Visual Outcome in Patients With Symptomatic Macular Polypoidal Choroidal Vasculopathy (PCV) Treated With Either Ranibizumab as Monotherapy or Combined With Verteporfin Photodynamic Therapy (vPDT)

Study Overview
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Brief Summary
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This study compared the effect of ranibizumab administered as monotherapy versus ranibizumab administered in combination with verteporfin photodynamic therapy (PDT) on visual acuity in patients with symptomatic macular polypoidal choroidal vasculopathy (PCV). The results of this study provided long-term safety and efficacy data used to generate further guidance on the management of patients with PCV.

Detailed Description
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Patients were randomized to the study in 2 treatment groups: ranibizumab + vPDT combination therapy, and ranibizumab monotherapy. Based on the results of the primary analysis at Month 12, patients still in the ranibizumab monotherapy group at the time of the switch cut-off time point were switched to the ranibizumab + vPDT combination therapy group until study exit. A total of 168 and 154 patients were included in the ranibizumab + vPDT combined therapy and ranibizumab monotherapy groups, respectively for the FAS (Month 12 analysis). However, the safety set included 172 and 149 patients, respectively. Four patients in the combination therapy group never took vPDT . Among them, 1 patient actually received verteporfin injection but no laser injection. Thus a total of 3 patients (4-1) in the combination therapy group did not take the actual full vPDT treatment. Additionally, 7 patients in the monotherapy group received vPDT and 1 patient from the monotherapy group did not receive ranibizumab treatment. Considering the above numbers, safety set included 172 patients (i.e., 168-3+7) in the ranibizumab + vPDT combination therapy group and 149 patients (i.e., 154-7+3-1) in the ranibizumab monotherapy group for Month 12 analysis. For the Month 24 safety analysis, the 14 patients in the ranibizumab monotherapy group who were switched to ranibizumab +vPDT combination therapy group were analyzed as a separate group, ie, ranibizumab 0.5 mg + vPDT (switched). .

Official Title
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A 24-month, Phase IV, Randomized, Double Masked, Multi-center Study of Ranibizumab Monotherapy or Ranibizumab in Combination With Verteporfin Photodynamic Therapy on Visual Outcome in Patients With Symptomatic Macular Polypoidal Choroidal Vasculopathy

Conditions
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Age-related Macular Degeneration, Polypoidal Choroidal Vasculopathy

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed diagnosis of symptomatic macular PCV in the study eye A qualifying vision score at study entry A qualifying lesion size in the study eye at study entry Exclusion Criteria: Active inflammation or infection in the study eye Uncontrolled intraocular pressure in the stuy eye Ocular condition in the study eye which may impact vision and confound study outcomes Prior treatment of the study eye with anti-VEGF therapy, verteporfin PDT, other laser and surgical interventions, intraocular corticosteroids

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ranibizumab + vPDT<br>Treatment initiation with Ranibizumab and verteporfin PDT (vPDT), with re-treatment need (either Ranibizumab alone or combined with vPDT) determined at monthly visits based on defined retreatment criteria | Drug: Ranibizumab<br>* Intravitreal injection of 0.5 mg ranibizumab<br>* Other names: Lucentis;Drug: Verteporfin PDT<br>* Infusion of 30 ml verteporfin in 5% dextrose solution followed by 83 sec of laser light (50J/cm2; 600mW/cm2; 689 nm)<br>|
| Active Comparator: Ranibizumab monotherapy<br>Treatment initiation with Ranibizumab and Sham PDT, with re-treatment need (either Ranibizumab alone or combined with Sham PDT) determined at monthly visits based on defined retreatment criteria | Drug: Ranibizumab<br>* Intravitreal injection of 0.5 mg ranibizumab<br>* Other names: Lucentis;Drug: Sham PDT<br>* Infusion of 30 ml 5% dextrose solution followed by 83 sec of laser light (50J/cm2; 600mW/cm2; 689 nm)<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) at Month 12 - Study Eye | Best Corrected Visual Acuity (BCVA) was assessed during all study visits using best correction determined from protocol refraction at a starting test distance of 4 meters. VA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts. The BCVA score is the number of letters read correctly by the patient, hence an increase in score indicates improvement in acuity. | Baseline, Month 12 | 
| Number of Patients With Complete Polyp Regression From Baseline at Month 12 - Study Eye | Polyp regression was based on the Indocyanine green angiography (ICGA) assessment by the Central Reading Center (CRC). A patient was considered to have complete polyp regression if the presence of polyps, as assessed by CRC, had value No. Polyp regression which may lead to disease stabilization and consequently better vision. | Baseline, Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in Best-Corrected Visual Acuity (BCVA) at Month 24 - Study Eye | Best Corrected Visual Acuity (BCVA) was assessed during all study visits using best correction determined from protocol refraction at a starting test distance of 4 meters. VA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at a starting test distance of 4 meters. The BCVA score is the number of letters read correctly by the patient, hence an increase in score indicates improvement in acuity. | Baseline, Month 24 | 
| Percentage of Patients With BCVA (Letters) Change From Baseline at Month 24 - Study Eye | 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. | Baseline, Month 24 | 
| Maintenance of BCVA (Within 5 Letter Change) at Month 12 and 24 Compared to BCVA at the Time Point of First Ranibizumab Treatment Interruption | Best Corrected Visual Acuity (BCVA) was assessed using best correction determined from protocol refraction at a starting test distance of 4 meters. VA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at a starting test distance of 4 meters. | Month 3, Month 12, Month 24 | 
| Change in BCVA at Month 12 and 24 Compared to the Time Point of First Ranibizumab Treatment Interruption | Best Corrected Visual Acuity (BCVA) was assessed using best correction determined from protocol refraction at a starting test distance of 4 meters. VA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at a starting test distance of 4 meters. | Month 3, Month 12, Month 24 | 
| Percentage of Patients With Complete Polyp Regression at Months 6 and 24 - Study Eye | Polyp regression was based on the Indocyanine green angiography (ICGA) assessment by the Central Reading Center (CRC). A patient was considered to have complete polyp regression if the presence of polyps, as assessed by CRC, had value No. Polyp regression which may lead to disease stabilization and consequently better vision. | Month 6, Month 24 | 
| Percentage of Patients With Presence of Leakage at Month 6, Month 12 and Month 24 - Study Eye | Presence of lesion leakage was based on Fluorescein Angiography (FA) as assessed by the Central Reading Center (CRC). The presence of leakage may lead to disease progression and worsening vision. | Month 6, Month 12 and Month 24 | 
| Mean Change From Baseline in Investigator-Assessed Central Subfield Retinal Thickness (CSFT) at Month 24 - Study Eye | The thickness of the retina was measured using Spectral Domain (SD) optical coherence tomography (OCT) equipment (SD-OCT) and reported as a difference, in micrometers. A negative number indicates a reduction in thickness, whereas a positive number indicates an increase. An increase in thickness may indicate a progression of the underlying disease. | Baseline, Month 24 | 
| Total Number of Ranibizumab Injections Received in the Study Eye Prior to Month 12 |  | Baseline, Month 12 | 
| Total Number of Verteporfin/Sham PDT Injections Received in the Study Eye Prior to Month 12 |  | Baseline, Month 12 | 
| Total Number of Ranibizumab Injections Received in the Study Eye Prior to Month 24 |  | Baseline, Month 24 | 
| Total Number of Verteporfin/Sham PDT Injections Received in the Study Eye Prior to Month 24 |  | Baseline, Month 24 | 
| Total Number of Ranibizumab Injections Received in the Study Eye From Month 3 to Month 12 |  | Month 3, Month 12 | 
| Total Number of Ranibizumab Injections Received in the Study Eye From Month 3 to Month 24 |  | Month 3, Month 24 | 
| Mean Change From Baseline in Composite Scores, National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25) at Months 3, 12 and 24 | The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) was used to measure a patient's subjective assessment of vision-related quality of life at Months 3, 12 and 24. The 12 subscales in the VFQ-25 are general health, general vision, ocular pain, near activities, distance activities, social function, mental health, role difficulties, dependency, driving, color vision, and peripheral vision. The scores on the subscales were added together for a total score, which ranged from 0 to 100. A higher score indicated poorer function. | Baseline, Month 3, Month 12, Month 24 | 
| Number of Ocular Adverse Events of the Study Eye Regardless of Study Drug Relationship up to Month 24, Any Primary System Organ Class | Reported categorically: Mild, Moderate, Severe | Up to Month 24 | 
| Number of Non-Ocular Adverse Events of the Study Eye Regardless of Study Drug Relationship up to Month 24, Any Primary System Organ Class | Reported categorically: Mild, Moderate, Severe | Up to Month 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Polypoidal choroidal vasculopathy, Visual acuity, Ranibizumab, Verteporfin PDT