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

翼状胬肉是一种眼表疾病，角膜上有异常的纤维血管生长，影响约10 在美国有一百万人。晚期疾病损害视力，目前的护理标准是外科手术。 切除病变组织。然而，约10%的患者术后病变复发。因为没有 批准的治疗翼状胬肉的药物，我们建议用一种局部眼药来解决这一未得到满足的医疗需求。 我们已经研制出一种局部滴眼液九替达尼，这是一种小分子多激酶抑制剂(MKI)，其靶向是 生长因子参与了翼状胬肉的发病机制。九替丹尼是一种有效的药物成分。 OFEV®，FDA批准的治疗特发性肺纤维化的口服药物。我们已经证明了我们的公式 9tedanib，CBT-001，抑制兔角膜缝线模型中的角膜新生血管及其原因 免疫缺陷小鼠眼睛上生长的人翼状胬肉病变组织的消退。这些结果产生了 使我们能够在全球范围内申请九替达尼治疗翼状胬肉的使用方法专利。我们有 我们成功地向FDA提交了IND申请，并已获准在#年进行临床试验 美国。我们的监管策略采用505(B)2路径，参考现有的人类安全性、药动学 以及OFEV®的非临床研究结果。我们的私人天使基金200万美元使我们能够完成所有 支持IND的临床前研究，并将部分支持拟议的临床试验。 此Fast Track应用程序的第一阶段目标是：(1)评估眼睛和系统的安全性和耐受性 以及单次眼局部应用CBT-001对翼状胬肉血管的影响 (2)测定CBT-001的全身药代动力学，并选择 CBT-001滴眼液单次眼部局部给药后的最高安全剂量 翼状胬肉患者。我们的第二阶段目标是：(1)评价CBT-001在小学的眼部和全身安全性 以及TID期间和术后复发的翼状胬肉患者，28天重复眼部给药；(2)评估 CBT-001在初发和复发性翼状胬肉患者TID中和术后，重复28天眼部给药。我们 将确定CBT-001是否可以(I)减少翼状胬肉的关键症状，即角膜上血管异常 通过使用标准化的5点翼状胬肉充血分级量表分析眼部照片来分析结膜和结膜； 通过测量眼部照片中翼状胬肉的角膜病变长度、宽度和面积来稳定或消退病变； 改善患者的生活质量；以及(Iv)改善翼状胬肉病变引起的散光。 这个为期两年的研究计划的项目里程碑是完成2a阶段的多中心、随机、 评价CBT-001安全性、有效性和药代动力学的车辆对照剂量递增研究 翼状胬肉患者用滴眼液。如果CBT-001被证明在临床上是安全有效的 获准上市，它可能会显著改善翼状胬肉患者的治疗，通过减少 减少手术干预次数，降低术后疾病复发风险。

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.