Study EvAluating Genotypes While Using Lucentis 2

Study Overview
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Brief Summary
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The purpose of the study is to investigate whether the efficacy of Lucentis treatment for exudative age-related macular degeneration is associated with VEGF and HTRA1 DNA polymorphisms

Detailed Description
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Age-related macular degeneration (AMD) is a progressive disease that causes irreversible visual impairment and blindness in nearly 50 million people globally. Although geographic atrophy and neovascularization represent the advanced forms of AMD, neovascular AMD is the more aggressive form and accounts for almost 90% of blindness from this disease. It is characterized by choroidal neovascularization (CNV) which is the development of abnormal blood vessels underneath the retina. Randomized clinical trials (MARINA, ANCHOR) have conclusively demonstrated that continued intravitreal therapy with Lucentis (ranibizumab) in patients with subfoveal CNV from AMD leads to stabilization of vision in over 90% of patients and improvement in vision in at least a third of the patients and has led to the approval of Lucentis for the treatment of neovascular AMD (see investigator brochure). This study could provide insight as to the reasons that some patients do not experience vision stabilization with Lucentis, and could possibly help physicians to determine which patients are the best candidates for receiving Lucentis. This is an open-label study of 100 treatment-naïve (study eye only) AMD patients treated on-label with intravitreally administered Lucentis. Consented, enrolled subjects will receive multiple open-label intravitreal injections of 0.5 mg ranibizumab administered monthly for the first 4 months, and then as needed for a total duration of 12 months. Their blood will be genotyped and sequenced for various SNPs on VEGF and HTRA1.

Official Title
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VEGF and HTRA1 DNA Polymorphisms in Neovascular AMD Pathogenesis and Response to Lucentis

Conditions
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Age-Related Macular Degeneration

Intervention / Treatment
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* Drug: Ranibizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ability to provide written informed consent and comply with the study assessments for the full duration of the study. Age > 50 years. Treatment naïve (study eye only) AMD patients that are determined to be candidates for ranbizumab. Visual acuity 20/32 to 20/230. Exclusion Criteria: Pregnancy Prior enrollment in the study Any other condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated Previous therapy in study eye for AMD or other retinal disease which may be used in the treatment of AMD. Any other condition that the investigator believes would pose a significant hazard to the subject if on-label ranibizumab were prescribed Any participation in another simultaneous medical investigation or trial for AMD *Concurrent eye disease in the study eye that could compromise visual acuity (e.g., diabetic retinopathy, advanced glaucoma)

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lucentis<br>Consented, enrolled subjects will receive multiple open-label intravitreally administered 0.5 mg ranibizumab administered monthly for the first 4 months, and then as needed for a total duration of 12 months. | Drug: Ranibizumab<br>* Intravitreal injections of 0.5 mg ranibizumab administered monthly for the first 4 months, and then as needed for a total duration of 12 months.<br>* Other names: Lucentis;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To Determine the Genotype at VEGF and HTRA1 SNPs of Patients Gaining ≥ 0 Letters of Visual Acuity in Response to Ranibizumab Treatment Over a 4 Month Period. |  | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To Determine the Genotype at VEGF and HTRA1 SNPs of Patients Who Lose Visual Acuity (Gain <0 Letters) at 4, 6 and 12 Months After Initial Treatment. |  | 5 years | 
| To Determine Whether Change in Retinal Thickness is Correlated With Genotype |  | 5 years | 
| To Determine the Mean Number of Injections Per Year Patients in the Study Require. |  | 5 years |