Aflibercept After Ranibizumab in Exudative Age-related Macular Degeneration (ARI2)

A Phase III b, Multicenter Study of the Efficacy and Safety of Aflibercept Switch in Patients With Exudative AMD With Detachment of the Retinal Pigment Epithelium and Previously Treated With Ranibizumab Intravitreal Injection. (ARI2)

The purpose of the current study is to evaluate the ability of Eylea to induce a regression of PED height on patients previously extensively treated by Lucentis.

The regimen proposed for this study is the 3 monthly injection followed by a 6 weeks interval injection until week 26.

Study Overview

• Status: Completed
• Conditions: Eye Diseases; Macular Degeneration; Retinal Degeneration; Retinal Diseases; Wet Macular Degeneration
• Intervention / Treatment: Drug: Aflibercept

Detailed Description

The regimen proposed for this study is the 3 monthly injection followed by a 6 weeks interval injection until week 26.

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Bordeaux, France, 33000
    • Hôpital Pellegrin
  • Créteil, France, 94010
    • Centre Hospitalier Intercommunal de Creteil
  • Dijon, France, 21033
    • Hôpital général de Dijon
  • Lyon, France, 69003
    • Centre d'ophtalmologie Rabelais
  • Montbonnot-Saint-Martin, France, 38330
    • Cabinet Alpes Rétine
  • Nantes, France, 44093
    • CHR Hotel Dieu
  • Paris, France, 75006
    • Centre d'explorations ophtalmologiques de l'odéon
  • Paris, France, 75012
    • Hôpital des Quinze-Vingts
  • Rouen, France, 76100
    • Clinique Mathilde

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:

• Men and women ≥ 50 years of age
• Active primary subfoveal choroidal neovascularization (CNV) lesions secondary to AMD including juxtafoveal lesions that affect the fovea evidenced by Fluorescein Angiography in the study eye
• Patient having been treated for at least 12 months with Ranibizumab (≥ 8 injections)
• Patient with a PED > 250 µm, defined by spectral domain optical coherent tomography (SD-OCT), measured at two consecutive visits before inclusion with any persisting sub retinal fluid at baseline
• Patient affiliated to a social security scheme
• Signed Informed Consent

Exclusion Criteria:

• Patient with subfoveal atrophy and/or atrophy with a diameter greater than 150µm in the subfoveal or juxtafoveal area
• Patient with a subfoveal fibrosis
• Subretinal hemorrhage that is either 50 percent or more of the total lesion area or 1 or more disc areas in size in the study eye.
• Scar, fibrosis or atrophy making up > 50% of total lesion in the study eye.
• Presence of retinal pigment epithelial tears or rips involving the macula in the study eye.
• History of any vitreous hemorrhage within 4 weeks prior to Visit 1 in the study eye.
• Presence of other causes of choroidal neovascularization, including pathologic myopia (spherical equivalent of -8 diopters or more negative, or axial length of 25mm or more), ocular histoplasmosis syndrome, angioid streaks, choroidal rupture, or multifocal choroiditis in the study eye or clinical evidence of diabetic retinopathy, diabetic macular edema or any retinal vascular disease other than AMD in either eye.
• Any history of macular hole of stage 3 and above in the study eye.
• Uncontrolled glaucoma (defined as intraocular pressure ≥25 mmHg despite treatment with antiglaucoma medication) or prior laser treatment for glaucoma in the study eye.
• Active intraocular inflammation or uveitis of scleritis or episcleritis in the study eye or ocular or periocular infection in either eye
• Presence or history of scleromalacia in the study eye.
• Aphakia or pseudophakia with absence of posterior capsule (unless it occurred as a result of a yttrium aluminum garnet (YAG) posterior capsulotomy) in the study eye.
• Previous therapeutic radiation in the study eye.
• History of corneal transplant or corneal dystrophy in the study eye.
• Significant media opacities, including cataract, in the study eye which might interfere with visual acuity, assessment of toxicity, or fundus photography.
• Any concurrent intraocular condition in the study eye (e.g. cataract) that, in the opinion of the investigator, could require either medical or surgical intervention during the 24 month study period.
• Any concurrent ocular condition in the study eye which, in the opinion of the investigator, could either increase the risk to the subject beyond what is to be expected from standard procedures of intraocular injection, or which otherwise may interfere with the injection procedure or with evaluation of efficacy or safety.
• Any systemic treatment with an investigational agent except dietary supplements or vitamins in the past 6 months prior to Day 1 for any condition.
• Any history of allergy to povidone iodine.
• Contraindications as listed
• Patient enrolled in another interventional research or not
• Patient already included in the study for the treatment of one of his eye
• Pregnant or nursing woman
• Lack of effective contraception for women of childbearing age

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Aflibercept; Patients will receive 2 mg of aflibercept by intravitreal injection every 4 weeks until week 8, followed by every 6 weeks to week 26	Drug: Aflibercept; Intravitreal Injection; Other Names: Eylea; BAY86-5321

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in maximal height of pigment epithelium detachment (PED) at 12 weeks	Baseline and 12 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in central retinal thickness by SD OCT at 12 weeks	Baseline and 12 weeks
Change from Baseline in visual acuity at 12 weeks	Baseline and 12 weeks
Change from Baseline in volume of pigment epithelium detachment at 12 weeks	Baseline and 12 weeks
Association with genes involved in AMD history	genetic testing will be performed when all the particpitants will be recruited
Number of participants with adverse events from baseline to 32 weeks	from baseline to 32 weeks
Change from Baseline in pigment epithelium detachment height at 12 weeks	Baseline and 12 weeks
Change from baseline in central retinal thickness at 32 weeks	baseline and 32 weeks
Change from Baseline in pigment epithelium detachment height at 32 weeks	Baseline and 32 weeks
Change from Baseline in visual acuity at 32 weeks	Baseline and 32 weeks
Change from Baseline in volume of pigment epithelium detachment at 32 weeks	Baseline and 32 weeks

Collaborators and Investigators

• Sponsor: Centre Hospitalier Intercommunal Creteil
• Collaborators: Bayer
• Investigators: Study Director: Eric Souied, MD, Centre Hospitalier Intersommunal de Créteil

Publications and helpful links

General Publications

• Mouallem-Beziere A, Blanco-Garavito R, Richard F, Miere A, Jung C, Rozet JM, Souied EH. GENETICS OF LARGE PIGMENT EPITHELIAL DETACHMENTS IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION. Retina. 2020 Apr;40(4):663-671. doi: 10.1097/IAE.0000000000002454.

Study record dates

Study Major Dates

• Study Start: December 1, 2013
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: March 2, 2014
• First Submitted That Met QC Criteria: June 2, 2014
• First Posted (Estimate): June 5, 2014

Study Record Updates

• Last Update Posted (Estimate): December 6, 2022
• Last Update Submitted That Met QC Criteria: December 5, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: Eye diseases; Vision Impairment and Blindness; Eyes and Vision; Seniors; Neovascular Age-Related Macular Degeneration (AMD); Retinal Disease
• Additional Relevant MeSH Terms: Eye Diseases, Hereditary; Macular Degeneration; Retinal Diseases; Eye Diseases; Wet Macular Degeneration; Retinal Degeneration; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Aflibercept
• Other Study ID Numbers: ARI2; 2013-002869-19 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No