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

• ClinicalTrials.gov Identifier: NCT02914613
• Recruitment Status: Completed
• First Posted: September 26, 2016
• Last Update Posted: June 1, 2017
• Sponsor: OcuTerra Therapeutics, Inc.
• Information provided by (Responsible Party): OcuTerra Therapeutics, Inc.

Study Description

Brief Summary:

The primary purpose of this study is to evaluate the safety and exploratory efficacy of SF0166 Topical Ophthalmic Solution in patients with Diabetic Macular Edema (DME).

Condition or disease	Intervention/treatment	Phase
Diabetic Macular Edema	Drug: SF0166 Topical Ophthalmic Solution	Phase 1; Phase 2

Detailed Description:

This is a prospective, randomized, double-masked, multicenter, Phase I/II clinical study in which up to 40 eligible subjects with active Diabetic Macular Edema (DME) will be 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.

The study population will include male and female subjects, aged 18 or older, with diabetic macular edema (i.e., retinal thickening secondary to type 1 or type 2 diabetes mellitus with Diabetic Macular Edema (DME) with central subfield thickness ≥325 microns (μm) on spectral domain optical coherence tomography [OCT]) and no treatment with antivascular endothelial growth factor (VEGF) therapy in the study eye within up to 60 days of study entry.

If a subject qualifies in both eyes, SF0166 may be administered to both eyes (study eye and non-study eye) at the discretion of the Investigator.

Study subjects will administer the randomly assigned treatment for 28 days. There is an additional 28-day post-treatment follow-up period. All study subjects will return for examination every 2 weeks for 8 weeks (2 months).

All outcomes and assessments will be summarized descriptively for Days 0, 14, 28, 42, and 56. No formal hypotheses will be tested.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 44 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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)
• Actual Study Start Date: August 24, 2016
• Actual Primary Completion Date: May 16, 2017
• Actual Study Completion Date: May 16, 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: SF0166 low dose BID; SF0166 low dose will be instilled in study eye BID for 28 days of treatment.	Drug: SF0166 Topical Ophthalmic Solution
Experimental: SF0166 high dose BID; SF0166 high dose will be instilled in study eye BID for 28 days of treatment.	Drug: SF0166 Topical Ophthalmic Solution

Outcome Measures

Primary Outcome Measures :

1. Safety: Best-corrected Visual Acuity (BCVA) Change from Day 0 to Day 56 [ Time Frame: Assessed at Days 0, 14, 28, 42, and 56 ]
   Assessed with Early Treatment Diabetic Retinopathy Study (ETDRS) method. Descriptive presentation of number of subjects with clinically significant changes from Baseline (Day 0) through Day 56 in BCVA.
2. Safety: Slit-lamp Findings Change from Day 0 to Day 56 [ Time Frame: Assessed at Days 0, 14, 28, 42, and 56 ]
   Areas to be assessed include conjunctiva, cornea, anterior chamber, and lens; determination of normal or abnormal made by Investigators. Descriptive presentation of number of subjects with clinically significant changes from Baseline (Day 0) through Day 56 in abnormal slit-lamp findings.
3. Safety: Fundus Findings Change from Day 0 to Day 56 [ Time Frame: Assessed at Days 0, 14, 28, 42, and 56 ]
   Areas to be assessed include vitreous, fundus, optic nerve, cup to disc ratio, macula and choroid, vessels and peripheral retina; determination of normal or abnormal made by Investigators. Descriptive presentation of number of subjects with clinically significant changes from Baseline (Day 0) through Day 56 in abnormal fundus findings.
4. Safety: Intraocular Pressure (IOP) Change from Day 0 to Day 56 [ Time Frame: Assessed at Days 0, 14, 28, 42, and 56 ]
   Measured in millimeters of mercury (mmHg) by Tonopen or Applanation. Descriptive presentation of number of subjects with clinically significant changes from Baseline (Day 0) through Day 56 in IOP.
5. Safety: Adverse Events (AEs) Change from Day 0 to Day 56 [ Time Frame: Assessed at Days 0, 14, 28, 42, and 56 ]
   Ocular and non-ocular events collected and summarized descriptively; presentation of number of subjects with reported adverse events or serious adverse events.

Secondary Outcome Measures :

1. Primary Efficacy: Mean Change in Anatomic Center Subfield Thickness from Day 0 to Days 14, 28, 42, and 56 [ Time Frame: Days 0, 14, 28, 42, and 56 ]
   Measured in microns (μm) by optical coherence tomography (OCT). Descriptive presentation at each study visit time point; no hypothesis testing.
2. Primary Efficacy: Mean Change in Macular Volume from Day 0 to Days 14, 28, 42, and 56 [ Time Frame: Days 0, 14, 28, 42, and 56 ]
   Measured in cubic millimeters (mm3) by optical coherence tomography (OCT). Descriptive presentation at each study visit time point; no hypothesis testing.
3. Secondary Efficacy: Mean Change in Best-corrected Visual Acuity (BCVA) from Day 0 to Days 14, 28, 42, and 56 [ Time Frame: Days 0, 14, 28, 42, and 56 ]
   Assessed with Early Treatment Diabetic Retinopathy Study (ETDRS) method. Descriptive presentation at each study visit time point; no hypothesis testing.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Male or female, 18 years of age or older.
2. 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.
3. 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).

4. 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:

   1. Lucentis (ranibizumab): 30-day washout
   2. Avastin (bevacizumab): 30-day washout
   3. Eylea (aflibercept): 60-day washout
   4. Macugen (pegaptanib): 45-day washout
5. Willing and able to return for all study visits.
6. Able to adhere to the study dosing requirements.
7. Understands and signs the written informed consent form.

Exclusion Criteria:

1. 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.
2. 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.
3. 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.
4. Screening glycated hemoglobin (HbA1c) blood test >12.0%.
5. 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.
6. Previous focal laser photocoagulation in the study eye, within the foveal avascular zone.
7. Intravitreal/periocular/topical ocular steroids of any type in the study eye within 90 days (3 months) prior to study enrollment.
8. Placement of Iluvien or Retisert (fluocinolone acetonide intravitreal implant) in the study eye within 36 months (3 years) prior to study enrollment.
9. Use of Ozurdex (dexamethasone intravitreal implant) in the study eye within 180 days (6 months) prior to study enrollment.
10. Significant epiretinal membrane, posterior hyaloidal traction, and/or vitreomacular traction in the study eye as determined by the optical coherence tomography (OCT) results.
11. Previous pars plana vitrectomy in the study eye.
12. Any intraocular surgery in the study eye within 90 days (3 months) prior to study enrollment.
13. Yttrium aluminium garnet (YAG) laser treatment in the study eye within 30 days (1 month) prior to study enrollment.
14. 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.
15. High myopia in the study eye, with a spherical equivalent of >8.00 Diopters (D) at screening.
16. Chronic or recurrent uveitis in the study eye.
17. Ongoing ocular infection or inflammation in either eye.
18. A history of cataract surgery complicated by vitreous loss in the study eye.
19. Congenital eye malformations in the study eye.
20. A history of penetrating ocular trauma in the study eye.
21. Mentally handicapped.
22. 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.
23. Participation in any other investigational device or drug clinical research study within 30 days of Visit 1 - Screening/Randomization.
24. Contraindication to the study medications or fluorescein dye.
25. Other ocular pathologies that in the Investigator's opinion would interfere with the subject's vision in the study eye.

Contacts and Locations

Locations

United States, California

Retina-Vitreous Associates Medical Group

Beverly Hills, California, United States, 90211

United Medical Research Institute

Inglewood, California, United States, 90301

Martel Eye Medical Group

Rancho Cordova, California, United States, 95670

United States, Florida

Center for Retina and Macular Disease

Winter Haven, Florida, United States, 33880

United States, Massachusetts

Ophthalmic Consultants of Boston

Boston, Massachusetts, United States, 02114

United States, Texas

Retina Consultants of Houston

Houston, Texas, United States, 77030

Sponsors and Collaborators

OcuTerra Therapeutics, Inc.

Investigators

• Study Chair: Gary Foulks, MD; Medical Monitor

More Information

• Responsible Party: OcuTerra Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT02914613
• Other Study ID Numbers: SF0166-C-001
• First Posted: September 26, 2016
• Last Update Posted: June 1, 2017
• Last Verified: May 2017

Additional relevant MeSH terms:

Macular Edema; Edema; Macular Degeneration; Retinal Degeneration; Retinal Diseases; Eye Diseases; Ophthalmic Solutions; Pharmaceutical Solutions