Prophylactic Ranibizumab for Exudative Age-related Macular Degeneration

Study Overview
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Brief Summary
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This study will determine whether quarterly injections of Ranibizumab may prevent eyes with dry age-related macular degeneration from progressing to wet age-related macular degeneration (AMD).

Detailed Description
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This is a multicenter, prospectively randomized, masked and controlled, interventional investigator sponsored phase I/II study of subjects with high-risk nonexudative age-related macular degeneration (AMD) treated with intravitreal ranibizumab quarterly for prophylaxis of conversion to exudative age-related macular degeneration. The objective of this study is to investigate the safety and efficacy of prophylactic anti-vascular endothelial growth factor (VEGF) therapy with ranibizumab to prevent the development of exudative AMD in eyes with high-risk nonexudative AMD. In addition, baseline characteristics of high-risk eyes (fundus features, optical coherence tomography (OCT) parameters and genetic profile) will be evaluated to determine their predictive value in conversion to exudative AMD. The effect of ranibizumab on the atrophic component of AMD will also be monitored.

Official Title
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Prophylactic Ranibizumab for Exudative Age-related Macular Degeneration (AMD) in Vulnerable Eyes With Nonexudative AMD Trial: A Multicenter, Prospectively Randomized, Masked and Controlled, Interventional Investigator Sponsored Phase I/II Study

Conditions
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Age-related Macular Degeneration

Intervention / Treatment
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* Drug: Ranibizumab 0.5mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult over 50 years old Able to sign informed consent and comply with the study protocol for the duration of two years Nonexudative age-related macular degeneration (AMD) in one eye (study eye) History of exudative AMD in one eye only (fellow eye) diagnosed within 5 years of study enrollment Exclusion Criteria: Participation in another simultaneous medical investigation or clinical trial Patient is pregnant, lactating, or premenopausal and not using adequate contraception Known serious allergies to ranibizumab, fluorescein dye, drugs for pupillary dilation, topical anesthetic, sterilizing solution (e.g. Betadine solution) Presence of ocular conditions with increased risk of choroidal neovascularization (CNVM) or pigment epithelial detachment (PED), including presumed ocular histoplasmosis syndrome (POHS), traumatic choroidal rupture, angioid streaks, pathologic myopia (spherical equivalent of ≥ -8 diopters or axial length of ≥ 25 mm), multifocal choroiditis, macular choroidal nevus, polypoidal choroidal vasculopathy (PCV), idiopathic central serous chorioretinopathy (ICSC), etc. History of vitrectomy in the study eye History of cataract surgery within 3 months of enrollment History of yttrium aluminum garnet (YAG) capsulotomy within 1 month of enrollment History of intraocular or periocular corticosteroid therapy within the past 90 days History of therapeutic radiation in the region of the study eye. Presence of media opacity that would preclude adequate examination and/or imaging Concurrent macular conditions that would affect the study parameters (epiretinal membrane, macular hole, macular edema) or require treatment within the duration of the study Any progressive ocular condition (uncontrolled glaucoma, diabetic retinopathy, uveitis) that may affect the visual acuity for the duration of the study Active ocular infection (i.e., bacterial, viral, parasitic, or fungal) in either eye at enrollment Presence of any advanced systemic condition that may hinder the patients participation and completion of the study Concurrent use of systemic anti-VEGF therapy

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Sham<br>Sham Injection | |
| Active Comparator: Quarterly Ranibizumab 0.5mg<br>Quarterly intravitreal injection of 0.5mg ranibizumab | Drug: Ranibizumab 0.5mg<br> <br> * Other names: Lucentis;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Development of exudative AMD | Development of choroidal neovascularization (conversion) defined by the presence of leakage on fluorescein angiography (FA) and fluid within or below the retina or below the retinal pigment epithelium seen on spectral-domain optical coherence tomography (SD-OCT) | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vision change | Change in best-corrected visual acuity (BCVA) from baseline at 12 and 24 months | 2 years | 
| Vision loss | Proportion of eyes losing < 5, 10, and 15 letters on EDTRS chart at 12 and 24 months | 2 years | 
| Number of injections | Number of injections required in eyes that convert from dry to wet AMD during the study period | 2 years | 
| Baseline predictive factors | Baseline demographic, genetic and ocular characteristics predictive of development of wet AMD | 2 years | 
| Development of geographic atrophy (GA) | Development of geographic atrophy (GA) as detected by fundus photography (FP) and/or fundus autofluorescence (AF). | 2 years | 
| Ocular adverse events | Incidence and severity of ocular adverse events, as identified by eye examination and imaging | 2 years | 
| Systemic adverse events | Incidence and severity of other adverse events, as identified by physical examination or subject reporting. | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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amd, non-exudative macular degeneration, exudative macular degeneration, age-related macular degeneration, ranibizumab, anti-VEGF