Safety and Exploratory Efficacy Study of SF0166 in the Treatment of Neovascular Age-Related Macular Degeneration (AMD)

Study Overview
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Brief Summary
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The primary purpose of this study was to evaluate the safety and exploratory efficacy of SF0166 Topical Ophthalmic Solution in patients with Neovascular (wet) Age-related Macular Degeneration (AMD).

Detailed Description
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This was a prospective, randomized, double-masked, multicenter, Phase I/II clinical study in which 44 eligible subjects with Neovascular Age-related Macular Degeneration (AMD) were randomized to 1 of 2 treatment arms in a 1:1 ratio as follows: SF0166 low dose twice daily (BID) or SF0166 high dose BID. Study subjects administered the randomly assigned treatment for 28 days. There was an additional 28-day post-treatment follow-up period. Study subjects returned for examination every 2 weeks for 8 weeks (2 months).

Official Title
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A Phase I/II Randomized, Double-Masked, Multicenter Clinical Trial Designed to Evaluate the Safety and Exploratory Efficacy of SF0166 Topical Ophthalmic Solution in the Treatment of Neovascular Age-Related Macular Degeneration (AMD)

Conditions
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Age-Related Macular Degeneration

Intervention / Treatment
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* Drug: SF0166 Topical Ophthalmic Solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, 50 years of age or older. Active subfoveal choroidal neovascularization due to Age-related Macular Degeneration (AMD) in the study eye that meet the following criteria: Total lesion ≤12 Macular Photocoagulation Study (MPS) disc areas Choroidal neovascularization (CNV) >50% of lesion area Intraretinal or subretinal fluid due to choroidal neovascularization (CNV) visible on optical coherence tomography (OCT) No atrophy or fibrosis involving the center of the fovea Best-corrected Visual Acuity (BCVA) between 78 and 25 letters, inclusive, in the study eye at the screening/randomization visit using Early Treatment Diabetic Retinopathy Study (ETDRS) testing, with BCVA decrement primarily attributable to neovascular Age-related Macular Degeneration (AMD). Treatment naïve (i.e., no previous anti--vascular endothelial growth factor [VEGF] treatment in the study eye) or previously treated study eye with adequate washout defined below: Lucentis (ranibizumab): 30-day washout Avastin (bevacizumab): 30-day washout Eylea (aflibercept): 60-day washout Macugen (pegaptanib): 45-day washout Willing and able to return for all study visits. Able to adhere to the study dosing requirements. Understands and signs the written informed consent form. Exclusion Criteria: Non-study eye best corrected visual acuity (BCVA) worse than 20 letters at the screening/randomization visit using Early Treatment Diabetic Retinopathy Study (ETDRS) testing. Choroidal neovascularization (CNV) in the study eye secondary to other causes (e.g., pathologic myopia, ocular histoplasmosis syndrome, angioid streaks, choroidal rupture, posterior uveitis, or multifocal choroiditis). Previous macular laser photocoagulation or ocular photodynamic therapy in the study eye. Media opacities or abnormalities in the study eye that would preclude visualization of the retina. Other retinal pathologies in the study eye that would interfere with vision. Retinal pigment epithelial (RPE) tear in the study eye. Significant epiretinal membrane, posterior hyaloidal traction, and/or vitreomacular traction in the study eye as determined by optical coherence tomography (OCT) results. Uncontrolled glaucoma or ocular hypertension in the study eye defined as an Intraocular Pressure (IOP) >25 millimeter of mercury (mmHg) regardless of concomitant treatment with IOP lowering medications. Uncontrolled hypertension defined as systolic >180 mmHg or >160 mmHg on 2 consecutive measurements (during the same visit) or diastolic >100 mmHg on optimal medical regimen Previous pars plana vitrectomy in the study eye. Any intraocular surgery in the study eye within 90 days (3 months) prior to study enrollment. Yttrium aluminium garnet (YAG) laser treatment in the study eye within 30 days (1 month) prior to study enrollment. Intravitreal/periocular/topical ocular steroids of any type in the study eye within 90 days (3 months) prior to study enrollment. Concomitant use any topical ophthalmic medications in the study eye, including dry eye or glaucoma medications, unless on a stable dose for at least 90 days (3 months) prior to study enrollment and expected to stay on stable dose throughout study participation. Artificial tears are allowed. Chronic or recurrent uveitis in the study eye. Ongoing ocular infection or inflammation in either eye. A history of cataract surgery complicated by vitreous loss in the study eye. Congenital eye malformations in the study eye. A history of penetrating ocular trauma in the study eye. Mentally handicapped. Females of childbearing potential (i.e., who are not postmenopausal for at least 1 year or surgically sterile for at least 6 weeks prior to Visit 1 - Screening/Randomization) who are lactating, or who are pregnant as determined by a positive urine pregnancy test (UPT) at Visit 1 - Screening/Randomization. Women of childbearing potential must agree to use acceptable methods of birth control throughout the study. Acceptable methods of birth control include tubal ligation, transdermal patch, intrauterine devices/systems, oral/implantable/injectable or contraceptives, sexual abstinence, double barrier method, or vasectomized partner. Participation in any other investigational device or drug clinical research study within 30 days of Visit 1 - Screening/Randomization. Contraindication to the study medications or fluorescein dye. Other ocular pathologies that in the Investigator's opinion would interfere with vision in the study 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: SF0166 low dose BID<br>SF0166 low dose instilled in study eye BID for 28 days of treatment. | Drug: SF0166 Topical Ophthalmic Solution<br> <br> * Other names: OTT166;|
| Experimental: SF0166 high dose BID<br>SF0166 high dose instilled in study eye BID for 28 days of treatment. | Drug: SF0166 Topical Ophthalmic Solution<br> <br> * Other names: OTT166;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With No Cells Observed Following Slit Lamp Examination From Baseline to Week 8 | Number and percentage of subjects with no red blood cell counts in the anterior chamber | Baseline, Week 2, Week 4, Week 6 and Week 8 | 
| Number of Subjects With Flare Observed Following Slit Lamp Examination From Baseline to Week 8 | Number and percentage of subjects with flare in the anterior chamber graded on a scale from 0 (none) to 4 (severe) | Baseline, Week 2, Week 4, Week 6 and Week 8 | 
| Number of Subjects With Absence of Hyphema Observed Following Slit Lamp Examination From Baseline to Week 8 | Number and percentage of subjects with absence of hyphema | Baseline, Week 2, Week 4, Week 6 and Week 8 | 
| Number of Subjects With Absence of Bulbar Conjunctival Injection Observed Following Slit Lamp Examination From Baseline to Week 8 | Number and percentage of subjects with absence of bulbar conjunctival injection | Baseline, Week 2, Week 4, Week 6 and Week 8 | 
| Number of Subjects With Absence of Erythema Observed Following Slit Lamp Examination From Baseline to Week 8 | Number and percentage of subjects with absence of erythema | Baseline, Week 2, Week 4, Week 6 and Week 8 | 
| Number of Subjects With Absence of Edema Observed Following Slit Lamp Examination From Baseline to Week 8 | Number and percentage of subjects with absence of edema | Baseline, Week 2, Week 4, Week 6 and Week 8 | 
| Number of Subjects With Any Lens Opacity Observed Following Slit Lamp Examination From Baseline to Week 8 | Number and percentage of subjects with any lens opacity | Baseline, Week 2, Week 4, Week 6 and Week 8 | 
| Number of Subjects With Abnormal Findings in Optic Nerve Following Fundus Examination From Baseline to Week 8 | Number and percentage of subjects with abnormal findings in the optic nerve | Baseline, Week 2, Week 4, Week 6 and Week 8 | 
| Number of Subjects With Abnormal Findings in Vitreous Following Fundus Examination From Baseline to Week 8 | Number and percentage of subjects with abnormal findings in the vitreous | Baseline, Week 2, Week 4, Week 6 and Week 8 | 
| Number of Subjects With Abnormal Findings in Fundus Following Fundus Examination From Baseline to Week 8 | Number and percentage of subjects with abnormal findings in the fundus | Baseline, Week 2, Week 4, Week 6 and Week 8 | 
| Number of Subjects With Abnormal Findings in Macula/Choroid Following Fundus Examination From Baseline to Week 8 | Number and percentage of subjects with abnormal findings in the macula/choroid | Baseline, Week 2, Week 4, Week 6 and Week 8 | 
| Number of Subjects With Abnormal Findings in Vessels Following Fundus Examination From Baseline to Week 8 | Number and percentage of subjects with abnormal findings in the retinal vessels | Baseline, Week 2, Week 4, Week 6 and Week 8 | 
| Cup:Disc Ratio of Subjects Following Fundus Examination From Baseline to Week 8 | Number and percentage of subjects with specified Cup:Disc ratio in the range from 0.1 to 0.9 with the higher number being worse | Baseline, Week 2, Week 4, Week 6 and Week 8 | 
| Number of Subjects With Abnormal Findings Following A Fluorescein Angiogram at Week 4 Compared to Baseline | Number and percentage of subjects with abnormal fluorescein angiogram findings | Baseline and Week 4 | 
| Change in Intraocular Pressure From Baseline to Week 8 | Mean and standard deviation of change from Baseline in intra-ocular pressure | Week 2, Week 4, Week 6 and Week 8 | 
| Change in Study Eye Central Retinal Thickness (CRT) From Baseline (Day 0) to Week 8 | Results are mean plus standard deviation | Week 2, Week 4, Week 6 and Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Best-corrected Visual Acuity (BCVA) From Baseline (Day 0) at Week 4 and Week 8 | Results are mean plus standard deviation in per protocol population. | Week 2, Week 4, Week 6, and Week 8 |