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

Phase 1

Completed

Conditions: Polypoidal Choroidal Vasculopathy
PCV

Interventions: Drug: high-dose ranibizumab
Drug: ranibizumab

Registration Number: NCT01884597

Lead Sponsor: Hawaii Pacific Health

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 24

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 1	high-dose ranibizumab	12 monthly, intravitreal injections of 2.0mg ranibizumab followed by 12 monthly, intravitreal injections of 1.0mg ranibizumab
Cohort 2	high-dose ranibizumab	6-months of monthly, intravitreal injections of ranibizumab 2.0mg followed by 18 months of monthly, intravitreal injections of ranibizumab 1.0mg
Cohort 2	ranibizumab	6-months of monthly, intravitreal injections of ranibizumab 2.0mg followed by 18 months of monthly, intravitreal injections of ranibizumab 1.0mg
Cohort 1	ranibizumab	12 monthly, intravitreal injections of 2.0mg ranibizumab followed by 12 monthly, intravitreal injections of 1.0mg ranibizumab
Cohort 3	ranibizumab	24 months of monthly, intravitreal injections of ranibizumab 1.0mg

Primary Outcome Measures

Name	Time	Method
BCVA	Baseline to M24	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

Secondary Outcome Measures

Name	Time	Method
BCVA	at Baseline, Day 14, Month 1, Month 3, Month 6, Month 9 , Month 12, Month 15, Month 18, Month 21 and Month 24	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
Fundus Clinical Findings	Baseline, Months 6, 12, 24	Decrease in subretinal hemorrhage or exudates as measured by mean size as noted on fundus photography and clinic exam
Ocular Adverse Events (AE)	Monthly	Incidence and severity of ocular adverse events, as identified by eye examination (including visual acuity testing)
Macular Edema	Baseline, Day 14, Month 1-24	Optical Coherence Tomography (OCT) central macular and peripapillary thickness
Systemic AEs	Monthly	Incidence and severity of other adverse events, as identified by physical examination, subject reporting, and changes in vital signs
PCV Anatomic Changes	Baseline, Months 6, 12, 24	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