Safety and Efficacy of Brimonidine Intravitreal Implant in Patients With Geographic Atrophy Due to Age-related Macular Degeneration (AMD)

Study Overview
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Brief Summary
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Stage 1 is a patient-masked, dose-escalation, safety evaluation of brimonidine intravitreal implant. Patients will receive implant in one eye and sham treatment (meaning no treatment) in the fellow eye. Stage 2 will begin after 1 month of safety has been evaluated for Stage 1. Stage 2 is a randomized, double-masked, dose-response, sham-controlled evaluation of the safety and efficacy of brimonidine intravitreal implant in patients with geographic atrophy from age-related macular degeneration. Patients will be followed for up to 2 years.

Official Title
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Safety and Efficacy of Brimonidine Intravitreal Implant in Patients With Geographic Atrophy Due to AMD

Conditions
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Macular Degeneration

Intervention / Treatment
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* Drug: 400 µg Brimonidine Tartrate Implant
* Drug: 200 µg Brimonidine Tartrate Implant
* Other: Sham (no implant)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Geographic atrophy in both eyes due to age-related macular degeneration Visual acuity between 20/40 to 20/320 Exclusion Criteria: Known allergy to brimonidine Uncontrolled systemic disease or infection of the eye Recent eye surgery or injections in the eye Female patients who are pregnant, nursing or planning a pregnancy

Ages Eligible for Study
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Minimum Age: 50 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 |
| --- | --- |
| Other: 400 µg Brimonidine Tartrate Implant Stage 1<br>Stage 1: 400 µg brimonidine tartrate implant in the study eye and sham in the fellow eye on Day 1 and Month 6. | Drug: 400 µg Brimonidine Tartrate Implant<br>* 400 µg brimonidine tartrate implant in the study eye on Day 1 and Month 6.<br>* Other names: Brimonidine Tartrate PS DDS®;Other: Sham (no implant)<br>* Sham in one or both eyes on Day 1 and Month 6.<br>|
| Other: 200 µg Brimonidine Tartrate Implant Stage 1<br>Stage 1: 200 µg brimonidine tartrate implant in the study eye and sham in the fellow eye on Day 1 and Month 6. | Drug: 200 µg Brimonidine Tartrate Implant<br>* 200 µg brimonidine tartrate implant in the study eye on Day 1 and Month 6.<br>* Other names: Brimonidine Tartrate PS DDS®;Other: Sham (no implant)<br>* Sham in one or both eyes on Day 1 and Month 6.<br>|
| Other: 400 µg Brimonidine Tartrate Implant Stage 2<br>Stage 2: 400 µg brimonidine tartrate implant in the study eye and sham in the fellow eye on Day 1 and Month 6. | Drug: 400 µg Brimonidine Tartrate Implant<br>* 400 µg brimonidine tartrate implant in the study eye on Day 1 and Month 6.<br>* Other names: Brimonidine Tartrate PS DDS®;Other: Sham (no implant)<br>* Sham in one or both eyes on Day 1 and Month 6.<br>|
| Other: 200 µg Brimonidine Tartrate Implant Stage 2<br>Stage 2: 200 µg brimonidine tartrate implant in the study eye and sham in the fellow eye on Day 1 and Month 6. | Drug: 200 µg Brimonidine Tartrate Implant<br>* 200 µg brimonidine tartrate implant in the study eye on Day 1 and Month 6.<br>* Other names: Brimonidine Tartrate PS DDS®;Other: Sham (no implant)<br>* Sham in one or both eyes on Day 1 and Month 6.<br>|
| Sham Comparator: Sham (no implant) Stage 2<br>Stage 2: sham in both eyes on Day 1 and Month 6. | Other: Sham (no implant)<br>* Sham in one or both eyes on Day 1 and Month 6.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Size of Geographic Atrophy Lesion Area in the Study Eye | Change from baseline in size of geographic atrophy lesion area in the study eye is based on fundus photography as read by an independent Reading Center. Photographs are taken with a specialized microscope with an attached camera to photograph the interior of the eye, including the retina and optic disc. A positive change from baseline indicates an increase in size of geographic atrophy lesion area (worsening; disease progression). Data are reported in disc area where 1 disc area = 1.767 millimeters squared (mm^2). | Baseline, Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Size of Geographic Atrophy Lesion Area in the Study Eye | Change from baseline in size of geographic atrophy lesion area in the study eye is based on fundus photography as read by an independent Reading Center. Photographs are taken with a specialized microscope with an attached camera to photograph the interior of the eye, including the retina and optic disc. A positive change from baseline indicates an increase in size of geographic atrophy lesion area (worsening; disease progression). Data are reported in disc area where 1 disc area = 1.767 millimeters squared (mm^2). | Baseline, Month 3, Month 6, Month 9, Month 18, Month 24 | 
| Change From Baseline in Best Corrected Visual Acuity (BCVA) in the Study Eye | BCVA is measured using an eye chart and is reported as the number of letters read correctly (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). A positive change from baseline indicates an improvement and a negative change from baseline indicates a worsening. | Baseline, 24 Months | 
| Change From Baseline in Contrast Sensitivity in the Study Eye | Change from baseline in contrast sensitivity in the study eye is measured using a Pelli-Robson contrast sensitivity chart at 1 meter. The contrast sensitivity chart contains letters that are darkest at the top and then get progressively lighter. Scores range from 0 to 48 and are based on the number of letters read correctly. A negative change from baseline indicates a worsening in contrast sensitivity and a positive change from baseline indicates an improvement. | Baseline, 24 Months | 
| Change From Baseline in Reading Speed in the Study Eye | Change from baseline in reading speed in the study eye is assessed using modified Bailey-Lovie word charts. Patients read the chart for 2 minutes and the numbers of words read correctly per minute are totaled. An increase in the number of words read correctly indicates an improvement and a decrease in the number of words read correctly indicates a worsening. | Baseline, 24 Months |