Efficacy and Safety of Ranibizumab in Patients With Visual Impairment Due to Choroidal Neovascularization Secondary to Pathologic Myopia

Study Overview
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Brief Summary
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This study is designed to evaluate the efficacy and safety of two different dosing regimens of 0.5 mg ranibizumab given as intravitreal injection in comparison to verteporfin PDT in patients with visual impairment due to choroidal neovascularization (CNV) secondary to pathologic myopia (PM).

Official Title
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A 12 Month, Phase III, Randomized, Double-masked, Multicenter, Active-controlled Study to Evaluate the Efficacy and Safety of Two Different Dosing Regimens of 0.5 mg Ranibizumab vs. Verteporfin PDT in Patients With Visual Impairment Due to Choroidal Neovascularization Secondary to Pathologic Myopia

Conditions
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Pathological Myopia

Intervention / Treatment
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* Drug: Ranibizumab
* Drug: Verteporfin PDT
* Drug: Sham Ranibizumab
* Drug: Sham verteporfin PDT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Visual impairment due to choroidal neovascularization (CNV) secondary to PM Best corrected visual acuity (BCVA) in the study eye > 24 and < 78 Early Treatment Diabetic Retinopathy Study (ETDRS) letters High myopia (> -6D), anterior-posterior elongation > 26 mm; posterior changes compatible with the pathologic myopia Either lesion types in the study eye: subfoveal, juxtafoveal, extrafoveal Exclusion Criteria: Patients with uncontrolled systemic or ocular diseases Blood pressure > 150/90 mmHg History of pan-retinal, focal/grid laser photocoagulation or intraocular treatment with any anti-VEGF or vPDT in the study eye Intravitreal treatment with corticosteroids or intraocular surgery within last 3 months in the study eye Other protocol-defined inclusion/exclusion criteria may apply

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ranibizumab driven by disease activity<br>Participants received active ranibizumab on day 1. Thereafter they received ranibizumab treatment based on disease activity criteria | Drug: Ranibizumab<br>* 0.5 mg ranibizumab intravitreal injection<br>Drug: Sham Ranibizumab<br>* Empty vial to mimic the intravitreal injection<br>Drug: Sham verteporfin PDT<br>* Sham vPDT intravenous infusion of dextrose 5% solution followed by light application (PDT).<br>|
| Experimental: Ranibizumab driven by stabilization criteria<br>Participants received ranibizumab on day 1 and month 1. Thereafter they received ranibizumab based on stabilization criteria for visual acuity | Drug: Ranibizumab<br>* 0.5 mg ranibizumab intravitreal injection<br>Drug: Sham Ranibizumab<br>* Empty vial to mimic the intravitreal injection<br>Drug: Sham verteporfin PDT<br>* Sham vPDT intravenous infusion of dextrose 5% solution followed by light application (PDT).<br>|
| Active Comparator: Verteporfin PDT<br>Participants received active vPDT on day 1. From month 3 onwards participants could receive ranibizumab, vPDT or a combination of the two if needed. | Drug: Ranibizumab<br>* 0.5 mg ranibizumab intravitreal injection<br>Drug: Verteporfin PDT<br>* Verteporfin (6 mg/m2) intravenous infusion<br>* Other names: vPDT;Drug: Sham Ranibizumab<br>* Empty vial to mimic the intravitreal injection<br>Drug: Sham verteporfin PDT<br>* Sham vPDT intravenous infusion of dextrose 5% solution followed by light application (PDT).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average Change From Baseline to Month 1 Through Month 3 on Visual Acuity of the Study Eye | The Best Corrected Visual Acuity (BCVA) was tested using the Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuity (VA) testing protocol. VA measurements were taken in a sitting position at an initial test distance of 4 meters using ETDRS charts at baseline and compared to the average from month 1 to month 3. | Baseline, Month 1 through Month 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average Change From Baseline to Month 6 in Visual Acuity of the Study Eye | The Best Corrected Visual Acuity (BCVA) was tested using the Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuity (VA) testing protocol. VA measurements were taken in a sitting position at an initial test distance of 4 meters using ETDRS charts at baseline and month 6. The overall BCVA score was calculated using the BCVA worksheet. | Baseline and Month 6 | 
| Average Change From Baseline to Month 1 Through Month 12 in Visual Acuity of the Study Eye | The Best Corrected Visual Acuity (BCVA) was tested using the Early Treatment Diabetic Retinopathy Study (ETDRS) Visual Acuity (VA) testing protocol. VA measurements were taken in a sitting position at an initial test distance of 4 meters using ETDRS charts at baseline and Month 1 through 12 | Baseline and Month 1 through Month 12 | 
| Percentage of Patients With Best Corrected Visual Acuity (BCVA) ≥10 and ≥15 Letters Gain or Reach 84 Letters at Month 3 | 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 more than 10 or more than 15 of visual acuity at month 3. | Month 3 | 
| Percentage of Patients With Best Corrected Visual Acuity (BCVA) ≥10 and ≥15 Letters Gain or Reach 84 Letters at Month 6 and 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 increased score indicates improvement in acuity. This outcome assessed the percentage of participants who gained more than 10 or more than 15 letters of visual acuity at month 6 and month 12. | Months 6 and 12 | 
| Percentage of Patients With Best Corrected Visual Acuity (BCVA) ≥10 and ≥15 Letter Loss at Month 3 | 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 decreased score indicates worsening in acuity. This outcome assessed the percentage of participants who lost more than 10 or more than 15 of visual acuity at month 3. | Month 3 | 
| Percentage of Patients With Best Corrected Visual Acuity (BCVA) ≥10 and ≥15 Letter Loss at Month 6 and 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. A decreased score indicates worsening in acuity. This outcome assessed the percentage of participants who lost more than 10 or more than 15 of visual acuity at month 6 and 12. | Months 6 and 12 | 
| Change From Baseline in Central Retinal Thickness of the Study Eye Over Time | Retinal thickness was measured by Central Reading Center using patient's Optical Coherence Tomography (OCT) images provided by investigators. | Baseline, Month 3, Month 6 and Month 12 | 
| Percentage of Patients With Choroidal Neovascularization (CNV) Leakage in the Study Eye | CNV leakage assessment plus other choroid and retinal disorders were assessed by Central Reading Center using patient's fluorescein angiography and color fundus photography images provided by investigators. | Baseline and Month 12 | 
| Number of Ranibizumab Injections Received Prior to Month 3 | In order to describe exposure to the study drug the number of ejections was evaluated | Day 1 and prior to month 3 | 
| Number of Ranibizumab Injections Received by Patients Randomized to the Ranibizumab Groups, by Period | Number of ranibizumab injections received by patients randomized to the ranibizumab groups, by period | Day 1 prior to month 6 and prior to month 12 | 
| Number of Ranibizumab Injections Received by Patients Randomized to vPDT With Ranibizumab From Month 3 by Period | Number of ranibizumab injections received by patients randomized to the vPDT with ranibizumab groups, by period. | Month 3 up to month 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pathologic myopia, PM, choroidal neovascularization, CNV, ranibizumab, verteporfin PDT