Wet AMD Recurrence Rate in Patients Stable on Three Month Ranibizumab Dosing

NCT ID: NCT01453920

Last Updated: 2012-08-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-11-30
• Study Completion Date: 2012-07-31

Brief Summary

The current norm in clinical practice for the treatment of choroidal neovascular membranes (CNVM) secondary to Age-related Macular Degeneration(AMD) involves monthly injections of Ranibizumab until the disease is stabilized. At this point, most physicians tend to follow one of two treatment regimens. 'Treat -and-observe' entails regular follow-up of stable patients, with treatment thereafter only in the presence of disease recurrence. Alternatively, in a 'treat-and-extend' dosing strategy, intervals between treatments are extended as long as disease remains stable. Many clinicians, who employ a treat-and-extend dosing regimen, do not extend their treatment intervals beyond 3 months. However, it is possible that the subgroup of patients on every three months 'treat-and-extend' dosing may represent a uniquely, stable population that would perform particularly well on an observational regimen with regular follow-up. We hypothesize that there will be a low CNVM recurrence rate in wet AMD patients stable on every three months Ranibizumab dosing ('treat-and-extend'), who begin a treat-and-observe protocol.

Detailed Description

In North America, AMD is the leading cause of irreversible vision loss in those over 65 years of age.1 Vascular endothelial growth factor A (VEGF-A) is a potent promoter of angiogenesis and vascular permeability and its role in the pathogenesis of neovascular AMD is well recognized.2,3 The advent of VEGF inhibitors such Ranibizumab (Lucentis; Genentech Inc.) has revolutionized the management of neovascular AMD. Ranibizumab is an intravitreally administered recombinant, humanized, monoclonal antibody antigen-binding fragment (Fab) that neutralizes all known active forms of VEGF-A. In the landmark phase III clinical studies MARINA, and ANCHOR, Ranibizumab injections were administered monthly over the course of 2 years to eyes with subfoveal CNVMs secondary to AMD. Ranibizumab was shown to not only prevent loss of visual acuity (VA) but also improve VA on average in these patients. 4-6

Despite the tremendous benefit of this treatment, the prospect of indefinitely adhering to the monthly treatment schedules of MARINA and ANCHOR has raised ocular and systemic safety concerns as well as convenience and cost issues for patient and physician alike. The identification of alternative dosing strategies capable of reducing the number of required anti-VEGF injections while still achieving favourable visual acuity outcomes has since been a subject of great interest. The current norm in clinical practice with Ranibizumab is to implement an 'initiation phase' followed by an individualized 'maintenance phase' that is modeled after one of two basic approaches: 'treat-and-observe' or 'treat-and-extend'. Both regimens are currently considered within the standard of clinical practice. 'Treat -and-observe' entails treatment and follow-up until the macula is free of exudation, with treatment thereafter only in the presence of recurrent exudation.7 Alternatively, in a treat-and-extend dosing strategy, intervals between treatments are extended as long as the macula remains dry.8 In the 2009 ASRS survey, 56% of physicians reported employing treat-and-observe and 44% reported employing treat-and-extend for their patients with neovascular AMD.9 In a study by Oubraham et al10 it was found that a treat-and-extend dosing regimen may yield greater gains in vision than treat-and-observe, albeit with a greater number of required injections.

In a treat-and-extend dosing strategy, some patients may require frequent monthly injections to stabilize their disease, while others may demonstrate a more stable condition requiring infrequent treatments. Many clinicians who employ a treat-and-extend dosing regimen, do not extend their treatment intervals beyond 3 months. However, it is possible that the subgroup of patients on every three months 'treat-and-extend' dosing may represent a unique, stable population that would perform particularly well on a 'treat-and-observe' regimen.

Conditions

Age Related Macular Degeneration

Keywords

Age Related Macular Degeneration; Choroidal Neovascular Membrane

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treat-and-extend

Ranibizumab injection every 3 months, with follow-up assessments at each visit (every 3 months)

Group Type: ACTIVE_COMPARATOR

Ranibizumab

Intervention Type: DRUG

Intravitreal Ranibizumab 0.05cc (10mg/ml)

Treat-and-observe'

No injection, follow-up assessments every month

Group Type: EXPERIMENTAL

Ranibizumab

Intervention Type: DRUG

Intravitreal Ranibizumab 0.05cc (10mg/ml)

Interventions

Ranibizumab

Intravitreal Ranibizumab 0.05cc (10mg/ml)

Intervention Type: DRUG

Ranibizumab

Intravitreal Ranibizumab 0.05cc (10mg/ml)

Intervention Type: DRUG

Other Intervention Names

Lucentis; Lucentis

Eligibility Criteria

Inclusion Criteria

• Age 50 years or more
• Active primary or recurrent choroidal neovascularization secondary to AMD in the study eye, currently stable on an 'every three month' treatment regimen (established using a treat and extend dosing protocol)
• Best-corrected visual acuity of Counting Fingers or better (Snellen equivalent) in the study eye
• All IVFA lesion types and lesion sizes
• One eye per subject (the "study eye"). If both eyes are eligible, the one with better VA will be selected unless, for medical reasons, the other is more appropriate

Exclusion Criteria

• Treatment of the current choroidal neovascular membrane with verteporfin photodynamic therapy (PDT), external-beam radiation therapy, transpupillary thermotherapy, or subfoveal laser photocoagulation (or juxtafoveal or extrafoveal laser photocoagulation
• History of vitrectomy surgery in the study eye
• Individuals with choroidal neovascularization from causes other than AMD

• Minimum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Health Network, Toronto

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael H Brent, MD FRCSC

Role: PRINCIPAL_INVESTIGATOR

University Health Network, Toronto

Locations

Toronto Western Hospital

Toronto, Ontario, Canada

Countries

Canada

Other Identifiers

11-0686-AE

Identifier Type: -

Identifier Source: org_study_id