Intravitreal Bevacizumab vs.Combination Therapy for CNV Due to Other Than AMD

Study Overview
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Brief Summary
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Anti-VEGF therapy has been proven efficacious for the wet (neovascular) form of macular degeneration and may be beneficial for the treatment of choroidal neovascularization (CNV) due to other causes. The limitation of this type of treatment is the necessity for frequent intraocular injections. The purpose of this study is to determine if using anti-VEGF therapy in combination with photodynamic therapy can reduce the number of treatments needed with monotherapy while achieving similar visual results. There are ongoing multicenter trials evaluating combination therapy in patients with wet AMD but no similar trial for patients with CNV due to non-AMD causes. Therefore, in this study the investigators will focus on patients with CNV not due to AMD.

Official Title
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Pilot Study of Intravitreal Bevacizumab vs. Combination Therapy for Choroidal Neovascularization Secondary to Causes Other Than Age-related Macular Degeneration

Conditions
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Choroidal Neovascularization, Myopia, Punctate Inner Choroidopathy (PIC), Multifocal Choroiditis, Ocular Histoplasmosis Syndrome, Central Serous Chorioretinopathy (CSC), Angioid Streaks, Trauma, or Hereditary Eye Diseases

Intervention / Treatment
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* Drug: Bevacizumab (Avastin; Genentech, Inc.)
* Drug: Bevacizumab, Dexamethasone, Verteporfin Photodynamic Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ability to provide written informed consent and comply with study assessments for the full duration of the study. Age > 18 years Clinical diagnosis of choroidal neovascularization secondary to the following causes: ocular histoplasmosis, toxoplasmosis, idiopathic, angioid streaks, choroidal ruptures, intraocular inflammation (without signs of active uveitis i.e. multifocal choroiditis), central serous retinopathy and pathologic Myopia. Only one eye will be assessed in the study. If both eyes are eligible, the investigator and patient will determine which eye is to be treated, considering such factors as disease duration, and likelihood of response to treatment. Clear media and dilation to permit good stereo fundus photography Evidence of active CNV present on OCT images manifest by subretinal fluid, intraretinal fluid or retinal thickening ≥ 250 µm Best corrected VA in the study eye must be 20/40 and to 20/400 at 4 meters using ETDRS protocol. Exclusion Criteria: Pregnancy or lactation Premenopausal women not using adequate contraception The following are considered effective means of contraception: surgical sterilization; use of oral contraceptives; barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel; and IUD; or contraceptive hormone implant or patch. CNV secondary to AMD Diabetic Retinopathy Prior enrollment in clinical studies in the study eye Any other condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated Previous participation in another simultaneous medical investigation or trial within 1 month preceding Day 0 (excluding vitamins and minerals) Use of drug or treatment related or unrelated to their condition within 30 days prior to enrollment (Verteporfin, pegaptanib, ranibizumab, bevacizumab, triamcinilone or other AMD therapy in study eye) Concurrent use of systemic anti-VEGF therapy Any other ocular condition the investigator believes would pose a significant hazard to the subject if investigational treatment were initiated History of allergy to fluorescein Inability to obtain fundus photographs or FAs of sufficient quality to document CNV Inability to comply with study or follow-up procedures 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 of 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 History of uncontrolled glaucoma (defined as intraocular pressure >30mmHg despite treatment with anti-glaucoma medication) or filtering surgery in the study eye Family history of glaucoma Patients who have undergone intraocular surgery within last 2 months Aphakia or absence of the posterior capsule in the study eye Previous violation of the posterior capsule in the study eye is also excluded unless it occurred as a result of YAG posterior capsulotomy in association with prior, posterior chamber intraocular lens implantation.

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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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Monotherapy<br>Bevacizumab (Avastin; Genentech, Inc.)1.25 mg by intravitreal injection on day 0 and then prn (as-needed) based on ophthalmic examination and OCT findings | Drug: Bevacizumab (Avastin; Genentech, Inc.)<br>* 1.25 mg bevacizumab (Avastin; Genentech, Inc.) by intravitreal injection<br>|
| Active Comparator: Combination therapy<br>Intravitreal injection of bevacizumab 1.25 mg (Avastin; Genentech, Inc.) combined with reduced fluence PDT(Visudyne®; Novartis,) and 200 ug of intravitreal dexamethasone(4mg/ml, American regent, Inc) on Day 0 and then monthly retreatment with bevacizumab as-needed and triple therapy every 3 months as-needed. | Drug: Bevacizumab, Dexamethasone, Verteporfin Photodynamic Therapy<br>* Intravitreal injection of 1.25 mg bevacizumab (Avastin; Genentech, Inc.) combined with reduced-fluence verteporfin PDT (Visudyne®; Novartis) and 200ug of intravitreal dexamethasone<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean number of treatments per group |  | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change in visual acuity from baseline | Mean change in visual acuity from baseline Proportion of subjects losing ≤8 letters (≈1.5 lines) from baseline Proportion gaining ≥15 letters from baseline Proportion with a Snellen equivalent of 20/200 or worse (legal blindness = 20/200 or worse in both eyes) Mean change from baseline in total area of CNV and total area of leakage from CNV from baseline to month 12 by FA Mean change in central subfield macular thickness (CMT) measured by OCT from baseline to month 12 Change of in areas of hypoautofluorescence (indicating atrophy) from baseline to month 12 | 12 months |