A Phase 3 Randomized Study Comparing the Efficacy of Vorolanib to Aflibercept in Participants with Diabetic Macular Edema

The primary objective of this study is to evaluate the efficacy of EYP-1901, a tyrosine kinase inhibitor, administered as 2686 μg intravitreal (IVT) inserts, compared to aflibercept, in terms of changes in best corrected visual acuity (BCVA) in participants with diabetic macular edema (DME). 5

Secondary objectives include the assessment of:

• efficacy regarding injection burden;
• changes in retinal thickness;
• additional BCVA outcomes;
• the requirement for supplemental injection treatment following administration;
• DME progression.

This clinical trial involves 180 participants diagnosed with diabetic macular edema. The study population consists of both male and female individuals aged 18 years or older. Eligible participants must have a diagnosis of diabetes mellitus, categorized as Type 1 or Type 2, which has remained stable for at least 3 months through the use of insulin or oral antihyperglycemic agents. A requirement for inclusion is a hemoglobin A1c level of less than 10% at the screening visit. Additionally, participants must have a documented history of macular edema associated with diabetic retinopathy. Women of childbearing potential, or men with female partners of childbearing potential, are required to utilize appropriate contraception for the duration of the study.

This Phase 3, multicenter, prospective, randomized, double-masked, parallel-group study is designed to evaluate the efficacy of EYP-1901, a tyrosine kinase inhibitor, compared to aflibercept in participants with diabetic macular edema. The research methodology involves the administration of a 2686 µg intravitreal insert of EYP-1901 or 2 mg of aflibercept. The primary objective is to assess changes in best corrected visual acuity over a 56-week period. Secondary endpoints include the frequency of required injections, changes in retinal thickness, and the rate of improvement in the medical condition. The study sequence begins with a screening visit to verify eligibility, including requirements for diabetes mellitus stability and hemoglobin A1c levels. Following administration, participants undergo scheduled assessments to monitor clinical outcomes. The total duration of treatment evaluation is 56 weeks, with additional monitoring of aflibercept injection requirements up to 88 weeks.

The investigational product is vorolanib, an experimental tyrosine kinase inhibitor (TKI). It is administered as an implant via intravitreal injection at a dose of 2686 µg.

The comparator treatment consists of aflibercept, provided as a solution for injection in a pre-filled syringe. This substance is administered via intravitreal use at a dose of 2 mg to participants with diabetic macular edema (DME).

The primary efficacy endpoint is the change in best corrected visual acuity (BCVA) compared to aflibercept over a 56-week period. Secondary endpoints include the frequency of required injections during the 56-week treatment period and changes in retinal thickness from the initial treatment. Additional assessments involve the percentage of participants who maintain, gain, or lose a specific number of letters on an eye chart over time. Evaluation of the clinical response also includes the percentage of participants requiring supplemental aflibercept injections up to Week 88 and the total number of additional injections required by that timepoint. Furthermore, the study will assess the percentage and rate of improvement in diabetic macular edema (DME) over time.