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Ophthalmology · Clinical trials

Uveitis Clinical Trials

Approved therapies, the pivotal-trial endpoints they were judged on, the magnitude of benefit — and the drugs that failed their endpoints, and why.

Indication overview

About uveitis — and why its trials are hard

Non-infectious uveitis is a group of immune-mediated intraocular inflammatory diseases affecting the uveal tract, classified anatomically as anterior, intermediate, posterior or panuveitis. Intermediate and posterior forms threaten sight through macular oedema, vasculitis, retinal damage and secondary glaucoma or cataract, and account for a substantial share of preventable blindness. Corticosteroids, systemic or local, remain first-line, but chronic use carries cataract, glaucoma and systemic toxicity, driving demand for steroid-sparing options. Adalimumab, an anti-TNF-alpha antibody, became the first biologic approved for non-infectious intermediate, posterior and panuveitis (2016) on the strength of the VISUAL-I and VISUAL-II trials, which measured time to treatment failure. Sustained-release corticosteroid implants provide durable local control: the dexamethasone implant (Ozurdex, HURON) for posterior segment inflammation and fluocinolone acetonide implants (Yutiq, Retisert) for chronic disease. Methotrexate, mycophenolate and other immunomodulators are used off-label. Trial endpoints centre on time to treatment failure, control of vitreous haze and inflammatory recurrence, reflecting the relapsing nature of the disease.

Indication
Uveitis
ICD-10-CM
H20.9 — Unspecified iridocyclitis

Approved therapies & pivotal evidence

What's been approved — and by how much it moved the endpoint

Drug (brand)ApprovedSettingPivotal trialPrimary endpointMagnitude of benefit
adalimumab (Humira)2016Non-infectious intermediate, posterior and panuveitisVISUAL-I (active disease) and VISUAL-II (inactive/controlled disease)Time to treatment failure (composite of inflammation, vision and lesions)VISUAL-I: median time to failure 24 vs 13 weeks (HR ~0.50); VISUAL-II: HR ~0.57, both favouring adalimumab
dexamethasone intravitreal implant (Ozurdex)2010Non-infectious posterior segment uveitis (corticosteroid)HURONProportion with vitreous haze score of 0 at week 8~47% reached vitreous haze 0 with the 0.7 mg implant vs ~12% sham
fluocinolone acetonide implant (Yutiq / Retisert)2018Chronic non-infectious posterior uveitis (sustained-release)Yutiq phase 3 (0.18 mg) program; Retisert approved 2005Recurrence of uveitis over 6–12 monthsYutiq roughly halved recurrence vs sham over 12 months (~28% vs ~86% recurrence in pivotal data)

Where trials have failed

Drugs that missed their endpoint — and what contributed

The most instructive lessons in uveitis development come from programmes that failed the endpoint that mattered.

Drug / trialEndpoint outcomeWhat contributed
gevokizumab (anti-IL-1beta) — EYEGUARD-BFailed to meet the primary endpoint (time to first acute ocular exacerbation) in Behçet's disease uveitisNo significant reduction in uveitic flares versus placebo on background therapy; IL-1beta blockade insufficient to control the disease, ending the program
secukinumab (anti-IL-17A) — SHIELD, INSURE and ENDUREIntravenous/subcutaneous secukinumab failed to meet primary endpoints for reducing uveitis recurrence and steroid-sparing in non-infectious uveitisSubcutaneous dosing may have given inadequate exposure; IL-17 blockade did not translate to meaningful control, and the ocular program was discontinued

Choosing the right endpoint

Primary endpoints that matter in uveitis trials

  • Time to treatment failure — Composite regulatory endpoint (VISUAL trials) combining new lesions, vitreous haze, anterior chamber cells and BCVA decline
  • Vitreous haze score — Standardised (NEI/SUN) grading of vitreous opacity; a score of 0 signifies quiescence, used in HURON
  • Uveitis recurrence rate — Frequency of inflammatory relapse over follow-up; primary measure for sustained-release implants
  • Corticosteroid-sparing — Ability to taper systemic steroids while maintaining control; key practical benefit of biologics and implants

How iNGENū runs uveitis trials

Physician-led design, built for FDA submission

Endpoint & biomarker strategy

Board-certified specialists design endpoints and patient selection aligned to current FDA guidance for this indication.

FDA-ready data

Built to ICH-GCP and 21 CFR 312.120, with direct FDA submission — data accepted by the FDA, EMA and MHRA.

Faster, lower-cost delivery

~4-week ethics via the TGA CTN scheme, up to 43.5% R&D rebate, and 80–90% below US CRO cost.

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Frequently asked questions

Uveitis clinical trials — FAQs

Why is adalimumab important in uveitis management?
Adalimumab was the first biologic approved for non-infectious intermediate, posterior and panuveitis; the VISUAL-I and VISUAL-II trials showed it significantly prolonged time to treatment failure, providing a steroid-sparing option for chronic disease.
When are corticosteroid implants used?
Sustained-release implants such as dexamethasone (Ozurdex) and fluocinolone (Yutiq, Retisert) deliver durable local control for posterior segment inflammation, useful for unilateral or refractory disease, but they raise the risk of cataract and glaucoma.
Why have several biologics failed in uveitis?
Agents such as gevokizumab (IL-1beta) and secukinumab (IL-17A) missed primary endpoints, suggesting these specific cytokine pathways are insufficient to control uveitic inflammation, whereas TNF-alpha blockade with adalimumab proved effective.

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