An Extension Study to Evaluate the Safety and Tolerability of Ranibizumab in Subjects With Choroidal Neovascularization Secondary to AMD or Macular Edema Secondary to RVO

Study Overview
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Brief Summary
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This was an open-label, multicenter, extension study of intravitreally administered ranibizumab in two cohorts. The first cohort (reported here) enrolled patients with primary or recurrent Choroidal Neovascularization (CNV) secondary to Age-Related Macular Degeneration (AMD) who completed the treatment phase of a Genentech sponsored study (FVF2598g (NCT00056836), FVF2587g (NCT00061594), or FVF2428g (NCT00056823)). The second cohort enrolled patients with macular edema secondary to Retinal Vein Occlusion (RVO) who completed the 6-month treatment and 6-month observation phases (12 months total) of a Genentech sponsored study (FVF4165g (NCT00486018) or FVF4166g (NCT00485836)). The results of the second cohort are reported separately (NCT01442064). The first cohort of this study enrolled two subsets of patients: ranibizumab experienced and ranibizumab-naive. Patients were enrolled within 14 days of completion of the 24 month treatment phase of the previous study.

Official Title
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An Open-Label, Multicenter Extension Study to Evaluate the Safety and Tolerability of Ranibizumab in Subjects With Choroidal Neovascularization (CNV) Secondary to Age-Related Macular Degeneration (AMD) or Macular Edema Secondary to Retinal Vein Occlusion (RVO) Who Have Completed a Genentech-Sponsored Ranibizumab Study

Conditions
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Choroidal Neovascularization, Age-related Macular Degeneration

Intervention / Treatment
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* Drug: Ranibizumab 0.5 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent form. Completion of the treatment phase (through Month 24) of a Genentech-sponsored ranibizumab study for AMD (FVF2598g, FVF2587g, or FVF2428g) (Cohort 1) Expectation by the investigator that the subject may potentially benefit from intravitreal anti-vascular endothelial growth factor (VEGF) treatment Exclusion Criteria: Previous subfoveal focal laser photocoagulation in the study eye Previous pegaptanib sodium injection in the study eye Laser photocoagulation (juxtafoveal or extrafoveal) in the study eye within 1 month preceding Day 0 of this extension study History of submacular surgery or other surgical intervention for AMD in the study eye History of glaucoma filtering surgery in the study eye History of corneal transplant in the study eye Concurrent use of systemic anti-EGF agents Use of AMD treatments not approved by the FDA Use of intravitreal Avastin(R) (bevacizumab) in the study eye and/or fellow eye CNV in either eye due to other causes than AMD, such as ocular histoplasmosis, trauma, or pathologic myopia for Cohort 1 History of rhegmatogenous retinal detachment or macular hole (Stage 3 or 4) in the study eye History of idiopathic or autoimmune-associated uveitis in either eye Uncontrolled glaucoma in the study eye (defined as intraocular pressure ≥ 30 mmHg despite treatment with antiglaucoma medication) Pregnancy or lactation Premenopausal women not using adequate contraception History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use an investigational drug or that might affect interpretation of the results of the study or render the subject at high risk for treatment complications Current treatment for active systemic infection Inability to comply with study or follow-up procedures

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: Ranibizumad 0.5 mg<br>Ranibizumab 0.5 mg intravitreal injection 0.5 mg in the study eye on an as needed basis no more frequently than every 30 days (no more than 12 injections per year) for 24 months. Dosing interval was determined by the investigator, on the basis of clinical evaluations and judgment. | Drug: Ranibizumab 0.5 mg<br>* Ranibizumab intravitreal injection 0.5 mg in a single-dose regimen given on an as needed basis no more frequently than every 30 days (no more than 12 injections per year)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Ocular Adverse Events | Number of participants with ocular adverse events in the following categories: any adverse events, serious adverse events, adverse events leading to study discontinuation, endophthalmitis and intraocular inflammation that occurred in the study eye (the eye that received all study drug injections) and the fellow eye (other eye). Only adverse events that occurred during this extension study are reported. For subjects in the crossover groups who started their first ranibizumab injection in this extension study, adverse events that occurred prior to any ranibizumab injection were also excluded. | 36 months | 
| Number of Participants With Non-ocular Adverse Events | Number of participants with non-ocular adverse events (not occurring in the eye) in the following categories: any adverse events, serious adverse events, adverse events leading to study discontinuation and death. Only adverse events that occurred during this extension study are reported. For subjects in the crossover groups who started their first ranibizumab injection in this extension study, adverse events that occurred prior to any ranibizumab injection were also excluded. Additional information about adverse events can be found in the adverse events section. | 36 months | 
| Number of Participants With Positive Serum Antibodies to Ranibizumab at Month 12 and Month 24 | Serum samples for the evaluation of antibodies to Ranibizumab were collected at Month 12 and Month 24 and were sent to a reference laboratory for analysis. If an injection of Ranibizumab was required at the visit, the samples were collected prior to the injection. | Month 12 and 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Best Corrected Visual Acuity (BCVA) at a Starting Test Distance of 2 Meters | Change from baseline in Best corrected visual acuity (BCVA) was assessed by the number of letters a patient could read correctly on the Early Treatment Diabetic Retinopathy Study (ETDRS) Eye Chart at a starting test distance of 2 meters. An increase in the number of letters read indicates improvement in visual acuity. | Extension study baseline, Months 3, 6, 9, 12, 15, 18, 21 and 24 | 
| Change From Baseline in Best Corrected Visual Acuity at a Starting Test Distance of 4 Meters | Change from baseline in Best corrected visual acuity (BCVA) was assessed by the number of letters a patient could read correctly on the Early Treatment Diabetic Retinopathy Study (ETDRS) Eye Chart at a starting test distance of 4 meters. An increase in the number of letters read indicates improvement in visual acuity. | Extension study baseline, Months 12 and 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CNV, Lucentis, AMD, Age-related macular degeneration, RVO