OT-551 Antioxidant Eye Drops to Treat Geographic Atrophy in Age-Related Macular Degeneration - Full Text View

Sponsored by:	National Eye Institute (NEI)
Information provided by:	National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:	NCT00306488

Purpose

Age-related Macular Degeneration (AMD), the leading cause of blindness in people over age 55 in the U.S. is a heterogeneous clinical entity in which retinal degeneration occurs predominantly in the macula in the context of aging and leads to impairment primarily of central visual acuity. AMD occurs in two general forms, one of which involves subchoroidal neovascularization with subsequent formation of a disciform scar. A second form, and the subject of this study, is termed "dry" or atrophic macular degeneration and involves a constellation of clinical features that can include drusen, pigment clumping and/or retinal pigment epithelium (RPE) dropout, and geographic atrophy. Geographic atrophy can begin as a thinning of the RPE with involvement of the underlying choriocapillaris and lead subsequently to an atrophic change in the macula. The only therapy for persons with atrophic AMD is an oral supplement containing high doses of antioxidants and zinc, which was tested by the National Eye Institute (NEI) in a large, multicenter, double-masked, placebo-controlled clinical trial with average participant follow-up of about 6 years. This antioxidant therapy was shown to modestly retard the progression of dry AMD from an intermediate stage to the advanced stages and confirmed the benefit of therapy in this disease.

Othera Pharmaceuticals' Othera (OT)-551 antioxidant eye drop has the potential for chronic treatment of the dry form of age-related macular degeneration. This pilot study of up to 10 eye drop tolerant participants with bilateral geographic atrophy is designed to characterize the effect of 0.45% concentration of OT-551 eye drops given 3 times a day on the progression of geographic atrophy area over a two-year period. Participants will have one eye randomized to receive the eye drop and the fellow eye will be observed only....

Condition	Intervention	Phase
Bilateral Geographic Atrophy Age-Related Macular Degeneration AMD	Drug: OT - 551	Phase II

Genetics Home Reference related topics: X-linked juvenile retinoschisis

MedlinePlus related topics: Antioxidants Macular Degeneration

Drug Information available for: Tetrahydrozoline Tetrahydrozoline hydrochloride OT-551

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment
Official Title:	A Phase II Study of OT-551 Antioxidant Eye Drop in Participants With Bilateral Geographic Atrophy Associated With Age-Related Macular Degeneration

Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:

The chance in best-corrected visual acuity from baseline to yr 2 for all participants. Visual acuity will be measured at 4 meters using the ETDRS method. This assessment will be made over multiple time points throughout the study.@@@ [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Absolute percent change from baseline in area of geographic atrophy (GA) in each eye as graded on digitized images of color fundus photographs and autofluorescence. Progression to advanced neovascular AMD based on the reading centers assessment [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment:	50
Study Start Date:	March 2006

Intervention Details:

N/A

Detailed Description:

Age-related macular Degeneration (AMD), the leading cause of blindness in people over age 55 in the U.S. is a heterogeneous clinical entity in which retinal degeneration occurs predominantly in the macula in the context of aging and leads to impairment primarily of central visual acuity. AMD occurs in two general forms, one of which involves subchoroidal neovascularization with subsequent formation of a disciform scar. A second form, and the subject of this study, is termed "dry" or atrophic macular degeneration and involves a constellation of clinical features that can include drusen, pigment clumping and/or retinal pigment epithelium (RPE) dropout, and geographic atrophy. Geographic atrophy can begin as a thinning of the RPE with involvement of the underlying choriocapillaris and lead subsequently to an atrophic change in the macula. The only therapy for persons with atrophic AMD is an oral supplement containing high doses of antioxidants and zinc, which was tested by the National Eye Institute (NEI) in a large, multicenter, double-masked, placebo-controlled clinical trial with average participant follow-up of about 6 years. This antioxidant therapy was shown to modestly retard the progression of dry AMD from an intermediate stage to the advanced stages and demonstrated the benefit of antioxidant therapy in this disease.

In this study, we will evaluate Othera Pharmaceuticals' OT-551 antioxidant eye drop for chronic treatment of the dry form of AMD. This single-center, open-label, study of up to 10 participants with bilateral geographic atrophy is designed to characterize the safety of 0.45 percent concentration of OT-551 eye drops, given 3 times a day, on participants with geographic atrophy area for up to three years. Participants will have one eye randomized to receive the eye drop and the fellow eye will be observed.

Eligibility

Ages Eligible for Study:	60 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

INCLUSION CRITERIA:
1. Participant must understand and sign the protocol's informed consent document (if the participant's vision is impaired to the point where it is not possible to read the informed consent document, the informed consent document will be read in its entirety to the participant).
2. Participant must be able to administer the eye drops or have a caretaker administer the eye drops.
3. Participant must have geographic atrophy (GA) present in both eyes compatible with age-related macular degeneration (AMD). GA is defined as one or more well-defined, usually more or less circular patches of partial or complete depigmentation of the RPE, typically with exposure of underlying choroidal blood vessels. Even if much of the RPE appears to be preserved and large choroidal vessels are not visible, a roundish patch of RPE partial depigmentation may still be classified as early GA. The GA in each eye must be able to be photographed in their entirety and not contiguous with any areas of peripapillary atropy, which can complicate area measurements.
4. Participant must have a steady fixation in the study eye in the foveal or parafoveal area and media clear enough for good quality photographs.
5. Female participants of child bearing potential (those who are not post-menopausal or surgically sterile) may participate if they are not lactating and if they agree to adequate birth control methods.

EXCLUSION CRITERIA:

Participant is less than 60 years of age (to minimize fundus changes from causes other than AMD).
Participant is in another investigational study and actively receiving study therapy.
Participant is unable to comply with study procedures or follow-up visits.
Participant has evidence of ocular disease other than AMD in either eye that may confound the outcome of the study (e.g., diabetic retinopathy, uveitis, etc.).
Participant has a chronic requirement (e.g., greater than or equal to 4 weeks at a time) for ocular medications for diseases, that in the judgment of the examining physician, are vision threatening or may affect the primary outcome (artificial tears are permitted).
Participant has evidence of pseudovitelliform macular degeneration in either eye.
Participant with evidence of vitreo-retinal traction maculopathy in either eye.
Participant has a history of laser, photodynamic therapy (PDT), intravitreal injection of any agent (e.g., anti-VEGF, triamcinolone, etc.), or any previous treatment for AMD other than AREDS or equivalent supplement formulation in the study eye.
Participant has had a vitrectomy, penetrating keratoplasty, trabeculectomy or trabeculoplasty.
Participant has undergone lens removal in the last 3 months.
Participant is on chemotherapy.
Participant is on ocular or systemic medications known to be toxic to the lens, retina, or optic nerve.
Participant with a history of malignancy that would compromise the 2-year study survival.
Participant with a history of ocular Herpes simplex virus.
Participant with a history of or demonstration of allergy to benzakonium chloride, a preservative agent used in the eye drop.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00306488

Locations

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892

Sponsors and Collaborators

National Eye Institute (NEI)

More Information

NIH Clinical Center Detailed Web Page This link exits the ClinicalTrials.gov site

Publications:

[No authors listed] A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8. Arch Ophthalmol. 2001 Oct;119(10):1417-36.

Klein R, Klein BE, Jensen SC, Meuer SM. The five-year incidence and progression of age-related maculopathy: the Beaver Dam Eye Study. Ophthalmology. 1997 Jan;104(1):7-21.

Klein R, Klein BE, Linton KL. Prevalence of age-related maculopathy. The Beaver Dam Eye Study. Ophthalmology. 1992 Jun;99(6):933-43.

Responsible Party:	( NEI )
Study ID Numbers:	060116, 06-EI-0116
Study First Received:	March 22, 2006
Last Updated:	December 23, 2008
ClinicalTrials.gov Identifier:	NCT00306488
Health Authority:	United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):

Retinal Pigment Epithelium
Dynamic Light Scattering (DLS)
Visual Acuity Decrease
Intra-ocular Pressure

Autofluorescence of Retina
Age-Related Macular Degeneration
AMD

Study placed in the following topic categories:

Pathological Conditions, Anatomical
Eye Diseases
Retinal Degeneration
Macular Degeneration

Atrophy
Tetrahydrozoline
Retinal Diseases
Retinal degeneration

ClinicalTrials.gov processed this record on January 14, 2009