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

Primary Purpose

Geographic Atrophy, Age-Related Macular Degeneration, AMD

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
OT-551 antioxidant eye drop
Sponsored by
National Institutes of Health Clinical Center (CC)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Geographic Atrophy focused on measuring Retinal Pigment Epithelium, Dynamic Light Scattering (DLS), Visual Acuity Decrease, Intra-ocular Pressure, Autofluorescence of Retina, Age-Related Macular Degeneration, AMD

Eligibility Criteria

60 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria 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). Participant must be able to administer the eye drops or have a caretaker administer the eye drops. 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 round-ish 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 atrophy, which can complicate area measurements. Participant must have a steady fixation in the study eye in the foveal or parafoveal area and media clear enough for good quality photographs. 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. 4.5 Exclusion Criteria Participant is > 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., ≥ four 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 that may confound the outcome of the study in either eye. Participant with evidence of vitreo-retinal traction maculopathy that may confound the outcome of the study 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 three 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.

Sites / Locations

  • National Institutes of Health Clinical Center, 9000 Rockville Pike

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

OT-551 antioxidant eye drop

Arm Description

The fellow eye was treated with OT-551 antioxidant eye drops over the course of the study.

Outcomes

Primary Outcome Measures

The Change in Best-corrected Visual Acuity (BCVA) From Baseline to Year 2 for All Participants.
Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. This acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters the Snellen measurement is 20/20.

Secondary Outcome Measures

The Change in Geographic Atrophy (GA), as Measured on Fundus Autofluorescence Imaging Using a Confocal Scanning Ophthalmoscope (HRA FAF) From Baseline to Year 2.
Geographic Atrophy (GA), or the death of photoreceptors and surrounding cells in the retina, is a common condition in patients with Age-Related Macular Degeneration (AMD). The death of these photoreceptors results in lesions that cause vision loss. The amount of GA is measured from images produced via a non-invasive technique called Fundus Autofluorescence Imaging, which uses a Confocal Scanning Ophthalmoscope to detect the naturally-fluorescing lipofuscin (the waste that is left behind by dead photoreceptors and digested by surrounding cells) that is prevalent at the border of the lesion.
The Change in GA, as Measured on Stereoscopic Color Fundus Photography (CFP) From Baseline to Year 2.
GA was also measured using Stereoscopic Color Fundus Photography (CFP), which produces color images of the inside of the eye.
The Change in Contrast Sensitivity as Measured by the Pelli-Robson Chart From Baseline to Year 2.
The Pelli-Robson Chart is comprised of 10 groups of 3 large letters with levels of contrast ranging from 100% (black against white) to 1% (very light gray against white). Each eye is assigned a score based on the contrast of the last group in which two or three letters were correctly read. A score of 2 log units, which represents a normal sensitivity contrast, indicates that the eye was able to detect two of the three letters with a contrast of 1 percent (contrast sensitivity = 100 percent or log 2).
Number of Participants With an Increase in the Number of Scotomatous Points Between Study and Fellow Eyes From Baseline to Year 2.
Scotomatous points are testing points on microperimetry examination that are centered on the macula and report a lack of retinal sensitivity within the range tested.
The Change in Total Drusen Area From Baseline to Year 2.

Full Information

First Posted
March 22, 2006
Last Updated
July 6, 2020
Sponsor
National Institutes of Health Clinical Center (CC)
Collaborators
National Eye Institute (NEI), Othera Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT00306488
Brief Title
OT-551 Antioxidant Eye Drops to Treat Geographic Atrophy in Age-Related Macular Degeneration
Official Title
A Phase II Study of OT-551 Antioxidant Eye Drop in Participants With Bilateral Geographic Atrophy Associated With Age-Related Macular Degeneration
Study Type
Interventional

2. Study Status

Record Verification Date
August 2011
Overall Recruitment Status
Completed
Study Start Date
March 2006 (undefined)
Primary Completion Date
March 2010 (Actual)
Study Completion Date
March 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institutes of Health Clinical Center (CC)
Collaborators
National Eye Institute (NEI), Othera Pharmaceuticals

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Geographic Atrophy, Age-Related Macular Degeneration, AMD
Keywords
Retinal Pigment Epithelium, Dynamic Light Scattering (DLS), Visual Acuity Decrease, Intra-ocular Pressure, Autofluorescence of Retina, Age-Related Macular Degeneration, AMD

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
11 (Actual)

8. Arms, Groups, and Interventions

Arm Title
OT-551 antioxidant eye drop
Arm Type
Experimental
Arm Description
The fellow eye was treated with OT-551 antioxidant eye drops over the course of the study.
Intervention Type
Drug
Intervention Name(s)
OT-551 antioxidant eye drop
Intervention Description
0.45% concentration of OT-551 eye drops were given three times a day on participants with geographic atrophy area for up to three years. Participants had one eye randomized to receive the eye drop and the fellow eye was observed.
Primary Outcome Measure Information:
Title
The Change in Best-corrected Visual Acuity (BCVA) From Baseline to Year 2 for All Participants.
Description
Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. This acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters the Snellen measurement is 20/20.
Time Frame
2 years
Secondary Outcome Measure Information:
Title
The Change in Geographic Atrophy (GA), as Measured on Fundus Autofluorescence Imaging Using a Confocal Scanning Ophthalmoscope (HRA FAF) From Baseline to Year 2.
Description
Geographic Atrophy (GA), or the death of photoreceptors and surrounding cells in the retina, is a common condition in patients with Age-Related Macular Degeneration (AMD). The death of these photoreceptors results in lesions that cause vision loss. The amount of GA is measured from images produced via a non-invasive technique called Fundus Autofluorescence Imaging, which uses a Confocal Scanning Ophthalmoscope to detect the naturally-fluorescing lipofuscin (the waste that is left behind by dead photoreceptors and digested by surrounding cells) that is prevalent at the border of the lesion.
Time Frame
2 years
Title
The Change in GA, as Measured on Stereoscopic Color Fundus Photography (CFP) From Baseline to Year 2.
Description
GA was also measured using Stereoscopic Color Fundus Photography (CFP), which produces color images of the inside of the eye.
Time Frame
2 years
Title
The Change in Contrast Sensitivity as Measured by the Pelli-Robson Chart From Baseline to Year 2.
Description
The Pelli-Robson Chart is comprised of 10 groups of 3 large letters with levels of contrast ranging from 100% (black against white) to 1% (very light gray against white). Each eye is assigned a score based on the contrast of the last group in which two or three letters were correctly read. A score of 2 log units, which represents a normal sensitivity contrast, indicates that the eye was able to detect two of the three letters with a contrast of 1 percent (contrast sensitivity = 100 percent or log 2).
Time Frame
2 years
Title
Number of Participants With an Increase in the Number of Scotomatous Points Between Study and Fellow Eyes From Baseline to Year 2.
Description
Scotomatous points are testing points on microperimetry examination that are centered on the macula and report a lack of retinal sensitivity within the range tested.
Time Frame
2 years
Title
The Change in Total Drusen Area From Baseline to Year 2.
Time Frame
Baseline, 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria 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). Participant must be able to administer the eye drops or have a caretaker administer the eye drops. 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 round-ish 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 atrophy, which can complicate area measurements. Participant must have a steady fixation in the study eye in the foveal or parafoveal area and media clear enough for good quality photographs. 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. 4.5 Exclusion Criteria Participant is > 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., ≥ four 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 that may confound the outcome of the study in either eye. Participant with evidence of vitreo-retinal traction maculopathy that may confound the outcome of the study 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 three 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Wai Wong, MD, PhD
Organizational Affiliation
National Eye Institute (NEI)
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Institutes of Health Clinical Center, 9000 Rockville Pike
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
11594942
Citation
Age-Related Eye Disease Study Research Group. 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. doi: 10.1001/archopht.119.10.1417. Erratum In: Arch Ophthalmol. 2008 Sep;126(9):1251.
Results Reference
background
PubMed Identifier
9022098
Citation
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. doi: 10.1016/s0161-6420(97)30368-6.
Results Reference
background
PubMed Identifier
1630784
Citation
Klein R, Klein BE, Linton KL. Prevalence of age-related maculopathy. The Beaver Dam Eye Study. Ophthalmology. 1992 Jun;99(6):933-43. doi: 10.1016/s0161-6420(92)31871-8.
Results Reference
background
PubMed Identifier
20926818
Citation
Meleth AD, Mettu P, Agron E, Chew EY, Sadda SR, Ferris FL, Wong WT. Changes in retinal sensitivity in geographic atrophy progression as measured by microperimetry. Invest Ophthalmol Vis Sci. 2011 Feb 28;52(2):1119-26. doi: 10.1167/iovs.10-6075. Print 2011 Feb.
Results Reference
derived
PubMed Identifier
20574018
Citation
Wong WT, Kam W, Cunningham D, Harrington M, Hammel K, Meyerle CB, Cukras C, Chew EY, Sadda SR, Ferris FL. Treatment of geographic atrophy by the topical administration of OT-551: results of a phase II clinical trial. Invest Ophthalmol Vis Sci. 2010 Dec;51(12):6131-9. doi: 10.1167/iovs.10-5637. Epub 2010 Jun 23.
Results Reference
derived

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

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