A Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of APP13007 to Treat Inflammation and Pain After Cataract Surgery

Study Overview
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Brief Summary
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This is a Phase 2a, 2-part study (designated Parts A and B) that will evaluate APP13007 dose strength and dosing frequency in a randomized double-masked fashion for comparison to the respective matching vehicle placebo. Part A will be conducted first to evaluate 0.05% APP13007 and matching vehicle placebo in an approximate 1:1 ratio in approximately 42 subjects who experience postoperative inflammation on the first day following routine, uncomplicated, cataract surgery and who meet all eligibility criteria. Based on the results of Part A, Part B of the study may be open for enrollment to evaluate 0.05% and/or 0.1% APP13007 at various dosing frequency in approximately 84 subjects, also in an approximate 1:1 ratio, active vs. placebo. In each Part, subjects will return periodically for study assessments during the treatment period and then for a follow-up visit approximately 1 week after stopping the study drug.

Official Title
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A Multicenter, Randomized, Double-Masked, Two-Part, Placebo-Controlled Phase 2A Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of APP13007 for the Treatment of Inflammation and Pain After Cataract Surgery

Conditions
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Ocular Inflammation and Pain After Cataract Surgery

Intervention / Treatment
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* Drug: APP13007, 0.05%
* Drug: APP13007, 0.1%
* Drug: APP13007 Placebo, 0.05%
* Drug: APP13007 Placebo, 0.1%


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Expected to undergo unilateral uncomplicated cataract extraction via phacoemulsification and posterior chamber intraocular lens implantation in one eye. In Investigator's opinion, have Early Treatment Diabetic Retinopathy Study estimated potential of 0.7 (20/100) or better in study eye. Have > 10 and ≤ 30 cells in anterior chamber. Have an intraocular pressure ≤ 30 mmHg. Exclusion Criteria: Have an anterior chamber cell count > 0 or any evidence of intraocular inflammation. Have a score > 0 on Ocular Pain Assessment in either eye.

Ages Eligible for Study
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Minimum Age: 50 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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: APP13007 0.05% twice daily (BID) [Part A]<br>1 drop 0.05% APP13007 twice daily for 21 days to the operated eye | Drug: APP13007, 0.05%<br>* APP13007 eye drop, 0.05%<br>|
| Experimental: APP13007 0.05% Placebo twice daily (BID) [Part A]<br>1 drop matching vehicle placebo for 0.05% APP13007 twice daily for 21 days to the operated eye | Drug: APP13007 Placebo, 0.05%<br>* APP13007 placebo eyedrop, 0.05%<br>|
| Experimental: APP13007 0.05% twice daily (BID) and once daily (QD) [Part B]<br>1 drop 0.05% APP13007 twice daily for 3 days followed by 1 drop once daily for 11 days to the operated eye | Drug: APP13007, 0.05%<br>* APP13007 eye drop, 0.05%<br>|
| Experimental: APP13007 0.05% Placebo twice daily (BID) and once daily (QD) [Part B]<br>1 drop matching vehicle placebo for 0.05% APP13007 twice daily for 3 days followed by 1 drop once daily for 11 days to the operated eye | Drug: APP13007 Placebo, 0.05%<br>* APP13007 placebo eyedrop, 0.05%<br>|
| Experimental: APP13007 0.1% twice daily (BID) and once daily (QD) [Part B]<br>1 drop 0.1% APP13007 twice daily for 3 days followed by 1 drop once daily for 11 days to the operated eye | Drug: APP13007, 0.1%<br>* APP13007 eye drop, 0.1%<br>|
| Experimental: APP13007 0.1% Placebo twice daily (BID) and once daily (QD) [Part B]<br>1 drop matching vehicle placebo for 0.1% APP13007 twice daily for 3 days followed by 1 drop once daily for 11 days to the operated eye | Drug: APP13007 Placebo, 0.1%<br>* APP13007 placebo eyedrop, 0.1%<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Treatment Emergent Adverse Events | Number of treatment emergent adverse events and number of participants. | From First dose to Post-operative Day 28 (Part A) or Day 22 (Part B) | 
| Intraocular Pressure - Change From Baseline (POD1 Prior to Dosing) to End-of-Treatment in the Operated Study Eye | Intraocular pressure is measured in mm Hg at each study visit with a Goldmann applanation tonometer. The change from baseline is calculated by subtracting the pretreatment measurement value from the value at each visit. | Baseline and Post-operative Day 22 (Part A) or Day 15 (Part B) | 
| Absolute Anterior Chamber Cell Count - Change From Baseline (POD1 Prior to Dosing) to POD 15 in the Operated Study Eye | The number of cells in the anterior chamber of the eye are counted using slit-lamp biomicroscopy at each study visit and the results are reported as number of cells in a 1mm x 1mm area. | Baseline and Post-operative Day 15 | 
| Visual Acuity - Change From Baseline (POD1 Prior to Dosing) to End-of Treatment in the Operated Study Eye | The visual acuity in each eye is corrected using the pinhole method and the acuity is quantified on a logMAR (minimal angle of resolution) scale using the 'Early Treatment Diabetic Retinopathy Study' [ETDRS] charts for right and left eyes. A logMAR Score is calculated using the number of incorrect letters. | Baseline and Post-operative Day 22 (Part A) or Day 15 (Part B) | 
| Ocular Pain Grade - Change From Baseline (POD1 Prior to Dosing) to POD15 in the Operated Study Eye | Ocular pain is measured in each eye using a subject-reported five-point (0-4) ocular pain grade scale (0 = no pain; 4 = severe pain). | Baseline and Post-operative Day 15 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subjects With Anterior Chamber Cell Count = 0 at POD15 in the Operated Study Eye Without Rescue Medication | The number of cells in the anterior chamber of the eye are counted using slit-lamp biomicroscopy at each study visit and the results are reported as number of cells in a 1mm x 1mm area. | Post-operative Day 15 | 
| Subjects With Ocular Pain Grade = 0 at POD 15 in the Operated Study Eye Without Rescue Medication | Ocular pain is measured in each eye using a subject-reported five-point (0-4) ocular pain grade scale (0 = no pain; 4 = severe pain). | Post-operative Day 15 | 
| Anterior Chamber Flare - Change From Baseline (POD1 Prior to Dosing) to End-of Treatment in the Operated Study Eye | The degree of turbidity (flare) in the anterior chamber of the eye is measured using slit-lamp biomicroscopy and quantified on a five-point (0-4) anterior chamber flare grade scale (0 = none; 4 = Intense). The change from baseline is calculated by subtracting the pretreatment measurement value from the value at each visit. | Baseline and Post-operative Day 22 (Part A) or Day 15 (Part B) | 
| Subjects Using of Anti-inflammatory 'Rescue' Medication Through End-of-Treatment | Subjects who do not respond to study treatment after randomization (anterior chamber cell count > 30 cells or an increase in anterior chamber cell count by > 15 cells from pre-dose baseline or ≥ 2 grade of increase in anterior chamber flare from pre-dose baseline) are started on anti-inflammatory medication (referred to as 'Rescue' medication). The number of subjects starting 'Rescue' medication is recorded at each study visit. | First dose to Post-operative Day 22 (Part A) or Day 15 (Part B) |