In a randomized, double-masked, placebo-controlled Phase 2 proof-of-concept study of 17 patients with neuropathic corneal pain (NCP), 75% of per-protocol participants receiving 0.05% urcosimod achieved greater than 80% reduction in pain on a visual analog scale after 12 weeks. The single-center trial at Tufts Medical Center was closed early—17 of a planned 48 patients completed—allowing for an early unmasking of results and leaving the efficacy signal based on a small, per-protocol population rather than an intent-to-treat analysis.
On the back of that signal, OKYO plans to advance urcosimod (formerly OK-101) into a multiple-ascending-dose, randomized, double-masked, placebo-controlled trial enrolling approximately 100 NCP patients across several U.S. sites. The study aims to identify an optimal registration dose, generate multicenter evidence suitable for Phase 3 planning, and further characterize the drug’s micellar formulation attributes. Site negotiations are underway, with topline data targeted for 2026. In parallel, the company is seeking an FDA meeting to define the primary endpoint and requirements for an approvable NCP program; urcosimod holds Fast Track designation, which should support accelerated agency interactions.
Strategically, this is an aggressive attempt to convert a compelling but constrained single-site signal into a registrational path in an indication with no approved therapies and heavy off-label use. The early unmasking underscores both the urgency to establish a clear development trajectory and the risk that the observed effect size may not hold under multicenter conditions and more rigorous analyses. Positioning the next study as a dose-finding bridge to Phase 3 is a practical choice given uncertainty around dose response and the need to pressure-test the 0.05% concentration in a broader, more variable NCP population. The company’s prior multi-center Phase 2 readout in dry eye disease, where multiple endpoints reached statistical significance, provides additional clinical context on safety and ocular pharmacology, though analgesic endpoints in NCP will face distinct evidentiary and regulatory scrutiny.
For sites, the program will hinge on consistent case definition and phenotyping of NCP, standardization of prior-therapy washouts, and disciplined execution of frequent pain assessments. Expect concentration at specialized ophthalmic centers with experience managing chronic corneal pain and established workflows for patient-reported outcomes. CROs and tech vendors should anticipate heavy emphasis on ePRO compliance, data quality controls to mitigate placebo drift in pain scales, and masking rigor amid multi-dose comparisons. Sponsors and investigators will need to manage recruitment in a heterogeneous, underdiagnosed population where background off-label regimens can confound baseline stability and signal detection. For regulators, this trial could frame precedent around acceptable primary endpoints and responder definitions in NCP, including thresholds for clinically meaningful pain reduction and durability at 12 weeks or beyond.
Key near-term watch items are the FDA’s guidance on primary endpoint selection and responder criteria, the final MAD protocol including arm structure, stratification, and statistical hierarchy, and the operational plan for multicenter consistency in pain measurement. Durability of response, dose-response clarity, and reproducibility of the magnitude seen at Tufts will be critical de-risking milestones. Operational risks include placebo response inflation, site-to-site variability, and potential enrollment friction tied to diagnostic ambiguity. If the 2026 MAD readout confirms a robust, durable signal with a clear dose, the Phase 3 path could move quickly under Fast Track. Execution will also depend on CMC readiness for the micellar formulation and the build-out of a site network capable of sustained NCP enrollment at scale.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
