A Phase 2a Multicenter, Randomized, Vehicle-Controlled, Dose Escalating Study to Evaluate the Safety, Efficacy and Pharmacokinetics of CBT-001 Ophthalmic Solution in Pterygium Patients

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Pterygium is an ocular surface disease with abnormal fibrovascular growth on the cornea that affects about 10 million individuals in the US. Later-stage disease impairs vision and the current standard of care is surgical removal of lesion tissue. However, lesions recur in about 10% of patients after surgery. Because there is no approved drug to treat pterygium, we propose to address this unmet medical need with a topical ocular drug. We have formulated a topical eye drop nintedanib, a small molecule multikinase inhibitor (MKI) that targets growth factors implicated in pterygium pathogenesis. Nintedanib is the active pharmaceutical ingredient of Ofev®, an FDA-approved oral treatment for idiopathic pulmonary fibrosis. We have shown that our formulated nintedanib, CBT-001, suppresses cornea neovascularization in a rabbit corneal suture model and causes regression of human pterygium lesion tissue grown on the eyes of immune-deficient mice. These results have enabled us to globally file the method of use patent of nintedanib for pterygium treatment. We have successfully submitted our IND application to FDA and have been approved to proceed with a clinical trial in the US. Our regulatory strategy takes the 505(b)2 path by referencing existing human safety, pharmacokinetics and non-clinical study results of Ofev®. Our private angel funding of $2 million enabled us to complete all the IND-enabling pre-clinical studies and will partially support the proposed clinical trial. The Phase I Aims of this Fast Track application are to: (1) Evaluate ocular and systemic safety and tolerability as well as effect on pterygium vascularity after a single topical ocular administration of CBT-001 ophthalmic solution in primary pterygium patients; (2) Determine systemic pharmacokinetics of CBT-001 and select the highest safe dose after a single topical ocular administration of CBT-001 ophthalmic solution in primary pterygium patients. Our Phase II Aims are to: (1) Evaluate ocular and systemic safety of CBT-001 in primary and recurrent pterygium patients during and after TID, 28 day repeat ocular dosing; (2) Assess the efficacy of CBT-001 in primary and recurrent pterygium patients during and after TID, 28 day repeat ocular dosing. We will determine whether CBT-001 can (i) reduce the key pterygium symptom of abnormal vascularity on cornea and conjunctiva by analyzing eye photos using a standardized 5-point Pterygium Hyperemia Grading Scale; (ii) stabilize or regress lesion by measuring corneal lesion length, width and area of pterygium in eye photos; (iii) improve the quality of life of patients; and (iv) improve astigmatism caused by pterygium lesion. The Project Milestone for this two-year Research Plan is to complete a Phase 2a multicenter, randomized, vehicle-controlled, dose escalating study to evaluate the safety, efficacy and pharmacokinetics of CBT-001 ophthalmic solution in pterygium patients. If CBT-001 proves to be clinically safe and efficacious and is approved for marketing, it may significantly improve the treatment of pterygium patients by reducing the number of surgical interventions and lower the risk of post-surgical disease recurrence.