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

• ClinicalTrials.gov Identifier: NCT01884597
• Recruitment Status: Completed
• First Posted: June 24, 2013
• Results First Posted: September 11, 2017
• Last Update Posted: October 9, 2017
• Sponsor: Hawaii Pacific Health
• Collaborator: Genentech, Inc.
• Information provided by (Responsible Party): Gregg T. Kokame, MD, Hawaii Pacific Health

Study Description

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.

Condition or disease	Intervention/treatment	Phase
PCV; Polypoidal Choroidal Vasculopathy	Drug: high-dose ranibizumab; Drug: ranibizumab	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 24 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Investigator Sponsored Trial of Polypoidal Choroidal Vasculopathy (PCV) Evaluation Assessing High-Dose Ranibizumab Prospectively
• Study Start Date: November 2010
• Actual Primary Completion Date: August 2014
• Actual Study Completion Date: August 2014

Arms and Interventions

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 Name: 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 Name: 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 Name: Lucentis

Outcome Measures

Primary Outcome Measures :

1. BCVA [ Time Frame: From Baseline to Month 12 ]
   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.
2. BCVA [ Time Frame: 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 :

1. Ocular Adverse Events (AE) [ Time Frame: Monthly ]
   Incidence and severity of ocular adverse events, as identified by eye examination (including visual acuity testing)
2. Systemic AEs [ Time Frame: Monthly ]
   Incidence and severity of other adverse events, as identified by physical examination, subject reporting, and changes in vital signs
3. BCVA [ Time Frame: 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
4. Macular Edema [ Time Frame: Baseline, Day 14, Month 1-24 ]
   Optical Coherence Tomography (OCT) central macular and peripapillary thickness
5. PCV Anatomic Changes [ Time Frame: 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

6. Fundus Clinical Findings [ Time Frame: Baseline, Months 6, 12, 24 ]
   Decrease in subretinal hemorrhage or exudates as measured by mean size as noted on fundus photography and clinic exam

Eligibility Criteria

• Ages Eligible for Study: 25 Years to 95 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, Hawaii

Retina Consultants of Hawaii

'Aiea, Hawaii, United States, 96701

The Retina Center at Pali Momi

'Aiea, Hawaii, United States, 96701

Retina Consultants of Hawaii

Honolulu, Hawaii, United States, 96817

Sponsors and Collaborators

Hawaii Pacific Health

Genentech, Inc.

Investigators

• Principal Investigator: Gregg T Kokame, MD, MMM; Hawaii Pacific Health

More Information

• Responsible Party: Gregg T. Kokame, MD, Medical Director, The Retina Center at Pali Momi, Hawaii Pacific Health
• ClinicalTrials.gov Identifier: NCT01884597
• Other Study ID Numbers: FVF4929S
• First Posted: June 24, 2013
• Results First Posted: September 11, 2017
• Last Update Posted: October 9, 2017
• Last Verified: September 2017

Keywords provided by Gregg T. Kokame, MD, Hawaii Pacific Health:

PEARL2; PCV; Polypoidal Choroidal Vasculopathy

Additional relevant MeSH terms:

Vascular Diseases; Cardiovascular Diseases; Ranibizumab; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Growth Inhibitors; Antineoplastic Agents