Efficacy/Safety of Verteporfin Photodynamic Therapy and Ranibizumab Compared With Ranibizumab in Patients With Subfoveal Choroidal Neovascularization

Study Overview
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Brief Summary
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This study evaluated the effect of combination therapy with verteporfin photodynamic therapy and ranibizumab on visual acuity and anatomic outcomes 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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A 24-month Randomized, Double-masked, Controlled, Multicenter, Phase IIIB 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 Age-related Macular Degeneration

Conditions
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Macular Degeneration, Choroidal Neovascularization

Intervention / Treatment
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* Drug: Verteporfin Photodynamic Therapy
* Drug: Ranibizumab
* Drug: Verteporfin Placebo
* Drug: Ranibizumab 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 choroidal neovascularization (CNV) due to age-related macular degeneration (AMD) Exclusion Criteria: Choroidal 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 With Standard Fluence Rate Plus Ranibizumab<br>Patients received three consecutive monthly ranibizumab injections on Day 1 and at Months 1 and 2, and thereafter as needed at intervals of at least 30 days based on retreatment criteria. These patients also received verteporfin photodynamic therapy (PDT) with standard fluence (SF) rate 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 choroidal neovascularization (CNV) leakage assessed by fluorescein angiography (FA). Patients received sham intravitreal injections for the first 12 months if retreatment with ranibizumab was not warranted based on the retreatment criteria. | 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 (Standard Fluence rate) or 25 J/cm^2 (Reduced Fluence rate) to the study eye, begun 15 minutes after the start of the infusion.<br>* Other names: Visudyne;Drug: Ranibizumab<br>* Ranibizumab 0.5 mg administered as an intravitreal injection.<br>* Other names: Lucentis;Drug: Ranibizumab Placebo<br>* To maintain masking, patients in the combination groups received sham intravitreal injections whenever retreatment with active Ranibizumab was not warranted based on the retreatment algorithm.<br>|
| Active Comparator: Ranibizumab Monotherapy<br>Patients received monthly ranibizumab injections for 12 months and thereafter as needed 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. 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 choroidal neovascularization (CNV) leakage assessed by fluorescein angiography (FA). | Drug: Ranibizumab<br>* Ranibizumab 0.5 mg administered as an intravitreal injection.<br>* Other names: Lucentis;Drug: Verteporfin Placebo<br>* To maintain masking, as a placebo for verteporfin photodynamic therapy, 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>|
| Experimental: Verteporfin With Reduced Fluence Rate Plus Ranibizumab<br>Patients received three consecutive monthly ranibizumab injections on Day 1 and at Months 1 and 2, and thereafter as needed at intervals of at least 30 days based on retreatment criteria. These patients also received verteporfin PDT with reduced fluence (RF) rate 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 choroidal neovascularization (CNV) leakage assessed by fluorescein angiography (FA). Patients received sham intravitreal injections for the first 12 months if retreatment with ranibizumab was not warranted based on the retreatment criteria. | 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 (Standard Fluence rate) or 25 J/cm^2 (Reduced Fluence rate) to the study eye, begun 15 minutes after the start of the infusion.<br>* Other names: Visudyne;Drug: Ranibizumab<br>* Ranibizumab 0.5 mg administered as an intravitreal injection.<br>* Other names: Lucentis;Drug: Ranibizumab Placebo<br>* To maintain masking, patients in the combination groups received sham intravitreal injections whenever retreatment with active Ranibizumab was not warranted based on the retreatment algorithm.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) of the Study Eye 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 Patients 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 up to Month 11 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Total Area of Leakage of the Study Eye at Month 12 | Total area of leakage of the study eye was assessed at the Central Reading Center (CRC) using Fluorescein angiography (FA). | Baseline and Month 12 | 
| Percentage of Patients With Fluorescein Leakage in the Study Eye at Month 12 | The percentage of patients with leakage of the study eye was assessed at the Central Reading Center (CRC) using Fluorescein angiography (FA). | Month 12 | 
| Change From Baseline in Central Retinal Thickness at Month 12 | Optical coherence tomography was performed in the study eyes and the evaluations of the images were performed by the central reading center. | 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