Safety Study of 2.0mg Lucentis to Treat Polypoidal Choroidal Vasculopathy

Study Overview
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Brief Summary
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This Phase I/II study will investigate the safety and tolerability of intravitreally administered 0.5mg and 1.0 or 2.0mg Ranibizumab in three monthly doses followed by a 9 month period of criteria-based, as-needed retreatment and 12 month of drug safety follow up in subjects with exudative polypoidal choroidal vasculopathy (PCV) for a total of 24 months.

Detailed Description
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Twenty eyes will be randomized will receive 3 consecutive monthly intravitreal 1.0 or 2.0 mg/0.5mg (3:1 ratio) Ranibizumab injection with the first injection occuring at Day 0 and second and third injection occuring at month 1 and month 2 respectively. Retreatment with intravitreal Ranibizumab or other therapies will be at the investigators discretion but guidelines for recommended retreatment.

Official Title
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Treatment of Polypoidal Choroidal Vasculopathy With High Dose Ranibizumab (Lucentis): A Phase I Safety Study.

Conditions
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Polypoidal Choroidal Vasculopathy

Intervention / Treatment
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* Drug: ranibizumab 0.5 or 2.0 mg/0.05 cc


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and Females >18 years of age. Females of child bearing potential will undergo urine pregnancy testing and be required to use appropriate methods of birth control. ICG and fluorescein angiographic characteristics consistent with active, leaking PCV with subfoveal lesions and/or subfoveal hemorrhage, lipid exudates, PED or fluid diagnosed within the past 6 months or diagnosed as newly active within the past 6 months. Subjects who completed the 24 month follow up in the original FVF3671s protocol may enter the study without necessarily demonstrating active exudative PCV at enrollment. Best-Corrected ETDRS Visual Acuity at 4 meters between 20/20 - 20/800. Lesion size - no limitations. Lesions Characteristics - leaking lesions consistent with PCV. No limitations on hemorrhage, fibrosis or atrophy. No therapy (includes non foveal laser, PDT, intravitreal steroids, TTT, radiotherapy, or anti-VEGF therapy) or intraocular surgery within the past 30 days for any condition. Clear ocular media to allow for photography/angiography. Ability to provide written informed consent and comply with study assessments for the full duration of the study. Exclusion Criteria: Patients with features of age related macular degeneration such as abundant drusen and demographic features consistent with this diagnosis. Allergy to Fluorescein, ICG, Iodine, Shellfish. Pregnancy (positive pregnancy test) Any other condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated. Participation in another simultaneous medical investigation or trial. Exclude other anti-VEGF agents as therapy options. History of previous subfoveal laser. Advanced glaucoma (IOP > 25 or cup/disc ration > 0.8) Any condition in the opinion of the investigator that would interfere with disease status/progression or jeopardize patients' participation in the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ranibizumab 1.0 or 2.0 mg (HIGH DOSE)<br>Intraocular injection of 1.0 or 2.0 mg/0.05 cc ranibizumab. Photodynamic therapy with visudyne or laser photocoagulation or intravitreal steroids may be considered as monotherapy or in combination with Ranibizumab at the investigator's discretion if rescue criteria are met | Drug: ranibizumab 0.5 or 2.0 mg/0.05 cc<br>* ranibizumab (3:1 ratio of 2mg:0.5 mg ranibizumab) administered in three initial monthly doses followed by a 9 month period of criteria-based, as-needed retreatment and 12 month off drug safety follow up.<br>* Other names: Lucentis;|
| Active Comparator: Ranibizumab 0.5 mg<br>Intraocular injection of 0.5 mg/0.05 cc ranibizumab. Photodynamic therapy with visudyne or laser photocoagulation or intravitreal steroids may be considered as monotherapy or in combination with Ranibizumab at the investigator's discretion if rescue criteria are met | Drug: ranibizumab 0.5 or 2.0 mg/0.05 cc<br>* ranibizumab (3:1 ratio of 2mg:0.5 mg ranibizumab) administered in three initial monthly doses followed by a 9 month period of criteria-based, as-needed retreatment and 12 month off drug safety follow up.<br>* Other names: Lucentis;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and Severity of Ocular and Systemic Adverse Events Will be Compared Between the 2.0mg or 1.0mg (HIGH DOSE) and 0.5 mg Groups. | Examples include 30 letter loss, major subretinal hemorrhage, involving 75% or more clinical macula (arcade to arcade), disease related vitreous hemorrhage, injection-related endophthalmitis, retinal detachment, vitreous hemorrhage, study drug/procedure - related uveitis, incidence and severity of other adverse events, as identified by physical examination, subject reporting, and changes in vital signs. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Best Corrected Visual Acuity Letter Change at 4 Meters Between Baseline and 12 Months |  | 12 months | 
| Change in Mean Central Foveal Thickness From Baseline |  | 12 Months | 
| Mean Change From Baseline in Total Area of FA CNV Leakage Over 12 Months |  | 12 Months | 
| Number of Participants at Month 3 With Best Corrected Visual Acuity Gain of 5, 10, and 15 or More Letters |  | 3 Months | 
| Number of Participants at Month 6 With Best Corrected Visual Acuity Gain of 5, 10, and 15 or More Letters |  | 6 months | 
| Number of Participants at Month 9 With Best Corrected Visual Acuity Gain of 5, 10, and 15 or More Letters |  | 9 Months | 
| Number of Participants at Month 12 With Best Corrected Visual Acuity Gain of 5, 10, and 15 or More Letters |  | 12 Months | 
| Mean Change Best Corrected Visual Acuity at 4 Meters at Baseline, Month 3, Month 6, Month 9, and Month 12 |  | 12 months | 
| Number of Participants at Month 3 With Best Corrected Visual Acuity Loss at 4 Meters of 5, 10 and 15 or More Letters |  | 3 months | 
| Number of Participants at Month 6 With Best Corrected Visual Acuity Loss at 4 Meters of 5, 10 and 15 or More Letters |  | 6 months | 
| Number of Participants at Month 9 With Best Corrected Visual Acuity Loss at 4 Meters of 5, 10 and 15 or More Letters |  | 9 months | 
| Number of Participants at Month 12 With Best Corrected Visual Acuity Loss at 4 Meters of 5, 10 and 15 or More Letters |  | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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polypoidal choroidal vasculopathy, choroidal neovascularization, ranibizumab, Lucentis