE3JHSPH/NIHAdalimumab09/2024NCT03828019
MERIT3JHSPH/NIHIntravitreal ranibizumab, intravitreal methotrexate, intravitreal dexamethasone implant02/2022NCT02623426
ADJUST4NIHAdalimumab07/2025NCT03816397
Table 1: Courtesy of the authors.

Conclusions

The landscape of clinical trials for uveitis presents a hopeful outlook for patients grappling with this challenging condition.
From innovative biologics targeting specific inflammatory pathways to repurposed drugs and novel interventions, researchers are working to improve treatment outcomes and quality of life for individuals affected by uveitis.
  1. Joltikov KA, Lobo-Chan A-M. Epidemiology and risk factors in non-infectious uveitis: A systematic review. Front Med (Lausanne). 2021;8:695904. doi:10.3389/fmed.2021.695904
  2. Phase 2b Pivotal Study of Izokibep in Non-infectious, Intermediate-, Posterior- or Pan-uveitis. Clinicaltrials.gov identifier: NCT05384249. Updated March 04, 2024. Accessed March 15, 2024. https://clinicaltrials.gov/study/NCT05384249.
  3. A Study of Brepocitinib in Adults With Active Non-Infectious Non-Anterior Uveitis (NEPTUNE). Clinicaltrials.gov identifier: NCT05523765. Updated July 19, 2023. Accessed March 15, 2024. https://clinicaltrials.gov/study/NCT05523765.
  4. POC Study to Evaluate the Efficacy and Safety of ESK-001 in Patients With Active Intermediate, Posterior, or Pan NIU (OPTYK-1). Clinicaltrials.gov identifier: NCT05953688. Updated March 01, 2024. Accessed March 15, 2024. https://clinicaltrials.gov/study/NCT05953688.
  5. A Study of TRS01 in Subjects With Active Non-infectious Anterior Uveitis Including Subjects With Uveitic Glaucoma. Clinicaltrials.gov identifier: NCT05042609. Updated August 28, 2023. Accessed March 15, 2024. https://clinicaltrials.gov/study/NCT05042609.
  6. Tarsier Pharma. Tarsier Pharma Receives FDA Agreement Under Special Protocol Assessment (SPA) for Tarsier-04 Phase 3 Trial of TRS01 Ophthalmic Solution for the Treatment of Non-infectious Uveitis including Uveitic Glaucoma. Tarsier Pharma. Published January 16, 2024. Accessed March 15, 2024. https://tarsierpharma.com/2024/01/17/january-16-2024/.
  7. A Study to Investigate Vamikibart in Participants With Uveitic Macular Edema (Meerkat). Clinicaltrials.gov identifier: NCT05642312. Updated March 05, 2024. Accessed March 15, 2024. https://clinicaltrials.gov/study/NCT05642312.
  8. Vamikibart in Participants With Uveitic Macular Edema (Sandcat). Clinicaltrials.gov identifier: NCT05642325. Updated February 28, 2024. Accessed March 15, 2024. https://clinicaltrials.gov/study/NCT05642325.
  9. Adalimumab vs. Conventional Immunosuppression for Uveitis Trial (ADVISE). Clinicaltrials.gov identifier: NCT03828019. Updated November 18, 2023. Accessed March 15, 2024. https://clinicaltrials.gov/study/NCT03828019.
  10. Macular Edema Ranibizumab v. Intravitreal Anti-inflammatory Therapy Trial (MERIT). Clinicaltrials.gov identifier: NCT02623426. Updated July 10, 2023. Accessed March 15, 2024. https://clinicaltrials.gov/study/NCT02623426.
  11. Adalimumab in JIA-associated Uveitis Stopping Trial (ADJUST). Clinicaltrials.gov identifier: NCT03816397. Updated March 07, 2024. Accessed March 15, 2024. https://clinicaltrials.gov/study/NCT03816397.
Saitiel Sandoval Gonzalez
About Saitiel Sandoval Gonzalez

Saitiel Sandoval Gonzalez is a medical student at the UCLA David Geffen School of Medicine. He is passionate about improving eyecare, particularly in medically underserved communities. In his free time, he enjoys hiking, camping, and exploring new places to eat.

More by Saitiel Sandoval Gonzalez
Saitiel Sandoval Gonzalez
Edmund Tsui, MD
About Edmund Tsui, MD

Edmund Tsui, MD, is an Assistant Professor of Ophthalmology at the Stein Eye Institute, David Geffen School of Medicine at the University of California, Los Angeles (UCLA).

He completed his medical training at Dartmouth Medical School followed by an ophthalmology residency at the New York University (NYU) School of Medicine, where he was elected Chief Resident. He went on to complete his fellowship in Uveitis and Ocular Inflammatory Disease at the Francis I. Proctor Foundation at University of California, San Francisco (UCSF).

In addition to caring for patients with uveitis and ocular inflammatory diseases, Dr. Tsui is also committed to advancing the field of ophthalmology. His research focuses on utilizing state of the art ophthalmic imaging technology to improve the diagnosis and monitoring of uveitis.

He is also a co-investigator in the MERIT, ADVISE, and ZEDS multicenter clinical trials investigating therapeutics for uveitis. He is the author of over 70 peer-reviewed publications and has given talks at national and international conferences.

More by Edmund Tsui, MD
Edmund Tsui, MD
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