Safety and Exploratory Efficacy Study of SF0166 for the Treatment of Diabetic Macular Edema (DME)

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 Diabetic Macular Edema (DME).

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 active Diabetic Macular Edema (DME) 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 Diabetic Macular Edema (DME)

Conditions
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Diabetic Macular Edema

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, 18 years of age or older. Retinal thickening secondary to type 1 or type 2 diabetes mellitus with Diabetic Macular Edema (DME) defined as central subfield thickness ≥325 microns (µm) on spectral domain OCT in the study eye. 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 Diabetic Macular Edema (DME). 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: Active proliferative diabetic retinopathy (PDR) in the study eye, such as neovascularization of the optic disc (NVD), neovascularization elsewhere (NVE), vitreous hemorrhage, or neovascular glaucoma. 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. Screening glycated hemoglobin (HbA1c) blood test >12.0%. Previous panretinal photocoagulation (PRP) in the study eye within 4 months of study enrollment, or the need for PRP during the study based on the Investigator's opinion. Previous focal laser photocoagulation in the study eye, within the foveal avascular zone. Intravitreal/periocular/topical ocular steroids of any type in the study eye within 90 days (3 months) prior to study enrollment. Placement of Iluvien or Retisert (fluocinolone acetonide intravitreal implant) in the study eye within 36 months (3 years) prior to study enrollment. Use of Ozurdex (dexamethasone intravitreal implant) in the study eye within 180 days (6 months) prior to study enrollment. Significant epiretinal membrane, posterior hyaloidal traction, and/or vitreomacular traction in the study eye as determined by the optical coherence tomography (OCT) results. 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. Concomitant use of 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. High myopia in the study eye, with a spherical equivalent of >8.00 Diopters (D) at screening. 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 the subject's vision in the study eye.

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: 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 Ophthalmic Solution;|
| 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 Ophthalmic Solution;|

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 | Percentage of subjects with red blood cell counts in the anterior chamber in the ranges from 0 to > 30 with the higher number being worse | Baseline, 2, 4, 6, and 8 weeks | 
| 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, 2, 4, 6, and 8 weeks | 
| Number of Subjects With Hyphema Observed Following Slit Lamp Examination From Baseline to Week 8 | Number and percentage of subjects with hyphema | Baseline, 2, 4, 6 and 8 weeks | 
| Number of Subjects With Bulbar Conjunctival Injection Observed Following Slit Lamp Examination From Baseline to Week 8 | Number and percentage of subjects with bulbar conjunctival injection | Baseline, 2,4,6 and 8 weeks | 
| Number of Subjects With Erythema Observed Following Slit Lamp Examination From Baseline to Week 8 | Number and percentage of subjects with erythema | Baseline, 2, 4, 6 and 8 weeks | 
| Number of Subjects With Edema Observed Following Slit Lamp Examination From Baseline to Week 8 | Number and percentage of subjects with edema | Baseline, 2,4, 6 and 8 weeks | 
| 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, 2,4,6 and 8 weeks | 
| 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, 2,4,6 and 8 weeks | 
| Number of Subjects With Abnormal Findings in Vitreous Following Fundus Examination From Baseline to Week 8 | Number and percentage of subjects (both eyes) with abnormal findings in the vitreous | Baseline, 2,4,6 and 8 weeks | 
| 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, 2,4,6 and 8 weeks | 
| 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, 2,4,6 and 8 weeks | 
| 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, 2,4,6 and 8 weeks | 
| 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 0.6 with the higher number being worse | Baseline, 2,4,6 and 8 weeks | 
| Number of Subjects With Abnormal Findings Following A Fluorescein Angiogram at Week 4 Compared to Baseline (Day 0) | Number and percentage of subjects with abnormal fluorescein angiogram findings | Baseline and 4 weeks | 
| Change in Intraocular Pressure From Baseline to Week 8 | Mean and standard deviation of change from Baseline in intra-ocular pressure | 2,4,6 and 8 weeks | 
| Change in Central Retinal Thickness (CRT) for Study Eye From Baseline (Day 0) to Week 8 |  | 2,4,6 and 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Best-corrected Visual Acuity (BCVA) for Study Eye From Baseline (Day 0) at Week 4 and Week 8 |  | 2, 4, 6 and 8 weeks |