Investigator Sponsored Trial of Polypoidal Choroidal Vasculopathy (PCV) Evaluation Assessing High-Dose Ranibizumab Prospectively (PEARL2)

Study Overview
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Brief Summary
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This is a 24-month study of ranibizumab (2.0 mg and 1.0 mg) in subjects with polypoidal choroidal vasculopathy as diagnosed by fluorescein/indocyanine green (FA/ICG) angiography.

Official Title
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Investigator Sponsored Trial of Polypoidal Choroidal Vasculopathy (PCV) Evaluation Assessing High-Dose Ranibizumab Prospectively

Conditions
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PCV, Polypoidal Choroidal Vasculopathy

Intervention / Treatment
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* Drug: high-dose ranibizumab
* Drug: ranibizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ability to provide written informed consent and comply with study assessments for the full duration of the study Age > 25 years Polypoidal choroidal vasculopathy as noted on fluorescein and ICG angiography: active leakage, active bleeding or recent decrease in vision BCVA using ETDRS of 20/32 to 20/400 Exclusion Criteria: Any history of previous vitrectomy Any prior treatment with verteporfin photodynamic therapy in the study eye. Previous cataract surgery within the preceding 2 months of Day 0 Active intraocular inflammation in the study eye Active infectious conjunctivitis, keratitis, scleritis, or endophthalmitis in either eye A condition that, in the opinion of the investigator, would preclude participation in the study (e.g., unstable medical status including blood pressure, cardiovascular disease) Participation in an investigational trial within 30 days of randomization that involved treatment with any drug that has not received regulatory approval at the time of study entry. Prior anti-vascular endothelial growth factor (VEGF) (Macugen, Avastin, Lucentis) in the study eye prior within 30 days prior to enrollment in this study Known allergy to any component of the study drug Blood pressure >180/110 (systolic above 180 or diastolic above 110) If blood pressure if brought below 180/110 by anti-hypertensive treatment, the patient can become eligible. Major surgery within 28 days prior to randomization or major surgery planned within the next 12 months. Major surgery is defined as a surgical procedure that is more extensive than needle biopsy/aspiration placement of a central venous access device, removal/biopsy of a skin lesion, or placement of a peripheral venous catheter. Myocardial infraction, other cardiac event requiring hospitalization, stroke, transient ischemic attack, or treatment for acute congestive heart failure within 6 months prior to randomization. Systemic anti-VEGF or pro-VEGF treatment within 3 months prior to randomization. History of recurrent significant infections or bacterial infections Pregnancy (positive pregnancy test) or lactation Premenopausal women not using adequate contraception. The following are considered effective means of contraception, surgical sterilization or use of oral contraceptives, barrier contraception with either a condom or diaphragm in conjunction with spermicide gel, an intra uterine device (IUD), or contraceptive hormone implant or patch Prior enrollment in the study Any other condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated Participation in another simultaneous medical investigation or trial.

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 95 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Cohort 1<br>12 monthly, intravitreal injections of 2.0mg ranibizumab followed by 12 monthly, intravitreal injections of 1.0mg ranibizumab | Drug: high-dose ranibizumab<br>* 20mg ranibizumab vials, 0.05ml injected intravitreally, monthly<br>Drug: ranibizumab<br>* 3 mg ranibizumab, liquid, vials, 0.1ml injected intravitreally monthly<br>* Other names: Lucentis;|
| Active Comparator: Cohort 2<br>6-months of monthly, intravitreal injections of ranibizumab 2.0mg followed by 18 months of monthly, intravitreal injections of ranibizumab 1.0mg | Drug: high-dose ranibizumab<br>* 20mg ranibizumab vials, 0.05ml injected intravitreally, monthly<br>Drug: ranibizumab<br>* 3 mg ranibizumab, liquid, vials, 0.1ml injected intravitreally monthly<br>* Other names: Lucentis;|
| Active Comparator: Cohort 3<br>24 months of monthly, intravitreal injections of ranibizumab 1.0mg | Drug: ranibizumab<br>* 3 mg ranibizumab, liquid, vials, 0.1ml injected intravitreally monthly<br>* Other names: Lucentis;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| BCVA | Mean change in best corrected visual acuity (BCVA), as assessed by the number of letters read correctly on the Early Treatment Diabetic Retinopathy Study (ETDRS) eye chart at a starting test distance of 4 meters from Baseline to Month 12. | From Baseline to Month 12 | 
| BCVA | Mean change in best corrected visual acuity (BCVA), as assessed by the number of letters read correctly on the ETDRS eye chart at a starting test distance of 4 meters from Baseline to Month 24 | Baseline to M24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ocular Adverse Events (AE) | Incidence and severity of ocular adverse events, as identified by eye examination (including visual acuity testing) | Monthly | 
| Systemic AEs | Incidence and severity of other adverse events, as identified by physical examination, subject reporting, and changes in vital signs | Monthly | 
| BCVA | Best corrected visual acuity (BCVA), as assessed by the number of letters read correctly on the ETDRS eye chart at a starting test distance of 4 meters, at Baseline, Day 14, Month 1, Month 3, Month 6, Month 9 , Month 12, Month 15, Month 18, Month 21 and Month 24 | at Baseline, Day 14, Month 1, Month 3, Month 6, Month 9 , Month 12, Month 15, Month 18, Month 21 and Month 24 | 
| Macular Edema | Optical Coherence Tomography (OCT) central macular and peripapillary thickness | Baseline, Day 14, Month 1-24 | 
| PCV Anatomic Changes | Decrease and/or resolution in the branching vascular network of the PCV complex as measured by mean size of the branched vascular network (BVN) on ICG and fluorescein angiography Decrease and/or resolution of the polyps of the PCV complex as measured on ICG and fluorescein angiography | Baseline, Months 6, 12, 24 | 
| Fundus Clinical Findings | Decrease in subretinal hemorrhage or exudates as measured by mean size as noted on fundus photography and clinic exam | Baseline, Months 6, 12, 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Polypoidal Choroidal Vasculopathy, PEARL2, PCV