GEFAL: French Evaluation Group Avastin Versus Lucentis

Sponsor

Hospices Civils de Lyon (Other)

Overall Status

Completed

CT.gov ID

NCT01170767

Collaborator

(none)

501

Enrollment

Location

Arms

Duration (Months)

11.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Age Related Macular Degeneration (AMD) is the first cause of visual impairment in elderly patients in industrialized countries. Neovascular or "wet" AMD, characterized by the presence of choroïdal neovessels, represents the most aggressive form of the disease. Its prevalence is 3.3% among patients older than 65 years in Europe, and increases with age.

Intraocular injections of anti-angiogenic monoclonal antibodies (ranibizumab) to treat AMD have appeared recently. It is derived from a larger sized molecule, bevacizumab, which do not have the market authorization for this indication. However, numerous publications of case series seem to show the effectiveness and a satisfactory safety profile of bevacizumab.

These conclusions have to be confirmed with a high level of evidence study. The aim of the GEFAL study is to demonstrate non-inferiority of effectiveness in clinical terms after 12 months of treatment with bevacizumab compared to ranibizumab on the visual acuity of patients affected by neovascular AMD.

Condition or Disease	Intervention/Treatment	Phase
Age Related Macular Degeneration	Drug: Avastin Drug: Lucentis	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

501 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

French Evaluation Group Avastin Versus Lucentis

Study Start Date :

Jun 1, 2009

Actual Primary Completion Date :

Dec 1, 2012

Actual Study Completion Date :

Dec 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Avastin intravitreal injection of bevacizumab	Drug: Avastin Intravitreal injection of bevacizumab at a concentration of 1.25 mg per injection. One injection per month at the maximum and between 3 and 12 injection in the whole study.
Active Comparator: Lucentis intravitreal injection of ranibizumab	Drug: Lucentis Intravitreal injection of ranibizumab at a concentration of 0.50 mg per injection. One injection per month at the maximum and between 3 and 12 injection in the whole study.

Arm

Intervention/Treatment

Experimental: Avastin

intravitreal injection of bevacizumab

Drug: Avastin

Intravitreal injection of bevacizumab at a concentration of 1.25 mg per injection. One injection per month at the maximum and between 3 and 12 injection in the whole study.

Active Comparator: Lucentis

intravitreal injection of ranibizumab

Drug: Lucentis

Intravitreal injection of ranibizumab at a concentration of 0.50 mg per injection. One injection per month at the maximum and between 3 and 12 injection in the whole study.

Outcome Measures

Primary Outcome Measures

Evaluation of the mean change from inclusion to 12 months post initiation of treatment in VA score, measured on the "Early Treatment Diabetic Retinopathy Study" (ETDRS) scale at an initial distance of 4 meters. [12 months]

Secondary Outcome Measures

Evaluate and compare the efficacy of treatments by bevacizumab and ranibizumab [12 months]
Evaluate and compare the proportion of adverse events occurring at the local and systemic level in the two groups. [12 months]
Describe and compare the dosage regimen (average number of injections and time before re-injection) in the two groups [12 months]
Describe the pharmacokinetic profile of the drugs in blood and aqueous humor in a sub-group of 20 patients, during the induction stage. [3 months]
Create a medico-economic model of the impact related to the two strategies. [12 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age ≥ 50 years old
Affected by neovascular retrofoveal AMD whatever the subtype, unilateral or bilateral (the eye included will be chosen by the investigator and the patient);
Best corrected VA for the studied eye ranging between 20/32 (6.3/10) and 20/320 (0.6/10) with ETDRS scale
Size of lesion < 12 disk area
In case of occult neovessels, proof required of recent development of the lesion: loss of VA of at least 5 letters ETDRS (equivalent one line) in the last 3 months OR appearance of a subretinal heamorrhage OR increase in the size of the lesion (> 10%) using fluoresceinic angiography during the last month by comparison with the last 3 months OR appearance of OCT criteria of macular oedema type, serous separation of neuro-epithelium, separation of the pigmented epithelial during the last month
Effective birth control for sexually active female
Signed informed consent.

Exclusion Criteria:

Previous or actual treatment with intravitreal injection of an anti-VEGF drug (ranibizumab, bevacizumab or pegaptanib) in the studied eye
Other healing treatment in the studied eye during the last 3 months before the first injection
Medical history of photocoagulation in the studied eye
Involvement in another clinical study (studied eye and/or the other eye)
Subretinal haemorrhage reaching the fovea centre, with a size > 50% of the lesion area
Fibrosis or retrofoveal retinal atrophy in the studied eye
Retinal pigment epithelial tear reaching the macula in the studied eye
Choroidal neovascularisation not related to a DMLA in the studied eye
Medical history of intravitreal medical device in the studied eye
Active or suspected ocular or peri-ocular infection
Serious active intra-ocular inflammation in the studied eye
Medical history of auto-immune or idiopathic uveitis
Proved diabetic retinopathy
Intra-ocular pressure ≥ 25 mmHg despite two topical hypotonic treatments
Medical history of intra-ocular surgery within 2 months before the first injection in the studied eye
Aphakia or lack of lens capsule (not removed by YAG laser) in the studied eye
Any illness or ocular condition that would require an intra-ocular surgery in the studied eye within 12 months after the inclusion
Known hypersensitivity to ranibizumab, bevacizumab, or another drug composite of the medicinal products used; allergy to fluorescein, indocyanin green, anaesthetic eye drops
Arterial hypertension that is not controlled by an appropriate treatment
Previous or actual treatment with systemic administration of bevacizumab
Follow up not possible during 12 months
No affiliation to the French national health insurance program.