Managing Neovascular (Known as "Wet") Age-related Macular Degeneration Over 2 Years Using Different Treatment Schedules of 2 mg Intravitreal Aflibercept Injected in the Eye (ARIES)

Managing Neovascular Age-related Macular Degeneration (nAMD) Over 2 Years With a Treat and Extend (T&E) Regimen of 2 mg Intravitreal Aflibercept - a Randomized, Open-label, Active-controlled, Parallel-group Phase IV/IIIb Study (ARIES)

This study aims to evaluate the optimal use, efficacy, and safety of a Treat-and-Extend regimen with aflibercept in subjects with nAMD.

Study Overview

• Status: Completed
• Conditions: Macular Degeneration
• Intervention / Treatment: Drug: Eylea (Intravitreal Aflibercept, VEGF Trap-Eye, BAY86-5321); Drug: Eylea (Intravitreal Aflibercept, VEGF Trap-Eye, BAY86-5321)

Detailed Description

The T&E dosing regimen for nAMD has emerged as a preferred regimen for many treating physicians aiming at maximizing outcomes by proactively treating the subject at each visit and by extending the treatment interval (if extension criteria are met), thus limiting visits, monitoring, and injections.

To this day, there is limited evidence available addressing the question of what are useful intervals for treating and monitoring, how do they differ among subjects, and how are retreatment criteria applied to achieve long-term desirable outcomes in real-life practice. This study is designed to evaluate the optimal use, efficacy, and safety of the T&E regimen with intravitreal aflibercept in subjects with nAMD.

• Study Type: Interventional
• Enrollment (Actual): 287
• Phase: Phase 4

Contacts and Locations

Study Locations

• Australia
  • Launceston, Australia, 7249
  • New South Wales
    • Strathfield, New South Wales, Australia, 2135
    • Sydney, New South Wales, Australia, 2000
    • Westmead, New South Wales, Australia, 2145
  • Victoria
    • East Melbourne, Victoria, Australia, 3002
• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8G 5E4
    • Ottawa, Ontario, Canada, K2B7E9
  • Quebec
    • Boisbriand, Quebec, Canada, J7H1S6
• France
  • Creteil Cedex, France, 94010
  • Nice cedex 1, France, 06006
• Germany
  • Berlin, Germany, 10713
  • Baden-Württemberg
    • Freiburg, Baden-Württemberg, Germany, 79106
    • Tübingen, Baden-Württemberg, Germany, 72076
  • Niedersachsen
    • Hannover, Niedersachsen, Germany, 30625
  • Nordrhein-Westfalen
    • Bonn, Nordrhein-Westfalen, Germany, 53105
    • Köln, Nordrhein-Westfalen, Germany, 50924
  • Saarland
    • Sulzbach, Saarland, Germany, 66280
  • Sachsen
    • Chemnitz, Sachsen, Germany, 09116
• Hungary
  • Budapest, Hungary, 1115
  • Budapest, Hungary, 1125
  • Budapest, Hungary, 1062
  • Budapest, Hungary, 1085
  • Budapest, Hungary, 1106
  • Budapest, Hungary, 1133
  • Debrecen, Hungary, 4032
  • Pecs, Hungary, 7621
  • Szombathely, Hungary, 9700
• Italy
  • Lazio
    • Roma, Lazio, Italy, 00198
  • Lombardia
    • Milano, Lombardia, Italy, 20132
    • Milano, Lombardia, Italy, 20157
  • Veneto
    • Padova, Veneto, Italy, 35128
• Spain
  • Madrid, Spain
  • Zaragoza, Spain, 50009
  • Asturias
    • Oviedo, Asturias, Spain, 33012
• United Kingdom
  • Bristol, United Kingdom, BS12LX
  • Liverpool, United Kingdom, L7 8XP
  • London, United Kingdom, EC1V2PD
  • Oxford, United Kingdom, OX3 9DU
  • Kent
    • Canterbury, Kent, United Kingdom, CT1 3NG

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Men and women ≥ 50 years of age.
• Active primary subfoveal CNV lesions secondary to nAMD, including juxtafoveal lesions that affect the fovea as evidenced by FA in the study eye. Patients with polypoidal choroidal vasculopathy or retinal angiomatous proliferation are eligible to participate in the study, and their condition should be captured in the eCRF.
• ETDRS BCVA of 73 to 25 letters (20/40 to 20/320 Snellen equivalent) in the study eye.
• The area of CNV must occupy at least 50% of the total lesion.

Exclusion Criteria:

• Any prior ocular (in the study eye) or systemic treatment or surgery for nAMD, except dietary supplements or vitamins.
• Any prior or concomitant therapy with another investigational agent to treat nAMD in the study eye.
• Prior treatment with anti-VEGF agents as follows:
• Prior treatment with anti-VEGF therapy in the study eye is not allowed
• Prior treatment with anti-VEGF therapy in the fellow eye with an investigational agent (not approved, e.g. bevacizumab) within the last 3 months before the first dose in the study. Such treatment will also not be allowed during the study. Prior treatment with an approved anti-VEGF therapy in the fellow eye is allowed.
• Prior systemic anti-VEGF therapy, investigational or approved, within the last 3 months before the first dose in the study, and such treatment will not be allowed during the study.
• Total lesion size >12 disc areas (30.5 mm2, including blood, scars and neovascularization) as assessed by FA in the study eye.
• Subretinal hemorrhages that are either 50% or more of the total lesion area, or if the blood is under the fovea and is 1 or more disc areas in size in the study eye. (If the blood is under the fovea, then the fovea must be surrounded by 270 degrees by visible CNV).
• Scar or fibrosis making up >50% of the total lesion in the study eye.
• Scar, fibrosis, or atrophy involving the center of the fovea in the study eye.
• Presence of retinal pigment epithelial tears or rips involving the macula in the study eye.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Early-start T&E / Arm 1; Early-start T&E arm: test group, early treatment individualization	Drug: Eylea (Intravitreal Aflibercept, VEGF Trap-Eye, BAY86-5321); 3 monthly doses followed by individualized treatment intervals of between 8 to16 weeks based on protocol-defined anatomical criteria; Drug: Eylea (Intravitreal Aflibercept, VEGF Trap-Eye, BAY86-5321); 3 monthly doses followed by five 8-weekly doses (5 x 2Q8), then by individualized treatment intervals of between 8 to 16 weeks based on protocol-defined anatomical criteria
Active Comparator: Late-start T&E / Arm 2; Late-start T&E arm; per label, control group, treatment individualization after Year 1	Drug: Eylea (Intravitreal Aflibercept, VEGF Trap-Eye, BAY86-5321); 3 monthly doses followed by individualized treatment intervals of between 8 to16 weeks based on protocol-defined anatomical criteria; Drug: Eylea (Intravitreal Aflibercept, VEGF Trap-Eye, BAY86-5321); 3 monthly doses followed by five 8-weekly doses (5 x 2Q8), then by individualized treatment intervals of between 8 to 16 weeks based on protocol-defined anatomical criteria

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in BCVA as Measured by the ETDRS Letter Score	BCVA (best corrected visual acuity) was measured by the ETDRS (Early Treatment Diabetic Retinopathy Study) letter score of 73 to 25 (= Acuity of 20/40 to 20/320) in the study eye at 4 meters; a higher score represents better functioning.	From Week 16 to Week 104

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Maintaining Vision (<3 Lines Loss) at Week 104 Compared With Baseline	Participants maintained 3 lines (15 letters) vision loss in BCVA (Best-corrected visual acuity) as measured by the ETDRS (Early Treatment Diabetic Retinopathy Study) letter.	at Week 104
Change in BCVA From Baseline to Week 52, Baseline to Week 104, and Week 16 to Week 52	BCVA (best corrected visual acuity) was measured by the ETDRS (Early Treatment Diabetic Retinopathy Study) letter score of 73 to 25 (= Acuity of 20/40 to 20/320) in the study eye at 4 meters; a higher score represents better functioning.	from baseline to Week 52, baseline to Week 104, and Week 16 to Week 52
Percentage of Participants Maintaining Vision (<3 Lines Loss) at Week 52 Compared With Baseline	Participants maintained 3 lines (15 letters) vision loss in BCVA (Best-corrected visual acuity) as measured by the ETDRS (Early Treatment Diabetic Retinopathy Study) letter.	At week 52
Percentage of Participants Gained 3-line at Week 52 and Week 104 Compared With Baseline	Participants gained 3 lines (15 letters) in BCVA (Best-corrected visual acuity) as measured by the ETDRS (Early Treatment Diabetic Retinopathy Study) letter.	At Week 52 and Week 104
Change in Central Retinal Thickness (CRT)	CRT were evaluated using spectral domain Optical coherence tomograph (OCT).	From baseline to Week 52, baseline to Week 104, Week 16 to Week 52, and Week 16 to Week 104
Number of Study Drug Injections From Baseline to Week 52 and Baseline to Week 104		At Week 52 and Week 104
Duration of Last Treatment Interval		Early-Start T&E: from week 16 up to Week 104 or early termination; Late-Start T&E: From end of Year 1 up to Week 104 or early termination
Percentage of Participants Requiring Retreatment at 8 Weeks, 10 Weeks, 12 Weeks, 14 Weeks, and 16 Weeks as the Last Treatment Interval		at 8 weeks, 10 weeks, 12 weeks, 14 weeks, and 16 weeks

Collaborators and Investigators

• Sponsor: Bayer
• Collaborators: Regeneron Pharmaceuticals
• Investigators: Study Director: Bayer Study Director, Bayer

Publications and helpful links

General Publications

• Mitchell P, Holz FG, Hykin P, Midena E, Souied E, Allmeier H, Lambrou G, Schmelter T, Wolf S; ARIES study investigators. EFFICACY AND SAFETY OF INTRAVITREAL AFLIBERCEPT USING A TREAT-AND-EXTEND REGIMEN FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: The ARIES Study: A Randomized Clinical Trial. Retina. 2021 Sep 1;41(9):1911-1920. doi: 10.1097/IAE.0000000000003128. Erratum In: Retina. 2022 Sep 1;42(9):e43.
• Wolf S, Holz FG, Midena E, Souied EH, Lambrou G, Machewitz T, Allmeier H, Mitchell P; ARIES Study Investigators. Patients with Neovascular Age-Related Macular Degeneration Requiring Intensive Intravitreal Aflibercept Treatment: An ARIES Post Hoc Analysis. Ophthalmol Ther. 2022 Oct;11(5):1793-1803. doi: 10.1007/s40123-022-00541-8. Epub 2022 Jul 12.
• Chaudhary V, Holz FG, Wolf S, Midena E, Souied EH, Allmeier H, Lambrou G, Machewitz T, Mitchell P; ARIES study investigators. Association Between Visual Acuity and Fluid Compartments with Treat-and-Extend Intravitreal Aflibercept in Neovascular Age-Related Macular Degeneration: An ARIES Post Hoc Analysis. Ophthalmol Ther. 2022 Jun;11(3):1119-1130. doi: 10.1007/s40123-022-00491-1. Epub 2022 Mar 18.
• Tuerksever C, Somfai GM, Oesch S, Machewitz T, Hasler PW, Zweifel S. Hypothetical Switch of Anti-Vascular Endothelial Growth Factor in Neovascular Age-Related Macular Degeneration: An ARIES Post Hoc Analysis. Ophthalmol Ther. 2022 Apr;11(2):613-627. doi: 10.1007/s40123-021-00448-w. Epub 2022 Jan 23.

Helpful Links

• Click here to find further information and, after study completion, the study results according to Bayer's transparency standards

Study record dates

Study Major Dates

• Study Start (Actual): November 19, 2015
• Primary Completion (Actual): April 26, 2019
• Study Completion (Actual): April 26, 2019

Study Registration Dates

• First Submitted: October 20, 2015
• First Submitted That Met QC Criteria: October 20, 2015
• First Posted (Estimated): October 21, 2015

Study Record Updates

• Last Update Posted (Actual): November 8, 2023
• Last Update Submitted That Met QC Criteria: November 3, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Neovascular age-related macular degeneration; nAMD)
• 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; Aflibercept
• Other Study ID Numbers: 17508; 2014-003132-39 (EudraCT Number)

Drug and device information, study documents

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