A Safety and Efficacy Study Comparing the Combination Treatments of Verteporfin Therapy Plus One of Two Different Doses of Intravitreal Triamcinolone Acetonide and the Verteporfin Therapy Plus Intravitreal Pegaptanib

Study Overview
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Brief Summary
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To evaluate the safety and efficacy of the combination treatments in wet age-related macular degeneration. The combination treatment consists of verteporfin photodynamic therapy and either triamcinolone acetonide or pegaptanib added as an intravitreal injection.

Official Title
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A 24-month Randomized, Double-masked, Sham Controlled, Multicenter, Phase IIIB Study Comparing Photodynamic Therapy With Verteporfin (Visudyne®) Plus Two Different Dose Regimens of Intravitreal Triamcinolone Acetonide (1 mg and 4 mg) Versus Visudyne® Plus Intravitreal Pegaptanib(Macugen®) 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: Pegaptanib
* Drug: Triamcinolone acetonide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age >50 all types of untreated subfoveal choroidal neovascularization secondary to AMD lesion size <5400 microns in greater linear dimension (GLD) Exclusion Criteria: have a history of prior photodynamic therapy, external beam radiation, subfoveal focal laser photocoagulation, submacular surgery, or transpupillary thermotherapy known allergy to verteporfin, triamcinolone or pegaptanib have received prior treatment with Macugen, or other anti-angiogenic compound or any investigational treatment (e.g. Ruboxistaurin, Lucentis [ranibizumab], Retaane [anecortave acetate], squalamine, siRNA, VEGF-Trap etc.) for neovascular AMD have the presence of fibrosis, hemorrhage, pigment epithelial detachments, tear (tip) of the retinal pigment epithelium or other hypoflourescent lesions obscuring greater than 50% of the CNV lesion have had previous pars plana vitrectomy in the study eye Other protocol-specified inclusion/exclusion criteria applied.

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 and Triamcinolone 1 mg<br>Participants received Verteporfin photodynamic therapy and 1 mg triamcinolone acetonide intravitreal injection at the baseline visit. After the baseline visit, these participants received Verteporfin and triamcinolone acetonide 1 mg at every 3 month visit up to Month 9 only if leakage was detected on the fluorescein angiogram. At the 1.5, 4.5, 7.5 and 10.5 month follow-up visits participants received a sham injection. Starting from Month 12, if patients experienced ≥ 10 letters vision loss from the previous visit, they were treated at the investigators' discretion with available standard of care therapy. | 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 infusion.<br>* Other names: Visudyne;Drug: Triamcinolone acetonide<br>* Triamcinolone acetonide administered by intravitreal injection.<br>* Other names: Kenalog-40®;|
| Experimental: Verteporfin and Triamcinolone 4 mg<br>Participants received Verteporfin photodynamic therapy and 4 mg triamcinolone acetonide intravitreal injection at the baseline visit. After the baseline visit, these participants received Verteporfin and triamcinolone acetonide 4 mg at every 3 month visit up to Month 9 only if leakage was detected on the fluorescein angiogram. At the 1.5, 4.5, 7.5 and 10.5 month follow-up visits participants received a sham injection. Starting from Month 12, if patients experienced ≥ 10 letters vision loss from the previous visit, they were treated at the investigators' discretion with available standard of care therapy. | 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 infusion.<br>* Other names: Visudyne;Drug: Triamcinolone acetonide<br>* Triamcinolone acetonide administered by intravitreal injection.<br>* Other names: Kenalog-40®;|
| Active Comparator: Verteporfin and Pegaptanib<br>Participants received Verteporfin photodynamic therapy and 0.3 mg Pegaptanib at the baseline visit. After the baseline visit, these participants received pegaptanib every 1.5 months up until and including the 10.5 month visit. After the baseline visit, these participants also received verteporfin at every 3 month visit up to Month 9 only if leakage was detected on the fluorescein angiogram. Starting from Month 12, if participants experienced ≥ 10 letters vision loss from the previous visit, they were treated at the investigator's discretion with available standard of care therapy. | 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 infusion.<br>* Other names: Visudyne;Drug: Pegaptanib<br>* Pegaptanib sodium 0.3 mg administered by intravitreal injection.<br>* Other names: Macugen;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Lose Less Than 15 Letters of Best Corrected Visual Acuity (BCVA) at 12 Months From Baseline. | 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. A decrease in score indicates worsening of vision. This outcome assessed the percentage of participants who lost less than 15 letters of visual acuity at 12 months as compared with baseline. | Baseline to Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Gain of 5 or More Letters of Best Corrected Visual Acuity From Baseline to 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 increased score indicates improvement in acuity. This outcome assessed the percentage of participants who gained 5 or more letters of visual acuity at 12 months compared with baseline. | Baseline to Month 12 | 
| Percentage of Participants With Gain of BCVA of 10 or More Letters at 12 Months | 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 increased score indicates improvement in acuity. This outcome assessed the percentage of participants who gained 10 or more letters of visual acuity at 12 months as compared with baseline. | Baseline to Month 12 | 
| Percentage of Participants With Gain of BCVA Score of 15 or More Letters 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 increased score indicates improvement in acuity. This outcome assessed the percentage of participants who gained 15 or more letters of visual acuity at 12 months as compared with baseline. | Baseline to Month 12 | 
| Number of Participants Requiring Verteporfin Treatment Throughout the Study | Participants received study drug at the Baseline visit and subsequent retreatment at 3 month intervals if leakage was detected on the fluorescein angiogram. The cumulative distribution of the number of treatments is shown per arm. | Baseline to Month 12 | 
| Mean Change From Baseline in Total Area of Lesion at 12 Months | Fluorescein angiography (FA) was used to assess total lesion area. All angiographs were sent to the Central Reading Center (CRC) for analysis. | Baseline to Month 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AMD, age-related macular degeneration, choroidal neovascularization