Clinical trial NCT02581891: 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
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Macular Degeneration
Keywords: Neovascular age-related macular degeneration
nAMD)
Lead sponsor: Bayer
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2015-10-21
Enrollment: 287
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in BCVA as Measured by the ETDRS Letter Score
timeFrame: From Week 16 to Week 104
Secondary outcomes:
measure: Percentage of Participants Maintaining Vision (<3 Lines Loss) at Week 104 Compared With Baseline
timeFrame: at Week 104
measure: Change in BCVA From Baseline to Week 52, Baseline to Week 104, and Week 16 to Week 52
timeFrame: from baseline to Week 52, baseline to Week 104, and Week 16 to Week 52
measure: Percentage of Participants Maintaining Vision (<3 Lines Loss) at Week 52 Compared With Baseline
timeFrame: At week 52
measure: Percentage of Participants Gained 3-line at Week 52 and Week 104 Compared With Baseline
timeFrame: At Week 52 and Week 104
measure: Change in Central Retinal Thickness (CRT)
timeFrame: From baseline to Week 52, baseline to Week 104, Week 16 to Week 52, and Week 16 to Week 104
measure: Number of Study Drug Injections From Baseline to Week 52 and Baseline to Week 104
timeFrame: At Week 52 and Week 104
measure: Duration of Last Treatment Interval
timeFrame: 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
measure: Percentage of Participants Requiring Retreatment at 8 Weeks, 10 Weeks, 12 Weeks, 14 Weeks, and 16 Weeks as the Last Treatment Interval
timeFrame: at 8 weeks, 10 weeks, 12 weeks, 14 weeks, and 16 weeks
Other outcomes:
Locations:
city: Strathfield
country: Australia
state: New South Wales
city: Sydney
country: Australia
state: New South Wales
city: Westmead
country: Australia
state: New South Wales
city: East Melbourne
country: Australia
state: Victoria
city: Launceston
country: Australia
city: Hamilton
country: Canada
state: Ontario
city: Ottawa
country: Canada
state: Ontario
city: Boisbriand
country: Canada
state: Quebec
city: Creteil Cedex
country: France
city: Nice cedex 1
country: France
city: Freiburg
country: Germany
state: Baden-Württemberg
city: Tübingen
country: Germany
state: Baden-Württemberg
city: Hannover
country: Germany
state: Niedersachsen
city: Bonn
country: Germany
state: Nordrhein-Westfalen
city: Köln
country: Germany
state: Nordrhein-Westfalen
city: Sulzbach
country: Germany
state: Saarland
city: Chemnitz
country: Germany
state: Sachsen
city: Berlin
country: Germany
city: Budapest
country: Hungary
city: Budapest
country: Hungary
city: Budapest
country: Hungary
city: Budapest
country: Hungary
city: Budapest
country: Hungary
city: Budapest
country: Hungary
city: Debrecen
country: Hungary
city: Pecs
country: Hungary
city: Szombathely
country: Hungary
city: Roma
country: Italy
state: Lazio
city: Milano
country: Italy
state: Lombardia
city: Milano
country: Italy
state: Lombardia
city: Padova
country: Italy
state: Veneto
city: Oviedo
country: Spain
state: Asturias
city: Madrid
country: Spain
city: Zaragoza
country: Spain
city: Canterbury
country: United Kingdom
state: Kent
city: Bristol
country: United Kingdom
city: Liverpool
country: United Kingdom
city: London
country: United Kingdom
city: Oxford
country: United Kingdom
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.