A Dose Escalation Trial of an Intravitreal Injection of Sirna-027 in Patients With Subfoveal Choroidal Neovascularization (CNV) Secondary to Age-Related Macular Degeneration (AMD)

Study Overview
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Brief Summary
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The purpose of this study will be to assess the safety and tolerability and dose-limiting toxicity of a single intravitreal injection of Sirna-027 (AGN211745) and to assess the anatomical changes in the retina, changes in CNV, and changes in visual acuity. Escalation to the next dose cohort will be completed following minimum of 2 weeks follow-up. Patients will be monitored intensively for three months, and then followed-up for safety up to 24 months post-injection.

Conditions
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Age-Related Macular Degeneration, Choroidal Neovascularization

Intervention / Treatment
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* Drug: AGN211745
* Drug: AGN211745
* Drug: AGN211745
* Drug: AGN211745
* Drug: AGN211745
* Drug: AGN211745


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Active AMD with Subfoveal CNV (classic and/or occult CNV) CNV lesion thickness >/= 250um by OCT assessment Visual acuity in study eye of </= 20/100 but not worse than 20/800 Not eligible for or refused standard treatment Exclusion Criteria: Females of childbearing potential Other causes of CNV including pathologic myopia, the ocular histoplasmosis syndrome, angioid streaks, choroidal rupture and multifocal choroiditis Any intraocular surgery or treatment of AMD with Visudyne within 3 months of study entry CNV lesion >/= 12 MPS disc area

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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Single intravitreal injection | Drug: AGN211745<br>* 100microgram single intravitreal injection<br>* Other names: Sirna-027;|
| Experimental: 2<br>Single intravitreal injection | Drug: AGN211745<br>* 200microgram single intravitreal injection<br>* Other names: Sirna-027;|
| Experimental: 3<br>Single intravitreal injection | Drug: AGN211745<br>* 400microgram single intravitreal injection<br>* Other names: Sirna-027;|
| Experimental: 4<br>Single intravitreal injection | Drug: AGN211745<br>* 800microgram single intravitreal injection<br>* Other names: Sirna-027;|
| Experimental: 5<br>Single intravitreal injection | Drug: AGN211745<br>* 1200microgram single intravitreal injection<br>* Other names: Sirna-027;|
| Experimental: 6<br>Single intravitreal injection | Drug: AGN211745<br>* 1600microgram single intravitreal injection<br>* Other names: Sirna-027;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events |  | Time frame 3 months: Baseline/Day 1, Day 2, Day 7, Day 14, Day 28, Day 56, Day 84 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual Acuity using the Diabetic Retinopathy Study chart |  | Time frame 24 months: Screening, Day 1, Day 2, Day 7, Day 14, Day 28, Day 56, Day 84, Month 6, Month 9, Month 12, Month 18, Month 24 | 
| IOP |  | Time frame 24 months: Screening, Day 1, Day 2, Day 7, Day 14, Day 28, Day 56, Day 84, Month 6, Month 9, Month 12, Month 18, Month 24 | 
| OCT |  | Time frame 3 months: Screening, Day 7, Day 14, Day 28, Day 56, Day 84 | 
| Fluorescein Angiography (FA) |  | Time frame 24 months (Screening, Day 7, Day 14, Day 28, Day 84 and Month 24) |