Efficacy and Safety of Squalamine Lactate Eye Drops in Subjects With Neovascular (Wet) Age-related Macular Degeneration (AMD)

Phase II Study of the Efficacy and Safety of Squalamine Lactate Ophthalmic Formulation 0.2% BID in Subjects With Neovascular AMD.

The purpose of this study is to evaluate the safety and efficacy of topical ophthalmic squalamine lactate eye drops in treating patients with neovascular age-related macular degeneration (wet AMD), a degenerative retinal eye disease that causes a progressive, irreversible, severe loss of central vision.

Study Overview

• Status: Completed
• Conditions: Neovascular Age Related Macular Degeneration
• Intervention / Treatment: Drug: Squalamine lactate; Drug: Vehicle control

Detailed Description

Age-related macular degeneration (AMD) is a degenerative retinal eye disease that causes a progressive loss of central vision. AMD is the leading cause of legal blindness among adults age 50 or older in the Western world and affects 25-30 million people globally. This number is expected to triple over the next 25 years. Central vision loss from AMD is caused by the degeneration of light-sensing cells in the macula called photoreceptors. The macula, the central portion of the retina, is responsible for perceiving fine visual detail. As photoreceptors begin to degenerate, so does the individual's central vision. The extent of vision loss varies widely and is related to the type of AMD, its severity and other individual characteristics.

AMD presents itself in two different forms - a "dry" form and the more severe "wet" form. Dry AMD, the more common and milder form of AMD, accounts for 85% to 90% of all cases. It results in varying forms of sight loss and may or may not eventually develop into the wet form. Although the wet form of AMD accounts for only 10% to 15% of all AMD, the chance for severe sight loss is much greater. Wet AMD is responsible for 90% of severe vision loss associated with AMD. Approximately 500,000 new cases of wet AMD are diagnosed annually worldwide. In North America alone, approximately 200,000 new cases of wet AMD are diagnosed each year.

Squalamine lactate has been found to be an inhibitor of new blood vessel formation (angiogenesis) induced by VEGF, PDGF or bFGF. Since angiogenesis is implicated in the growth and maintenance of choroidal neovascularization, squalamine lactate is potentially an attractive development candidate in the treatment of age-related macular degeneration (AMD), in which blood vessel proliferation has a role.

• Study Type: Interventional
• Enrollment (Actual): 142
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85710
      • Retina Associates SW
  • California
    • Bakersfield, California, United States, 93309
      • California Retinal Consultants
    • Beverly Hilss, California, United States, 90211
      • Retina-Vitreous Associates
  • Colorado
    • Golden, Colorado, United States, 80401
      • Colorado Retina
  • Florida
    • Boynton Beach, Florida, United States, 33426
      • Florida Eye Microsurgical Institute Inc.
    • Fort Myers, Florida, United States, 33907
      • Retina Health Center
  • Indiana
    • Indianapolis, Indiana, United States, 46290
      • Midwest Eye Institute
  • Maryland
    • Baltimore, Maryland, United States, 21237
      • Elman Retina
    • Hagerstown, Maryland, United States, 21740
      • Cumberland Valley Retina Consultants
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Ophthalmic Consultants of Boston
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • Vision Research Foundation
    • Royal Oak, Michigan, United States, 48073
      • Vision Research Foundation
    • Traverse City, Michigan, United States, 49686
      • Vision Research Foundation
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Total Practice Management
  • New York
    • New York, New York, United States, 10021
      • Macula Care
  • Ohio
    • Cleveland, Ohio, United States, 44122
      • Retina Associates of Cleveland
  • Pennsylvania
    • Camp Hill, Pennsylvania, United States, 17011
      • PA Retina
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • TN Retina
  • Texas
    • San Antonio, Texas, United States, 78240
      • Medical Center Ophthalmology Associates
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • University of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• ≥50 years of age, male or female

• Have the following criteria in the study eye:

  • A diagnosis of choroidal neovascularization secondary to AMD with total lesion area ≤ 12 disc areas with CNV affecting at least 50% of the total lesion area, in at least one eye confirmed by fluorescein angiography (via the reading center)
  • Central Retinal Thickness (SD- OCT central 1 mm) of ≥ 300 um
  • Presence of sub-retinal fluid or cystoid edema on OCT. Pigment epithelial detachments without subretinal fluid or cystoid edema will be excluded
  • BCVA 20/40 to 20/230 (25 to 70 letters ETDRS)
  • If both eyes qualify the eye with the greater CRT will be the study eye. If both equal the right eye will be selected as the study eye.
• Female subjects must be 1-year postmenopausal or surgically sterilized, Women of childbearing potential must have a negative urine pregnancy test and must use an acceptable method of contraception throughout the study.
• Be willing and able to provide signed informed consent prior to participation in any study-related procedures.

Exclusion Criteria:

• Neovascularization secondary to any condition other than AMD in the study eye.
• Blood occupying greater than 50% of the AMD lesion. Blood underlying the fovea.
• Prior treatment in the study eye with bevacizumab, ranibizumab, aflibercept, PDT, submacular surgery, any antiangiogenic drug.
• Confounding ocular conditions in the study eye which will affect interpretation of OCT, VA or assessment of macular appearance eg: cataract.
• Subjects with VA worse than 20/200 (less than 34 letters) in the fellow (non-study) eye.
• Fibrosis or atrophy, retinal epithelial tear in the center of the fovea in the study eye or any condition preventing VA improvement.
• Prior ocular surgery in the study eye (Vitrectomy, scleral buckle, or glaucoma filter/shunt). Cataract surgery more than 3 months prior to enrollment is allowed so long as a posterior chamber intraocular lens is in place.
• Wearing contact lenses.
• Concomitant therapy with any drug that may affect VA, meds that may be toxic to the lens/retina or optic nerve.
• Current ocular or periocular infection in the study eye.
• Hypersensitivity to Lucentis.
• Hypersensitivity to squalamine or any component of the ophthalmic formulation
• Presence of a life threatening disease or currently on treatment for a malignancy.
• Currently on chemotherapy.
• Currently on systemic steroids.
• Pregnant or lactating.
• Investigational product use of any kind in the previous 30 days.
• Subjects for whom attendance for monthly examinations may be unreliable eg: dependent on an elderly caregiver.
• Glaucoma in the study eye (glaucomatous visual field defect and receiving treatment).
• Myocardial infarction or cerebrovascular accident or transient ischemic attacks (TIA) within the past 6 months.
• Clinical evidence of diabetic retinopathy or diabetic macular edema in the study eye.
• Uncontrolled hypertension (Diastolic BP >105 mmHg) in spite of antihypertensive medications.
• Subjects known to have HIV.
• A history of drug or alcohol abuse.
• Subjects unable to administer eye drops reliably.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Squalamine; Squalamine eye drop 0.2%	Drug: Squalamine lactate; Ophthalmic solution 0.2%
Placebo Comparator: Vehicle Control; Eye drop vehicle control	Drug: Vehicle control; Ophthalmic solution vehicle control

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Need for continued concomitant therapy	Lucentis (ranibizumab) is the current standard of care for the treatment of wet AMD. All patients will receive an initial injection of Lucentis prior to randomization and then be evaluated monthly for their need for further Lucentis injections using protocol defined retreatment criteria.	9 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best Corrected Visual Acuity (BCVA)	Evaluation of the effect of treatment on visual function (BCVA) as measured using the EDTRS chart measured at an initial distance of 4 meters.	9 months
Number of subjects with adverse events as a measure of safety and tolerability	The frequency, severity, seriousness of all adverse events including their relationship to study drug and effect on discontinuation from the study will be monitored, recorded and analysed.	9 months

Collaborators and Investigators

• Sponsor: Ohr Pharmaceutical Inc.

Study record dates

Study Major Dates

• Study Start: November 1, 2012
• Primary Completion (Actual): March 1, 2015
• Study Completion (Actual): March 1, 2015

Study Registration Dates

• First Submitted: August 27, 2012
• First Submitted That Met QC Criteria: August 30, 2012
• First Posted (Estimate): September 5, 2012

Study Record Updates

• Last Update Posted (Estimate): June 12, 2015
• Last Update Submitted That Met QC Criteria: June 11, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Keywords: AMD; Wet AMD; Neovascular AMD; Age related macular degeneration
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Physiological Effects of Drugs; Anti-Infective Agents; Antineoplastic Agents; Protective Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Anti-Bacterial Agents; Anticarcinogenic Agents; Squalamine
• Other Study ID Numbers: OHR-002