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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)

Primary Purpose

Macular Degeneration

Status

Completed

Phase

Phase 4

Locations

International

Study Type

Interventional

Intervention

Eylea (Intravitreal Aflibercept, VEGF Trap-Eye, BAY86-5321)

About this trial

This is an interventional treatment trial for Macular Degeneration focused on measuring Neovascular age-related macular degeneration, nAMD)

Eligibility Criteria

50 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Early-start T&E / Arm 1

Late-start T&E / Arm 2

Arm Description

Early-start T&E arm: test group, early treatment individualization

Late-start T&E arm; per label, control group, treatment individualization after Year 1

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Change in BCVA 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.

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.

Change in Central Retinal Thickness (CRT)

CRT were evaluated using spectral domain Optical coherence tomograph (OCT).

Number of Study Drug Injections From Baseline to Week 52 and Baseline to Week 104

Duration of Last Treatment Interval

Percentage of Participants Requiring Retreatment at 8 Weeks, 10 Weeks, 12 Weeks, 14 Weeks, and 16 Weeks as the Last Treatment Interval

Full Information

NCT ID

NCT02581891

First Posted

October 20, 2015

Last Updated

May 12, 2020

Sponsor

Bayer

Collaborators

Regeneron Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT02581891

Brief Title

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

Acronym

ARIES

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

2. Study Status

Record Verification Date

May 2020

Overall Recruitment Status

Completed

Study Start Date

November 19, 2015 (Actual)

Primary Completion Date

April 26, 2019 (Actual)

Study Completion Date

April 26, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Bayer

Collaborators

Regeneron Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Macular Degeneration

Keywords

Neovascular age-related macular degeneration, nAMD)

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

287 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Early-start T&E / Arm 1

Arm Type

Experimental

Arm Description

Early-start T&E arm: test group, early treatment individualization

Arm Title

Late-start T&E / Arm 2

Arm Type

Active Comparator

Arm Description

Late-start T&E arm; per label, control group, treatment individualization after Year 1

Intervention Type

Drug

Intervention Name(s)

Eylea (Intravitreal Aflibercept, VEGF Trap-Eye, BAY86-5321)

Intervention Description

3 monthly doses followed by individualized treatment intervals of between 8 to16 weeks based on protocol-defined anatomical criteria

Intervention Type

Drug

Intervention Name(s)

Eylea (Intravitreal Aflibercept, VEGF Trap-Eye, BAY86-5321)

Intervention Description

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

Primary Outcome Measure Information:

Title

Change in BCVA as Measured by the ETDRS Letter Score

Description

Time Frame

From Week 16 to Week 104

Secondary Outcome Measure Information:

Title

Percentage of Participants Maintaining Vision (<3 Lines Loss) at Week 104 Compared With Baseline

Description

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.

Time Frame

at Week 104

Title

Change in BCVA From Baseline to Week 52, Baseline to Week 104, and Week 16 to Week 52

Description

Time Frame

from baseline to Week 52, baseline to Week 104, and Week 16 to Week 52

Title

Percentage of Participants Maintaining Vision (<3 Lines Loss) at Week 52 Compared With Baseline

Description

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.

Time Frame

At week 52

Title

Percentage of Participants Gained 3-line at Week 52 and Week 104 Compared With Baseline

Description

Participants gained 3 lines (15 letters) in BCVA (Best-corrected visual acuity) as measured by the ETDRS (Early Treatment Diabetic Retinopathy Study) letter.

Time Frame

At Week 52 and Week 104

Title

Change in Central Retinal Thickness (CRT)

Description

CRT were evaluated using spectral domain Optical coherence tomograph (OCT).

Time Frame

From baseline to Week 52, baseline to Week 104, Week 16 to Week 52, and Week 16 to Week 104

Title

Number of Study Drug Injections From Baseline to Week 52 and Baseline to Week 104

Time Frame

At Week 52 and Week 104

Title

Duration of Last Treatment Interval

Time Frame

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

Title

Percentage of Participants Requiring Retreatment at 8 Weeks, 10 Weeks, 12 Weeks, 14 Weeks, and 16 Weeks as the Last Treatment Interval

Time Frame

at 8 weeks, 10 weeks, 12 weeks, 14 weeks, and 16 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

50 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Bayer Study Director

Organizational Affiliation

Bayer

Official's Role

Study Director

Facility Information:

City

Strathfield

State/Province

New South Wales

ZIP/Postal Code

2135

Country

Australia

City

Sydney

State/Province

New South Wales

ZIP/Postal Code

2000

Country

Australia

City

Westmead

State/Province

New South Wales

ZIP/Postal Code

2145

Country

Australia

City

East Melbourne

State/Province

Victoria

ZIP/Postal Code

3002

Country

Australia

City

Launceston

ZIP/Postal Code

7249

Country

Australia

City

Hamilton

State/Province

Ontario

ZIP/Postal Code

L8G 5E4

Country

Canada

City

Ottawa

State/Province

Ontario

ZIP/Postal Code

K2B 7E9

Country

Canada

City

Boisbriand

State/Province

Quebec

ZIP/Postal Code

J7H 1S6

Country

Canada

City

Creteil Cedex

ZIP/Postal Code

94010

Country

France

City

Nice cedex 1

ZIP/Postal Code

06006

Country

France

City

Freiburg

State/Province

Baden-Württemberg

ZIP/Postal Code

79106

Country

Germany

City

Tübingen

State/Province

Baden-Württemberg

ZIP/Postal Code

72076

Country

Germany

City

Hannover

State/Province

Niedersachsen

ZIP/Postal Code

30625

Country

Germany

City

Bonn

State/Province

Nordrhein-Westfalen

ZIP/Postal Code

53105

Country

Germany

City

Köln

State/Province

Nordrhein-Westfalen

ZIP/Postal Code

50924

Country

Germany

City

Sulzbach

State/Province

Saarland

ZIP/Postal Code

66280

Country

Germany

City

Chemnitz

State/Province

Sachsen

ZIP/Postal Code

09116

Country

Germany

City

Berlin

ZIP/Postal Code

10713

Country

Germany

City

Budapest

ZIP/Postal Code

1062

Country

Hungary

City

Budapest

ZIP/Postal Code

1085

Country

Hungary

City

Budapest

ZIP/Postal Code

1106

Country

Hungary

City

Budapest

ZIP/Postal Code

1115

Country

Hungary

City

Budapest

ZIP/Postal Code

1125

Country

Hungary

City

Budapest

ZIP/Postal Code

1133

Country

Hungary

City

Debrecen

ZIP/Postal Code

4032

Country

Hungary

City

Pecs

ZIP/Postal Code

7621

Country

Hungary

City

Szombathely

ZIP/Postal Code

9700

Country

Hungary

City

Roma

State/Province

Lazio

ZIP/Postal Code

00198

Country

Italy

City

Milano

State/Province

Lombardia

ZIP/Postal Code

20132

Country

Italy

City

Milano

State/Province

Lombardia

ZIP/Postal Code

20157

Country

Italy

City

Padova

State/Province

Veneto

ZIP/Postal Code

35128

Country

Italy

City

Oviedo

State/Province

Asturias

ZIP/Postal Code

33012

Country

Spain

City

Madrid

Country

Spain

City

Zaragoza

ZIP/Postal Code

50009

Country

Spain

City

Canterbury

State/Province

Kent

ZIP/Postal Code

CT1 3NG

Country

United Kingdom

City

Bristol

ZIP/Postal Code

BS1 2LX

Country

United Kingdom

City

Liverpool

ZIP/Postal Code

L7 8XP

Country

United Kingdom

City

London

ZIP/Postal Code

EC1V 2PD

Country

United Kingdom

City

Oxford

ZIP/Postal Code

OX3 9DU

Country

United Kingdom

12. IPD Sharing Statement

Citations:

PubMed Identifier

35821380

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.

Results Reference

derived

PubMed Identifier

35303285

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.

Results Reference

derived

PubMed Identifier

35066801

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.

Results Reference

derived

PubMed Identifier

33782365

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. Erratum In: Retina. 2022 Sep 1;42(9):e43.

Results Reference

derived

Learn more about this trial

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

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