Squalamine Lactate Eye Drops in Combination With Ranibizumab in Patients With Diabetic Macular Edema (DME)

Study Overview
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Brief Summary
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A randomized, controlled study of the safety and efficacy of Squalamine Lactate Eye Drops in combination with Ranibizumab intravitreal injections in patients with diabetic macular edema. The study duration is 52 weeks and patients will be randomized to one of four treatment arms.

Detailed Description
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A randomized, controlled study of the safety and efficacy of Squalamine Lactate eye drops in combination with Ranibizumab intravitreal injections in patients with diabetic macular edema. Subjects will be randomized to one of the following treatment arms: Squalamine Lactate Ophthalmic Solution administered twice a day for 52 weeks in combination with monthly injections of ranibizumab from baseline through week 20 and ranibizumab as needed from week 24 through week 52. Vehicle Ophthalmic Solution administered twice a day for 52 weeks in combination with monthly injection of ranibizumab from baseline through week 20 and ranibizumab as needed from week 24 through week 52. Squalamine Lactate Ophthalmic Solution administered four times a day for 52 weeks in combination with monthly injections of ranibizumab from baseline through week 20 and ranibizumab as needed from week 24 through week 52. Vehicle Ophthalmic Solution administered four times a day for 52 weeks in combination with monthly injection of ranibizumab from baseline through week 20 and ranibizumab as needed from week 24 through week 52.

Official Title
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A Randomized, Controlled Study of the Safety and Efficacy of Squalamine Lactate Eye Drops in Combination With Ranibizumab in Patients With Diabetic Macular Edema

Conditions
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Diabetic Retinopathy

Intervention / Treatment
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* Drug: Squalamine Lactate Ophthalmic Solution 0.2%


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects will have clinically significant diabetic macular edema of ≥ 300 microns with central involvement using the Heidelberg or Cirrus machine Best corrected visual acuity of 20/32 to 20/320 inclusive in the study eye Adults ≥ 18 years of age with type 1 or 2 diabetes mellitus with diabetic macular edema Exclusion Criteria: History of vitreoretinal surgery in the study eye Panretinal laser photocoagulation or macular laser photocoagulation in the study eye within 3 months of screening Any prior laser in study eye Previous use of intraocular or periocular corticosteroids in the study eye within 6 months of screening Previous treatment with anti-angiogenic drugs in either eye within 3 months of screening Uncontrolled diabetes mellitus with HbA1c levels greater than 12 Ocular disorders in the study eye, other than diabetic macular edema, that my confound interpretation of study results

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Squalamine Solution BID 0.2%<br>Squalamine Lactate Ophthalmic Solution 0.2% administered twice a day for 52 weeks in combination with monthly intravitreal injections of ranibizumab 0.3mg from baseline through week 20 and ranibizumab as needed from week 24 through week 52 | Drug: Squalamine Lactate Ophthalmic Solution 0.2%<br>* Squalamine Lactate Ophthalmic Solution 0.2% eye drop to be administered to study eye either BID or QID for 52 weeks<br>* Other names: squalamine lactate;|
| Placebo Comparator: Vehicle Solution 0.2% BID<br>Vehicle Ophthalmic Solution 0.2% administered twice a day for 52 weeks in combination with monthly intravitreal injections of ranibizumab 0.3mg from baseline through week 20 and ranbizumab as needed from week 24 through week 52 | Drug: Squalamine Lactate Ophthalmic Solution 0.2%<br>* Squalamine Lactate Ophthalmic Solution 0.2% eye drop to be administered to study eye either BID or QID for 52 weeks<br>* Other names: squalamine lactate;|
| Experimental: Squalamine Solution 0.2% QID<br>Squalamine Lactate Ophthalmic Solution 0.2% administered four times a day for 52 weeks in combination with monthly intravitreal injections of ranibizumab 0.3mg from baseline through week 20 and ranibizumab as needed from week 24 through week 52 | Drug: Squalamine Lactate Ophthalmic Solution 0.2%<br>* Squalamine Lactate Ophthalmic Solution 0.2% eye drop to be administered to study eye either BID or QID for 52 weeks<br>* Other names: squalamine lactate;|
| Placebo Comparator: Vehicle Solution 0.2% QID<br>Vehicle Ophthalmic Solution 0.2% administered four times a day for 52 weeks in combination with monthly intravitreal injections of ranibizumab 0.3mg from baseline through week 20 and ranbizumab as needed from week 24 through week 52 | Drug: Squalamine Lactate Ophthalmic Solution 0.2%<br>* Squalamine Lactate Ophthalmic Solution 0.2% eye drop to be administered to study eye either BID or QID for 52 weeks<br>* Other names: squalamine lactate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To explore the effect of Squalamine Lactate eye drops on Best Corrected Visual Acuity in subjects with diabetic macular edema | Proportion of patients gaining at least 3,4 and 5 lines in best corrected visual acuity from baseline to week 24 | Mean change from baseline to Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the change in Central Retinal Thickness | Change in central retinal thickness at week 24 and at week 52 | Change at week 24 and at week 52 | 
| To assess need for rescue injections of Ranibizumab 0.3mg | To assess the number of rescue (as needed) ranibizumab re-treatments from week 24 through week 52 | Week 24 through week 52 | 
| To assess the safety and tolerability of Squalamine Eye Drops, measured by ophthalmic examination, the recording and evaluation of clinical AEs | Ongoing safety assessments will include ophthalmic examination, the recording and evaluation of clinical AEs | At week 24 and at Week 52 |