Prophylactic Ranibizumab for Exudative Age-related Macular Degeneration (PREVENT)

Prophylactic Ranibizumab for Exudative Age-related Macular Degeneration (AMD) in Vulnerable Eyes With Nonexudative AMD Trial: A Multicenter, Prospectively Randomized, Masked and Controlled, Interventional Investigator Sponsored Phase I/II Study

This study will determine whether quarterly injections of Ranibizumab may prevent eyes with dry age-related macular degeneration from progressing to wet age-related macular degeneration (AMD).

Study Overview

• Status: Completed
• Conditions: Age-related Macular Degeneration
• Intervention / Treatment: Drug: Ranibizumab 0.5mg

Detailed Description

This is a multicenter, prospectively randomized, masked and controlled, interventional investigator sponsored phase I/II study of subjects with high-risk nonexudative age-related macular degeneration (AMD) treated with intravitreal ranibizumab quarterly for prophylaxis of conversion to exudative age-related macular degeneration.

The objective of this study is to investigate the safety and efficacy of prophylactic anti-vascular endothelial growth factor (VEGF) therapy with ranibizumab to prevent the development of exudative AMD in eyes with high-risk nonexudative AMD. In addition, baseline characteristics of high-risk eyes (fundus features, optical coherence tomography (OCT) parameters and genetic profile) will be evaluated to determine their predictive value in conversion to exudative AMD. The effect of ranibizumab on the atrophic component of AMD will also be monitored.

• Study Type: Interventional
• Enrollment (Actual): 108
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Mountain View, California, United States, 94040
      • Northern California Retina Vitreous Associates
    • Palm Desert, California, United States, 92211
      • Southern California Desert Retina Consultants
  • Maryland
    • Baltimore, Maryland, United States, 21237
      • Elman Retina
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Black Hills Regional Eye Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult over 50 years old
• Able to sign informed consent and comply with the study protocol for the duration of two years
• Nonexudative age-related macular degeneration (AMD) in one eye (study eye)
• History of exudative AMD in one eye only (fellow eye) diagnosed within 5 years of study enrollment

Exclusion Criteria:

• Participation in another simultaneous medical investigation or clinical trial
• Patient is pregnant, lactating, or premenopausal and not using adequate contraception
• Known serious allergies to ranibizumab, fluorescein dye, drugs for pupillary dilation, topical anesthetic, sterilizing solution (e.g. Betadine solution)
• Presence of ocular conditions with increased risk of choroidal neovascularization (CNVM) or pigment epithelial detachment (PED), including presumed ocular histoplasmosis syndrome (POHS), traumatic choroidal rupture, angioid streaks, pathologic myopia (spherical equivalent of ≥ -8 diopters or axial length of ≥ 25 mm), multifocal choroiditis, macular choroidal nevus, polypoidal choroidal vasculopathy (PCV), idiopathic central serous chorioretinopathy (ICSC), etc.
• History of vitrectomy in the study eye
• History of cataract surgery within 3 months of enrollment
• History of yttrium aluminum garnet (YAG) capsulotomy within 1 month of enrollment
• History of intraocular or periocular corticosteroid therapy within the past 90 days
• History of therapeutic radiation in the region of the study eye.
• Presence of media opacity that would preclude adequate examination and/or imaging
• Concurrent macular conditions that would affect the study parameters (epiretinal membrane, macular hole, macular edema) or require treatment within the duration of the study
• Any progressive ocular condition (uncontrolled glaucoma, diabetic retinopathy, uveitis) that may affect the visual acuity for the duration of the study
• Active ocular infection (i.e., bacterial, viral, parasitic, or fungal) in either eye at enrollment
• Presence of any advanced systemic condition that may hinder the patients participation and completion of the study
• Concurrent use of systemic anti-VEGF therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Sham; Sham Injection
Active Comparator: Quarterly Ranibizumab 0.5mg; Quarterly intravitreal injection of 0.5mg ranibizumab	Drug: Ranibizumab 0.5mg; Other Names: Lucentis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Development of exudative AMD	Development of choroidal neovascularization (conversion) defined by the presence of leakage on fluorescein angiography (FA) and fluid within or below the retina or below the retinal pigment epithelium seen on spectral-domain optical coherence tomography (SD-OCT)	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vision change	Change in best-corrected visual acuity (BCVA) from baseline at 12 and 24 months	2 years
Vision loss	Proportion of eyes losing < 5, 10, and 15 letters on EDTRS chart at 12 and 24 months	2 years
Number of injections	Number of injections required in eyes that convert from dry to wet AMD during the study period	2 years
Baseline predictive factors	Baseline demographic, genetic and ocular characteristics predictive of development of wet AMD	2 years
Development of geographic atrophy (GA)	Development of geographic atrophy (GA) as detected by fundus photography (FP) and/or fundus autofluorescence (AF).	2 years
Ocular adverse events	Incidence and severity of ocular adverse events, as identified by eye examination and imaging	2 years
Systemic adverse events	Incidence and severity of other adverse events, as identified by physical examination or subject reporting.	2 years

Collaborators and Investigators

• Sponsor: Southern California Desert Retina Consultants, MC
• Investigators: Principal Investigator: Maziar Lalezary, MD, Southern California Desert Retina Consultants

Study record dates

Study Major Dates

• Study Start (Actual): September 17, 2014
• Primary Completion (Actual): July 9, 2020
• Study Completion (Actual): July 9, 2020

Study Registration Dates

• First Submitted: April 25, 2014
• First Submitted That Met QC Criteria: May 14, 2014
• First Posted (Estimate): May 16, 2014

Study Record Updates

• Last Update Posted (Actual): August 25, 2022
• Last Update Submitted That Met QC Criteria: August 23, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: anti-VEGF; age-related macular degeneration; ranibizumab; amd; non-exudative macular degeneration; exudative macular degeneration
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Ranibizumab
• Other Study ID Numbers: ML29258