Verteporfin Photodynamic Therapy Administered in Conjunction With Ranibizumab in Patients With Subfoveal Choroidal Neovascularization Secondary to Age-related Macular Degeneration (AMD)

Study Overview
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Brief Summary
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This study will evaluate the effect of combination therapy with verteporfin photodynamic therapy and ranibizumab on visual acuity compared to ranibizumab monotherapy and the durability of response observed in patients with choroidal neovascularization secondary to age-related macular degeneration

Official Title
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24-month Randomized, Double-masked, Controlled, Multicenter, Phase II Study Assessing Safety and Efficacy of Verteporfin Photodynamic Therapy Administered in Conjunction With Ranibizumab Versus Ranibizumab Monotherapy in Patients With Subfoveal Choroidal Neovascularization Secondary to AMD.

Conditions
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Macular Degeneration, Choroidal Neovascularization

Intervention / Treatment
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* Drug: Verteporfin Photodynamic Therapy
* Drug: Ranibizumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects of either gender age 50 years or older Subfoveal choriodal neovascularization (CNV) due to age-related macular degeneration (AMD) Exclusion Criteria: Choriodal neovascularization due to causes other than AMD Prior treatment for neovascular AMD in the study eye Other protocol-defined inclusion/exclusion criteria may apply

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Verteporfin + Ranibizumab<br>Verteporfin (6 mg/m^2) photodynamic therapy (PDT) and ranibizumab (0.5 mg). Patients received three consecutive monthly ranibizumab injections starting on Day 1, and then as needed at intervals of at least 30 days based on retreatment criteria. These patients also received verteporfin PDT on Day 1 and then as needed from Month 3 at intervals of at least 90 days based on the retreatment criteria. From month 3 onward, retreatments were determined based on study-specific retreatment criteria that included retinal thickness by Optical Coherence Tomography (OCT), sub-retinal hemorrhage evaluated by ophthalmoscopic examination, visual acuity assessed using Early treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart and CNV leakage assessed by fluorescein angiography (FA). | Drug: Verteporfin Photodynamic Therapy<br>* After a 10-minute intravenous infusion of verteporfin at a dose of 6 mg/m^2 body surface area, verteporfin was activated by light application of 50 J/cm^2 to the study eye, begun 15 minutes after the start of the infusion.<br>* Other names: Visudyne;Drug: Ranibizumab<br>* Ranibizumab 0.5 mg (0.05 mL of 10 mg/mL solution for injection) administered as an intravitreal injection<br>* Other names: Lucentis;|
| Active Comparator: Ranibizumab Monotherapy<br>Patients received three consecutive monthly ranibizumab injections starting on Day 1 and then as needed from Month 3 based on the retreatment criteria. These patients were also administered verteporfin placebo infusion with sham PDT on Day 1 and then as needed from Month 3 at intervals of at least 90 days based on the retreatment criteria. From month 3 onward, retreatments were determined based on study-specific retreatment criteria that included retinal thickness by Optical Coherence Tomography (OCT), sub-retinal hemorrhage evaluated by ophthalmoscopic examination, visual acuity assessed using Early treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart and CNV leakage assessed by fluorescein angiography (FA). | Drug: Ranibizumab<br>* Ranibizumab 0.5 mg (0.05 mL of 10 mg/mL solution for injection) administered as an intravitreal injection<br>* Other names: Lucentis;Drug: Placebo<br>* As a placebo for verteporfin photodynamic therapy (for masking purposes), patients were administered a 10-minute intravenous infusion of 5% dextrose solution, followed by light application of 50 J/cm^2 to the study eye, begun 15 minutes after the start of infusion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Best-corrected Visual Acuity (BCVA) at Month 12. | BCVA score was based on the number of letters read correctly on the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart assessed at a starting distance of 4 meters. An ETDRS visual acuity score of 85 is approximately 20/20. An increase in the VA score indicates improvement in visual acuity. | Baseline and Month 12 | 
| Percent of Participants With a Treatment-free Interval of at Least 3 Months Following the Month 2 Visit | The number of patients with a ranibizumab treatment-free interval, ie, no active ranibizumab treatments for at least 3 months duration (at least 2 consecutive monthly visits), anytime following the Month 2 ranibizumab treatment. Only active ranibizumab treatments were considered. | Month 2 to Month 11 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients With Fluorescein Leakage in the Study Eye at Month 12 | The proportion of patients with leakage of the study eye was assessed at the Central Reading Center (CRC) using Fluorescein angiography (FA). | Month 12 | 
| Mean Change in Total Area of Leakage (Observed) of the Study Eye at Month 12 | Fluorescein angiography (FA) was used to assess the mean change of leakage of the study eye at the Central Reading Center (CRC). A negative change from baseline indicates improvement, ie, less leakage. | Baseline and Month 12 | 
| Mean Change in Central Retinal Thickness of the Study Eye at Month 12 | Optical coherence tomography (OCT) was used to assess the mean change in retinal thickness of the study eye at the Central Reading Center (CRC). A negative change from baseline indicates improvement, ie, less thickness. | Baseline and Month 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Age-related macular degeneration, AMD, Choroidal neovascularization, Verteporfin, Ranibizumab