A Study Using Intravitreal Injections of a Small Interfering RNA in Patients With Age-Related Macular Degeneration

Study Overview
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Brief Summary
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This is a 24-month study to evaluate multiple doses of AGN211745 (previously known as Sirna-027) in treatment of subfoveal choroidal neovascularization associated with age-related macular degeneration

Conditions
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Choroid Neovascularization, Age-Related Macular Degeneration

Intervention / Treatment
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* Drug: AGN 211745
* Drug: AGN 211745
* Drug: AGN 211745
* Drug: Ranibizumab 500µg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 50 years or older with wet AMD as determined by an ophthalmologist decrease in visual acuity (20/40 to 20/640) in at least one eye Exclusion Criteria: Uncontrolled systemic disease History of heart attack or stroke within one year of study entry Symptomatic coronary artery disease Cataracts that interfere with vision

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AGN 211745 Solution 1000 ug<br>AGN 211745 Solution 1000 ug | Drug: AGN 211745<br>* AGN 211745 Solution 1000µg injection at Day 1, Month 1, Month 2<br>* Other names: Sirna-027;|
| Experimental: AGN 211745 Solution 300 ug<br>AGN 211745 Solution 300 ug | Drug: AGN 211745<br>* AGN 211745 Solution 300µg injections, Day 1, Month 1, Month 2<br>* Other names: Sirna-027;|
| Experimental: AGN 211745 Solution 100 ug<br>AGN 211745 Solution 100 ug | Drug: AGN 211745<br>* AGN 211745 Solution 100µg injections, Day 1, Month 1, Month 2<br>* Other names: Sirna-027;|
| Active Comparator: Ranibizumab 500 ug<br>Ranibizumab 500 ug | Drug: Ranibizumab 500µg<br>* Ranibizumab 500µg injections at Day 1, Month 1, Month 2<br>* Other names: Lucentis®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients With Improvement in Best Corrected Visual Acuity (BCVA) of 15 or More Letters at Month 3 | Percentage of patients with improvement in BCVA of 15 or more letters at Month 3. BCVA is measured using an eye chart and is reported as the number of letters read correctly (ranging from 0 to 100 letters). The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved. | Month 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lesion Size as Assessed by Fluorescein Angiography (FA) and Photography at Month 3 | Lesion size as assessed by FA and photography at month 3. FA is a technique for examining the circulation of the retina (and detecting any leakage) using a dye-tracing method. Photographs are taken with a specialized low-power microscope with an attached camera designed to photograph the interior of the eye, including the retina and optic disc. | Month 3 | 
| Foveal Thickness as Assessed by Optical Coherence Tomography (OCT) at Month 3 | Foveal thickness as assessed by OCT at month 3. The fovea is a part of the eye, located in the center of the macula region of the retina. OCT is a laser-based, noninvasive, diagnostic system providing high-resolution, three-dimensional images of the retina. The fovea is responsible for sharp central vision, which is necessary for reading or any activity where visual detail is of primary importance. Normal foveal thickness ranges from 175 to 250 microns. A foveal thickness greater than 250 microns represents worsening vision. | Month 3 | 
| Visual Functioning Questionnaire (VFQ) at Month 3 | Visual Functioning Questionnaire (VFQ) at Month 3. The VFQ includes 25 questions which assess visual impairment on functioning and specific aspects of health-related quality of life. Study terminated; data for this outcome measure were not analyzed. | Month 3 | 
| Time to Treatment With Standard of Care at Month 6 | Time to treatment with standard-of-care at month 6, defined as the number of days before the use of rescue therapy occurred. | Month 6 |