Clinical trial NCT01678963: Efficacy and Safety of Squalamine Lactate Eye Drops in Subjects With Neovascular (Wet) Age-related Macular Degeneration (AMD)
Official title: Phase II Study of the Efficacy and Safety of Squalamine Lactate Ophthalmic Formulation 0.2% BID in Subjects With Neovascular AMD.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Neovascular Age Related Macular Degeneration
Keywords: Neovascular AMD
Wet AMD
AMD
Age related macular degeneration
Lead sponsor: Ohr Pharmaceutical Inc.
Sponsor class: INDUSTRY
First posted: 2012-09-05
Enrollment: 142
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Need for continued concomitant therapy
timeFrame: 9 months
Secondary outcomes:
measure: Best Corrected Visual Acuity (BCVA)
timeFrame: 9 months
measure: Number of subjects with adverse events as a measure of safety and tolerability
timeFrame: 9 months
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Retina Associates SW
state: Arizona
city: Bakersfield
country: United States
facility: California Retinal Consultants
state: California
city: Beverly Hilss
country: United States
facility: Retina-Vitreous Associates
state: California
city: Golden
country: United States
facility: Colorado Retina
state: Colorado
city: Boynton Beach
country: United States
facility: Florida Eye Microsurgical Institute Inc.
state: Florida
city: Fort Myers
country: United States
facility: Retina Health Center
state: Florida
city: Indianapolis
country: United States
facility: Midwest Eye Institute
state: Indiana
city: Baltimore
country: United States
facility: Elman Retina
state: Maryland
city: Hagerstown
country: United States
facility: Cumberland Valley Retina Consultants
state: Maryland
city: Boston
country: United States
facility: Ophthalmic Consultants of Boston
state: Massachusetts
city: Grand Rapids
country: United States
facility: Vision Research Foundation
state: Michigan
city: Royal Oak
country: United States
facility: Vision Research Foundation
state: Michigan
city: Traverse City
country: United States
facility: Vision Research Foundation
state: Michigan
city: New Brunswick
country: United States
facility: Total Practice Management
state: New Jersey
city: New York
country: United States
facility: Macula Care
state: New York
city: Cleveland
country: United States
facility: Retina Associates of Cleveland
state: Ohio
city: Camp Hill
country: United States
facility: PA Retina
state: Pennsylvania
city: Nashville
country: United States
facility: TN Retina
state: Tennessee
city: San Antonio
country: United States
facility: Medical Center Ophthalmology Associates
state: Texas
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
Study officials:
References: