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

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

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.

Study Overview

• Status: Completed
• Conditions: Polypoidal Choroidal Vasculopathy; PCV
• Intervention / Treatment: Drug: high-dose ranibizumab; Drug: ranibizumab

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Hawaii
    • 'Aiea, Hawaii, United States, 96701
      • Retina Consultants of Hawaii
    • 'Aiea, Hawaii, United States, 96701
      • The Retina Center at Pali Momi
    • Honolulu, Hawaii, United States, 96817
      • Retina Consultants of Hawaii

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 23 years to 93 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Hawaii Pacific Health
• Collaborators: Genentech, Inc.
• Investigators: Principal Investigator: Gregg T Kokame, MD, MMM, Hawaii Pacific Health

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (Actual): August 1, 2014
• Study Completion (Actual): August 1, 2014

Study Registration Dates

• First Submitted: June 1, 2012
• First Submitted That Met QC Criteria: June 20, 2013
• First Posted (Estimate): June 24, 2013

Study Record Updates

• Last Update Posted (Actual): October 9, 2017
• Last Update Submitted That Met QC Criteria: September 8, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: Polypoidal Choroidal Vasculopathy; PCV; PEARL2
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Ranibizumab
• Other Study ID Numbers: FVF4929S