Study of Squalamine Lactate for the Treatment of Macular Edema Related to Retinal Vein Occlusion

Open Label Squalamine Lactate Ophthalmic Solution for the Treatment of Macular Edema Secondary to Branch Retinal Vein Occlusion (BRVO) and Central Retinal Vein Occlusion (CRVO)

This was a prospective, single center, open label, randomized study evaluating the biological effect of squalamine lactate ophthalmic solution, 0.2% combined with intravitreous ranibizumab in patients with macular edema secondary to branch, hemi-central and central retinal vein occlusion (BRVO, HRVO, CRVO).

Study Overview

• Status: Completed
• Conditions: Macular Edema; Retinal Vein Occlusion
• Intervention / Treatment: Drug: ranibizumab; Drug: Squalamine Lactate Ophthalmic Solution, 0.2%

Detailed Description

At baseline, all eyes underwent ETDRS visual acuity measurements at 4 meters, a complete ophthalmological evaluation, SD-OCT imaging of the macula, and fluorescein angiographic assessment of capillary perfusion in the macula and peripheral fundus. All eyes received an initial 10 week mandatory loading period of topical squalamine therapy.

All eyes received mandatory intravitreal injections of ranibizumab 0.5mg at the conclusions of weeks 2 and 6. At the conclusion of week 10, eyes were randomized in a 1:1 ratio to continue squalamine drops bid or discontinue squalamine drops in the study eye. All eyes were examined every 4 weeks through the week 38 endpoint and were eligible to receive additional as needed ranibizumab 0.5mg injections starting at the conclusion of week 10 and every 4 weeks thereafter through week 34 depending upon prespecified visual acuity and OCT retreatment criteria.

Any eye with a decrease of 5 or more ETDRS letters or increase in CST on OCT of 50uM or more from their best previous measurements automatically received an additional ranibizumab 0.5mg injection beginning at the conclusion of week 10.

Eyes randomized to continue squalamine drops did so through the week 38 endpoint. SD-OCT measurements of the macula were obtained at every study visit. Fluorescein angiograms were performed on the study eye at baseline, weeks 10 and 38.

Safety endpoints included all adverse events spontaneously reported, elicited or observed were documented by the investigators at any visit.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2; Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Eyes with treatment naïve, center involving macular edema secondary to BRVO, HRVO or CRVO in patients of at least 40 years of age
• Macular edema of 1-4 months duration prior to the baseline visit
• Best corrected baseline ETDRS visual acuity of 20/40 to 20/320 Snellen equivalent using the 4 meter testing method
• Baseline CST greater than or equal to 325uM using SD-OCT imaging
• Less than 50% foveal capillary ring disruption as defined by fluorescein angiography (FA)
• Absence of dense intraretinal or subretinal hemorrhage and or lipid through the foveal center
• Absence of subfoveal fibrosis or hyperpigmentation.

Exclusion Criteria:

• Eyes with ocular pathology other than RVO related macular edema such as clinically significant cataract or media opacity, diabetic retinopathy, macular degeneration, glaucoma, uveitis, epiretinal membrane, vitreomacular traction or intraocular tumor
• Intraocular surgery within 6 months prior to baseline
• Two-plus or greater afferent pupillary defect (APD) in the study eye
• Likelihood of evidence driven indication for peripheral scatter photocoagulation within 6 months of recruitment
• History of previous intravitreal pharmacologic treatment of any kind in the study eye
• History of previous retinal laser photocoagulation of any kind in the study eye
• History of intravitreal anti-VEGF therapy in the fellow eye within 6 months prior to baseline
• Any evidence of baseline ocular neovascularization such as disc neovascularization, preretinal neovascularization, iris or angle neovascularization in the study eye
• Eyes that have shown spontaneous improvement within the preceding 3 months defined as an improvement of best corrected visual acuity of greater than 15 ETDRS letters or thinning of the CST on OCT of greater than 20%

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Squalamine and ranibizumab to Week 10; All eyes received an initial 10 week mandatory loading period of topical Squalamine Lactate Ophthalmic Solution, 0.2% therapy. All eyes received mandatory intravitreal injections of ranibizumab 0.5mg at the conclusions of weeks 2 and 6. Randomize at Week 10 to 2 different groups - Squalamine and No Squalamine, continue PRN ranibizumab in both groups	Drug: ranibizumab; 0.5 mg IVT ranibizumab; Other Names: Lucentis; Drug: Squalamine Lactate Ophthalmic Solution, 0.2%; Squalamine Lactate Ophthalmic Solution BID
Experimental: Continue Squalamine, ranibizumab PRN; Continue use of Squalamine Lactate Ophthalmic Solution, 0.2% after Week 10; continue ranibizumab 0.5 mg IVT PRN	Drug: ranibizumab; 0.5 mg IVT ranibizumab; Other Names: Lucentis
Experimental: Stop Squalamine, ranibizumab PRN; Discontinue use of Squalamine Lactate Ophthalmic Solution, 0.2% after Week 10; continue ranibizumab 0.5 mg IVT PRN	Drug: ranibizumab; 0.5 mg IVT ranibizumab; Other Names: Lucentis; Drug: Squalamine Lactate Ophthalmic Solution, 0.2%; Squalamine Lactate Ophthalmic Solution BID

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Visual Function - Efficacy	Mean change in ETDRS letter score from baseline	Baseline to Week 38

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Visual Function - Efficacy	Eyes with visual outcomes of 20/40 or better at Week 38 compared to Baseline Visit	Baseline to Week 38
Retinal Anatomy - Efficacy	Proportion of eyes with Central Subfield Thickness (CST) on SD-OCT less than 325 microns at Week 38	Baseline to Week 38
Safety and Tolerability as measured by adverse event reporting and ophthalmologic examination from Baseline to Week 38	Safety as measured by adverse event reporting and ophthalmologic examination from Baseline to Week 38	Baseline to Week 38
Concomitant ranibizumab administration - efficacy	Number of injections of 0.5 mg ranibizumab to keep edema resolved from Week 2 through Week 34 of study	Baseline to Week 38

Collaborators and Investigators

• Sponsor: Ohr Pharmaceutical Inc.
• Collaborators: Cumberland Valley Retina Consultants, PC
• Investigators: Principal Investigator: John Wroblewski, MD, Cumberland Valley Retinal Consultants, Hagerstown, MD

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: November 23, 2015
• First Submitted That Met QC Criteria: November 24, 2015
• First Posted (Estimate): November 25, 2015

Study Record Updates

• Last Update Posted (Estimate): November 25, 2015
• Last Update Submitted That Met QC Criteria: November 24, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Eye Diseases; Retinal Degeneration; Retinal Diseases; Embolism and Thrombosis; Venous Thrombosis; Thrombosis; Macular Degeneration; Macular Edema; Retinal Vein Occlusion; Edema; Physiological Effects of Drugs; Anti-Infective Agents; Antineoplastic Agents; Protective Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Anti-Bacterial Agents; Pharmaceutical Solutions; Anticarcinogenic Agents; Ranibizumab; Ophthalmic Solutions; Squalamine
• Other Study ID Numbers: OHR-004