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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University Health Network, Toronto
ClinicalTrials.gov Identifier:
NCT01453920
First received: October 13, 2011
Last updated: August 27, 2012
Last verified: August 2012

October 13, 2011
August 27, 2012
November 2011
July 2012   (final data collection date for primary outcome measure)
Prevalence of CNVM recurrence [ Time Frame: 6 months ] [ Designated as safety issue: No ]
To determine the prevalence of CNVM recurrence in each study group as defined by visual acuity (VA), dilated fundus exmaination (DFEx), Spectral Domain Optical Coherence Tomography (SDOCT) +/- Intravenous Flourescein Angiography (IVFA).
Same as current
Complete list of historical versions of study NCT01453920 on ClinicalTrials.gov Archive Site
  • Mean change in VA between baseline [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Proportion of patients losing > 15 letters (3 lines) from baseline [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Number of Ranibizumab injections [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Presence of subretinal and/or intraretinal fluid on SDOCT [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Central Retinal Thickness measurement on SDOCT [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Incidence of ocular and systemic adverse events [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Patient's sensitivity in subjectively detecting CNVM recurrence (gold standard for comparison, clinical presentation including DFEx, OCT, +/- IVFA) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Wet AMD Recurrence Rate in Patients Stable on Three Month Ranibizumab Dosing
Choroidal Neovascular Membrane Recurrence Rate in Wet AMD Patients Stable on Three Month Ranibizumab Dosing

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.

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.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Age Related Macular Degeneration
Drug: Ranibizumab
Intravitreal Ranibizumab 0.05cc (10mg/ml)
Other Name: Lucentis
  • Active Comparator: Treat-and-extend
    Ranibizumab injection every 3 months, with follow-up assessments at each visit (every 3 months)
    Intervention: Drug: Ranibizumab
  • Experimental: Treat-and-observe'
    No injection, follow-up assessments every month
    Intervention: Drug: Ranibizumab
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
44
July 2012
July 2012   (final data collection date for primary outcome measure)

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
Both
50 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Canada
 
NCT01453920
11-0686-AE
Yes
University Health Network, Toronto
University Health Network, Toronto
Not Provided
Principal Investigator: Michael H Brent, MD FRCSC Toronto Western Hospital - University Health Network
University Health Network, Toronto
August 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP