A Phase IIa Multicenter, Randomized, Vehicle-Controlled, Dose Escalating Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of CBT-001 Ophthalmic Solution in Patients With Primary or Recurrent Pterygium

Abstract

PurposeTo evaluate the safety and efficacy of CBT-001, a multi-target tyrosine kinase inhibitor (MKI) eyedrop, for pterygia. DesignPhase 2 clinical trial. Stage 1 was a single center, open-labeled, vehicle-controlled study. Stage 2 was a multicenter, randomized, double-masked, vehicle-controlled trial. ParticipantsPatients with primary or recurrent pterygia. Main Outcome MeasuresThe primary efficacy endpoint was lesion vascularity based on masked grading of photographs by an independent reading center. Other endpoints included dimensions of pterygia and safety. MethodsIn Stage 1, 24 eyes of 24 patients received one drop of CBT-001 in a dose escalation fashion (0.02%, 0.05%, and 0.2%) to determine the maximally tolerated dose based on adverse events and blood drug levels. In Stage 2, subjects were randomly assigned to receive the maximally tolerated dose of CBT-001 or vehicle dosed three times a day (TID) for 4 weeks with a 20-week follow up. ResultsIn Stage 1, the plasma maximum concentration (Cmax) values for all doses of CBT-001 were at or below the limit of detection (0.01 ng/mL). The most commonly reported adverse events were mild foreign body sensation and irritation. CBT-001 0.2% was evaluated in Stage 2. Baseline demographic characteristics were similar between patients receiving CBT-001 (n = 25) and vehicle (n = 23). After 4 weeks of dosing, mean change from baseline in pterygium vascularity scores was –0.8 ± 0.7 (mean ± standard deviation) in subjects receiving CBT-001 0.2% and 0.0 ± 0.5 in subjects receiving vehicle (P < 0.001; 95% confidence interval [CI]: -1.12, -0.40). Pterygium vascularity scores remained significantly decreased, after the 4-week dosing period, at weeks 8 and 16, but not at week 24. Mean changes from baseline in the length of the pterygia were also significantly lower in subjects receiving CBT-001 compared to vehicle at weeks 2, 4, and 8 (P≤0.014). The most commonly reported adverse events were ocular, mild in severity, resolved after therapy, and did not result in discontinuation. ConclusionsCBT-001 0.2% decreased pterygia vascularity and lesion length after 4 weeks of dosing with a prolonged effect after dosing. The drug was well tolerated with minimal detected systemic drug levels.