Intravitreal Aflibercept for Neovascular Polypoidal Choroidal Vasculopathy (RIVAL Trial)

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the safety and efficacy of intravitreal aflibercept injection (IAI) in patients with neovascular polypoidal choroidal vasculopathy.

Detailed Description
-----------------
This is an open-label, non-randomized, unmasked, study of IAI in patients with choroidal neovascularization secondary to polypoidal choroidal vasculopathy (PCV). Twenty treatment naïve and previously treated PCV eyes will be enrolled (only one study eye per patient will be enrolled). A maximum of 10 previously treated eyes will be enrolled. Consented, enrolled patients will be followed monthly. All patients will receive monthly IAI 2.0 mg intravitreally for 3 months (Baseline, Months 1 and 2), followed by mandatory IAI 2.0 mg every 2 months (Months 4, 6, 8 and 10) for 12 months. Patients can receive additional IAI treatment (Months 3, 5, 7, 9, and 11) if the re-treatment criteria are met. Starting at Month 3, patients can receive non-anti vascular endothelial growth factor (VEGF) rescue therapy (ie: Photodynamic Therapy (PDT), laser, intravitreal steroids) if the pre-defined criteria are met.

Official Title
-----------------
Open-label, Non-randomized, Unmasked, Study of IAI in Patients Which Choroidal Neovascularization Secondary to Polypoidal Choroidal Vasculopathy (PCV)

Conditions
-----------------
Neovascular Polypoidal Choroidal Vasculopathy

Intervention / Treatment
-----------------
* Drug: Rescue Intravitreal Aflibercept Injection
* Procedure: Rescue Therapy with PDT, Laser or Intravitreal Steroids


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Males and females ≥ 18 years of age. Females of child bearing potential will undergo urine pregnancy testing and be required to use appropriate methods of birth control ICG and fluorescein angiographic characteristics consistent with active, leaking PCV with subfoveal lesions and/or subfoveal hemorrhage, lipid exudates, PED or fluid Best corrected early treatment of diabetic retinopathy study (ETDRS) visual acuity at 4 meters between 20/20 - 20/400 (BCVA ETDRS letter score 85 - 20 letters in the study eye) Lesion Characteristics - leaking lesions consistent with PCV. (No limitations on hemorrhage, fibrosis or atrophy) Clear ocular media to allow for photography/angiography Willing and able to comply with clinic visits and study-related procedures Patients with bilateral disease will only be able to enroll one eye Provide signed informed consent Exclusion Criteria: Any history of systemic Anti-VEGF therapy Current ocular or periocular infection Active intraocular inflammation Any comorbid condition that may decrease visual acuity Any patients who have had intraocular surgery within the past 30 days for any condition For treatment naïve patients: No prior anti-VEGF, PDT, intravitreal steroids or laser (subfoveal or non foveal) For previously-treated patients : Prior anti-VEGF (ranibizumab, bevacizumab, pegaptanib) within 30 days Prior IAI Prior PDT , transpupillary thermal therapy (TTT) or radiation within 90 days (a maximum of 3 PDTs allowed) Prior intravitreal steroids within 90 days Prior non-foveal laser within 90 days Prior subfoveal laser Patients with features of dry age-related macular degeneration such as abundant drusen and symptoms/demographic features inconsistent with the diagnosis of PCV Allergy to fluorescein, ICG, iodine, shellfish Any other condition that the investigator believes would pose a significant hazard to the patient if the investigational therapy were initiated Participation in another simultaneous medical investigation or trial History of previous subfoveal laser Advanced glaucoma (IOP > 25 or cup/disc ratio > 0.8) Pregnant or breast-feeding women Sexually active men* or women of childbearing potential** who are unwilling to practice adequate contraception during the study (adequate contraceptive measures include stable use of oral contraceptives or other prescription pharmaceutical contraceptives for 2 or more menstrual cycles prior to screening; intrauterine device (IUD); bilateral tubal ligation; vasectomy; condom plus contraceptive sponge, foam, or jelly, or diaphragm plus contraceptive sponge, foam, or jelly) *Contraception is not required for men with documented vasectomy. **Postmenopausal women must be amenorrheic for at least 12 months in order not to be considered of child bearing potential. Pregnancy testing and contraception are not required for women with documented hysterectomy or tubal ligation.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Intravitreal Aflibercept Injection<br>All patients will receive monthly IAI 2.0 mg intravitreally for 3 months (Baseline, Months 1 and 2), followed by mandatory IAI 2.0 mg every 2 months (Months 4, 6, 8 and 10) for 12 months. | Drug: Rescue Intravitreal Aflibercept Injection<br>* Patients can receive additional IAI treatment (Months 3, 5, 7, 9, and 11) if the re-treatment criteria are met.<br>Procedure: Rescue Therapy with PDT, Laser or Intravitreal Steroids<br>* Starting at Month 3, patients can receive non-anti VEGF rescue therapy (ie: PDT, laser, intravitreal steroids) if the pre-defined criteria are met.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and Severity | The primary objective of the study is the incidence and severity of ocular and systemic adverse events at Month 6. | Month 6 | 
| Incidence and Severity | The primary objective of the study is the incidence and severity of ocular and systemic adverse events at Month 12. | Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Best Corrected Visual Acuity (BCVA) | •The mean change in BCVA from Baseline to Month 6 and from Baseline up to 12 months | Months 6 and 12 | 
| Change in Best Corrected Visual Acuity (BCVA) | •Proportion of patients gaining 5, 10 and 15 letters at Months 6 and 12 | Months 6 and 12 | 
| Change in Best Corrected Visual Acuity (BCVA) | •Proportion of patients losing 5,10, and 15 letters at Months 6 and 12 | Months 6 and 12 | 
| Photography Assessments | •Mean change from baseline in central subfield thickness at Months 6 and 12 as assessed on spectral domain optical coherence tomography (SD-OCT) | Months 6 and 12 | 
| Photography Assessments | •Mean change from baseline in macular volume at Months 6 and 12 as assessed on SD-OCT | Months 6 and 12 | 
| Photography Assessments | •Mean change from baseline in choroidal thickness at Months 6 and 12 through SD-OCT | Months 6 and 12 | 
| Photography Assessments | •Proportion of patients with no evidence of pigment epithelial detachment (PED), intraretinal and subretinal fluid from choroidal neovascularization (CNV) as assessed by optical coherence tomography (OCT) at 6 and 12 months | Months 6 and 12 | 
| Photography Assessments | •Mean change from baseline in the total area of CNV fluorescein angiographic leakage at months 6 and 12 | Months 6 and 12 | 
| Photography Assessments | •Fluorescein angiograms, indocyanine green (ICG) angiograms, OCT and fundus photographs at Months 6 and 12 compared to baseline as unchanged, resolved, improved, worsened, or cannot determine. See section 9.1.2.2 | Months 6 and 12 | 
| Photography Assessments | •Rate of polyp regression and resolution at 6 and 12 Months | Months 6 and 12 |