Reduced Fluence Visudyne-Anti-VEGF-Dexamethasone In Combination for AMD Lesions (RADICAL)

Study Overview
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Brief Summary
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The objective of this study is to determine if combination therapy (reduced-fluence Visudyne followed by Lucentis [within 2 hours] or either of two regimens of reduced-fluence Visudyne followed by Lucentis-Dexamethasone triple therapy [within 2 hours]) reduces retreatment rates compared with Lucentis monotherapy while maintaining similar vision outcomes and an acceptable safety profile.

Official Title
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A Multicenter, Randomized, Single-masked Study Comparing Reduced-fluence Visudyne®-Lucentis® Combination Therapies and Lucentis® Monotherapy in Subjects With Choroidal Neovascularization (CNV) Secondary to AMD.

Conditions
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Choroidal Neovascularization, Macular Degeneration

Intervention / Treatment
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* Drug: verteporfin
* Drug: verteporfin
* Drug: ranibizumab
* Drug: dexamethasone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Treatment naive for choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) in the study eye except for laser treatment outside the subfoveal area Subfoveal CNV due to AMD CNV must be = or >50 % of the entire lesion All lesion composition types with a lesion greatest linear dimension (GLD) < 5400 microns (approximately = or <9 disc areas [DA]) Best-corrected Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA score) of 25 - 73 letters (approximate Snellen equivalent of 20/40 - 20/320), inclusive Exclusion Criteria: Subfoveal geographic atrophy or subfoveal fibrosis of the study eye Intraocular surgery within 3 months of enrollment Inability to attend the protocol-required visits Known allergies or hypersensitivity to any of the study treatments. Other systemic diseases or active uncontrolled infections that would make subject a poor medical risk Uncontrolled glaucoma, defined as (1)subject is on >1 glaucoma medication (includes combination treatments) or (2)subject has glaucoma that could lead to progressive visual field deterioration If subject has had a stroke within the last year

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1/4 Fluence Triple Therapy<br>Very low fluence Visudyne followed by intravitreal Lucentis-Dexamethasone triple therapy [within 2 hours] administered on Day 0, and then as required every 2 months thereafter | Drug: verteporfin<br>* Very-low fluence Visudyne (15 J/cm2, 180 mW/cm2, 83 seconds)<br>* Other names: photodynamic therapy;Drug: ranibizumab<br>* 0.5 mg intravitreal injection<br>* Other names: Lucentis;Drug: dexamethasone<br>* 0.5 mg intravitreal injection<br>|
| Experimental: 1/2 Fluence Triple Therapy<br>Reduced-fluence Visudyne followed by intravitreal Lucentis-Dexamethasone triple therapy [within 2 hours] administered on Day 0, and then as required every 2 months thereafter | Drug: verteporfin<br>* Reduced-fluence Visudyne (25 J/cm2, 300 mW/cm2, 83 seconds)<br>* Other names: photodynamic therapy;Drug: ranibizumab<br>* 0.5 mg intravitreal injection<br>* Other names: Lucentis;Drug: dexamethasone<br>* 0.5 mg intravitreal injection<br>|
| Experimental: 1/2 Fluence Double Therapy<br>Reduced-fluence Visudyne followed by Lucentis double therapy [within 2 hours] administered on Day 0, and then as required every 2 months thereafter | Drug: verteporfin<br>* Reduced-fluence Visudyne (25 J/cm2, 300 mW/cm2, 83 seconds)<br>* Other names: photodynamic therapy;Drug: ranibizumab<br>* 0.5 mg intravitreal injection<br>* Other names: Lucentis;|
| Experimental: Ranibizumab<br>Lucentis monotherapy administered on Day 0, Month 1 and Month 2, and then as required monthly thereafter | Drug: ranibizumab<br>* 0.5 mg intravitreal injection<br>* Other names: Lucentis;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Number of Retreatments (Day 0 Excluded) | Retreatment was defined in the protocol as study treatment administered after Day 0. For the analyses of retreatment, any study treatment that was administered was considered to be a retreatment, and combination therapy was considered to be one retreatment, even though two or three treatment procedures were done. In the combination therapy groups, if a ranibizumab injection was given because retreatment was indicated and the previous combination treatment was less than 2 months before, the ranibizumab injection was counted as a retreatment. | Month 1 to Month 12 | 
| Mean Change From Baseline in Study Eye Best-corrected VA Score (ETDRS Chart) | Early Treatment Diabetic Retinopathy Study (ETDRS) method at 4 meters. Worst = 0; best = 100 | Baseline to Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Number of Retreatments (Day 0 Excluded) | Retreatment was defined in the protocol as study treatment administered after Day 0. For the analyses of retreatment, any study treatment that was administered was considered to be a retreatment, and combination therapy was considered to be one retreatment, even though two or three treatment procedures were done. In the combination therapy groups, if a ranibizumab injection was given because retreatment was indicated and the previous combination treatment was less than 2 months before, the ranibizumab injection was counted as a retreatment. | Month 1 to Month 24 | 
| Mean Change From Baseline in Study Eye Best-Corrected VA Score | Early Treatment Diabetic Retinopathy Study (ETDRS) method at 4 meters. Worst = 0; best = 100 | Baseline to Month 24 | 
| Percentage of Subjects With >=15 Letters of Visual Acuity Gained From Baseline |  | Baseline to Month 12, Baseline to Month 24 | 
| Percentage of Subjects With >=0 Letter Gain of Visual Acuity From Baseline |  | Baseline to Month 12, Baseline to Month 24 | 
| Percentage of Subjects With >=15 Letters of Visual Acuity Lost From Baseline |  | Baseline to Month 12, Baseline to Month 24 | 
| Mean Change From Baseline in Central Retinal Thickness |  | Baseline to Month 12, Baseline to Month 24 | 
| Mean Change From Baseline in Lesion Size | Mean change from baseline in lesion size measured as greatest linear dimension (GLD) of the lesion | Baseline to Month 12, Baseline to Month 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Macular Degeneration, AMD, CNV, Choroidal neovascularization, Photodynamic therapy, CNV Secondary to Age Related Macular Degeneration