Safety and Efficacy of CBT-001 Ophthalmic Solution in Patients With Pterygium

Study Overview
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Brief Summary
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Stage 1: Single Ascending Dose, Safety, Tolerability and Pharmacokinetics (n=24) Stage 2: Multiple Dose, Safety and Efficacy Study with 28-day Dosing and 5 months Followup (n=51)

Detailed Description
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Stage 1: Single Ascending Dose, Safety, Tolerability and Pharmacokinetics (n=24) Objectives are to evaluate ocular safety and tolerability by biomicroscopy, ophthalmoscopy, intraocular pressure and visual acuity, and to assess general safety by physical exams, vital signs, clinical laboratory tests and adverse events reporting and to evaluate systemic CBT-001 exposure by Cmax, Tmax and an estimation of the area under the curve (AUC). Three dose cohorts will be planned with a dose ascending strategy to guide dose concentrations (n=8 per Cohort x 3 cohorts = 24). Primary pterygium patients will be selected in this phase because the main goal is to assess the safety and tolerability of CBT-001 and primary pterygium patients are much easier to recruit. The  8 primary pterygium patients from each Cohort will be administered a single ocular drug dose at Day 1 in the eye with primary pterygium; the unaffected eye will be dosed with vehicle. Examinations will be performed at both screening day (Day 0) and Day 1. Blood samples at pre-dose, 0.25, 0.5, 1, 2, 4 and 8 hours post dose will be taken at Day 1 to assess systemic pharmacokinetics (PK). The data will be reviewed by Data Review Committee (DRC) to determine whether to initiate enrollment for the next Cohort. Cohort 1 will begin at the lowest CBT-001 concentration of 0.02%, followed by an increasing dose to 0.05% for Cohort 2 and then to 0.2% for Cohort 3. If no safety issues are found at all doses, the highest dose of 0.2% will be used for the next phase study. Stage 2: Multiple Dose, Safety and Efficacy Study with 28-day Dosing and 5 months Followup (n=51) Objectives are to evaluate ocular and systemic safety of CBT-001 in primary or recurrent patients that have moderate to severe pterygium vascularity and to assess whether CBT-001 is efficacious in reducing pterygium vascularity and pterygium lesion growth. The dosing will be 4 weeks. The followup period will be 5 months. Study Population Characteristics: Approximately 50 (30 primary pterygium and 20 recurrent) patients will be enrolled at up to 3 centers to have an estimated 40 patients complete the study based on an anticipated dropout rate of 20%. Although we have no evidence to suggest attrition due to Adverse Effects (AEs), the dropout rate is most conservative based on industry experience in comparable clinical studies. Patients will be randomized in a 1:1 treatment allocation to receive either CBT-001 0.2% or Vehicle. Dosage/Dose regimen: One drop of the assigned study medication will be administered in the study eye TID for 4 weeks. The study eye is defined as the qualified eye (i.e., the eye meeting the inclusion criterion for primary or recurrent pterygium). If both eyes are qualified, then the eye with the more severe vascularity grade on the Pterygium Hyperemia Grading Scale at the baseline (Day 1) visit will be the study eye. If both eyes meet the criterion and have the same severity, the right eye will be the study eye. Patients with bilateral pterygium will administer study medication only in the study eye. The fellow eyes in all study subjects will be untreated.

Official Title
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A Phase 2a 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

Conditions
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Pterygium

Intervention / Treatment
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* Drug: CBT-001 single dose
* Drug: Vehicle
* Drug: CBT-001 Multi-dose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Primary pterygium with moderate vascularity (Pterygium Hyperemia Grading Scale ≥ 3) Exclusion Criteria: Active ocular disease, corneal abnormalities other than pterygium, active ocular infection, or any ocular pathology unrelated to pterygium in either eye that could affect the assessment of the pterygium History of ocular herpes disease in either eye Any ocular surgical procedure within the last 3 months Female patients who are pregnant, nursing, or planning a pregnancy during the study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CBT-001 Ophthalmic Solution Single dose<br>One drop in the study administered one time only for one day | Drug: CBT-001 single dose<br>* One drop in the study administered one time<br>|
| Placebo Comparator: Vehicle<br>One drop in the study administered three times daily (TID) for 4 weeks | Drug: Vehicle<br>* One drop in the study administered three times daily (TID) for 4 weeks<br>|
| Experimental: CBT-001 Ophthalmic Solution Multidose<br>One drop in the study administered three times daily (TID) for 4 weeks | Drug: CBT-001 Multi-dose<br>* One drop in the study administered three times daily (TID) for 4 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pterygium Vascularity Change Assessed Using the Pterygium Hyperemia Grading Scale | The primary efficacy variable is the change from baseline (Day 1) in severity grade of pterygium vascularity at Week 4. Pterygium vascularity intensity is based on color coordinates as measured by digital image analysis of pterygium photographs. The quantitative analysis of photographs using a 5-point Pterygium Hyperemia Grading Scale (0 = absent, 1 = trace, 2 = mild, 3 = moderate, 4 = severe) will be conducted at an independent image reading center. | Change from baseline at 4 weeks | 
| Ocular and General Safety and Tolerability | The ocular safety and tolerability are measured by biomicroscopy, ophthalmoscopy, intraocular pressure and visual acuity, and to assess general safety by physical exams, vital signs, clinical laboratory tests and adverse events reporting | One day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Corneal Pterygium Lesion Length Change From Baseline | The Corneal Pterygium Lesion Length is measured from digital images of the eye by an independent image reading center. | 4 weeks |