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

Purpose: To evaluate the safety and efficacy of CBT-001, a multitarget tyrosine kinase inhibitor eyedrop, for pterygia.

Design: Phase II clinical trial. Stage 1 was a single center, open-labeled, vehicle-controlled study. Stage 2 was a multicenter, randomized, double-masked, vehicle-controlled trial.

Participants: Patients with primary or recurrent pterygia.

Main outcome measures: The primary efficacy end point was lesion vascularity based on masked grading of photographs by an independent reading center. Other end points included dimensions of pterygia and safety.

Methods: In stage 1, 24 eyes of 24 patients received 1 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 (AEs) and blood drug levels. In stage 2, subjects were randomly assigned to receive the maximally tolerated dose of CBT-001 or vehicle dosed 3 times a day for 4 weeks with a 20-week follow-up.

Results: In stage 1, the plasma maximum concentration values for all doses of CBT-001 were at or below the limit of detection (0.01 ng/ml). The most commonly reported AEs 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, the 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: -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. The mean changes from baseline in the length of the pterygia were also significantly lower in subjects receiving CBT-001 compared with vehicle at weeks 2, 4, and 8 (P ≤ 0.014). The most commonly reported AEs were ocular, mild in severity, resolved after therapy, and did not result in discontinuation.

Conclusions: CBT-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.

Financial disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Keywords: Angiogenesis; Cornea; Pterygium; Tyrosine kinase inhibitor; Vascular endothelial growth factor.

Figure 1

Study design. DRC = Data Review Committe; PK = pharmakokinetics; TID = 3 times a day.

Figure 3

The mean change from baseline in pterygium vascularity intensity at each scheduled visit. The 95% confidence interval: week 2: −0.95, −0.49; week 4: −1.12, −0.40; week 8: −0.70, −0.13; week 16: −0.87, −0.30; week 24: −0.50, 0.08.

Figure 4

A representative eye treated with CBT-001 0.2%. The left panel depicts the eye at day 1. The right panel shows reduced pterygia vascularity at week 4.

Figure 5

The mean change from baseline in corneal pterygium lesion length (mm) at each scheduled visit. The 95% confidence interval: week 2: −0.39, −0.07; week 4: −047, −0.08; week 8: −0.44, −0.05; week 16: −0.25, −0.08; week 24: −0.12, 0.16.

Figure 6

The mean change from baseline in conjunctival hyperemia intensity at each scheduled visit. The 95% confidence interval: week 2: −0.72, −0.19; week 4: −1.12, −0.48; week 8: −0.75, −0.08; week 16: −0.40, −0.10; week 24: −0.50, 0.05.