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)

• ClinicalTrials.gov Identifier: NCT02581891
• Recruitment Status: Completed
• First Posted: October 21, 2015
• Results First Posted: May 21, 2020
• Last Update Posted: May 21, 2020
• Sponsor: Bayer
• Collaborator: Regeneron Pharmaceuticals
• Information provided by (Responsible Party): Bayer

Tracking Information

• First Submitted Date: October 20, 2015
• First Posted Date: October 21, 2015
• Results First Submitted Date: April 21, 2020
• Results First Posted Date: May 21, 2020
• Last Update Posted Date: May 21, 2020
• Actual Study Start Date: November 19, 2015
• Actual Primary Completion Date: April 26, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 12, 2020)

Change in BCVA as Measured by the ETDRS Letter Score [ Time Frame: From Week 16 to Week 104 ]

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.

• Original Primary Outcome Measures (submitted: October 20, 2015): Change in best corrected visual acuity (BCVA) as measured by the Early Treatment Diabetic Retinopathy Study (ETDRS) letter score [ Time Frame: Week 104 ]

Current Secondary Outcome Measures (submitted: May 12, 2020)

• Percentage of Participants Maintaining Vision (<3 Lines Loss) at Week 104 Compared With Baseline [ Time Frame: at Week 104 ]
  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 [ Time Frame: 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.
• Percentage of Participants Maintaining Vision (<3 Lines Loss) at Week 52 Compared With Baseline [ Time Frame: At week 52 ]
  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 [ Time Frame: At Week 52 and Week 104 ]
  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) [ Time Frame: From baseline to Week 52, baseline to Week 104, Week 16 to Week 52, and Week 16 to Week 104 ]
  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 [ Time Frame: At Week 52 and Week 104 ]
• 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 ]
• 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 ]

Original Secondary Outcome Measures (submitted: October 20, 2015)

• Proportion of subjects maintaining vision (<3 lines loss) [ Time Frame: Weeks 52 and 104 ]
• Change in BCVA as measured by the ETDRS letter score [ Time Frame: Weeks 52 and 104 ]
• Change in Central Retinal Thickness (CRT) [ Time Frame: Weeks 52 and 104 ]
• Number of study drug injections [ Time Frame: Weeks 52 and 104 ]
• Duration of last re-treatment interval [ Time Frame: Week 104 ]
• Proportion of subjects requiring retreatment at 8, 10, 12, 14, and 16 weeks as the last treatment interval [ Time Frame: Week 104 ]
• Proportion of 3-line vision gainers [ Time Frame: Weeks 52 and 104 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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)
• 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.

• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Macular Degeneration

Intervention

• 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

Study Arms

• Experimental: Early-start T&E / Arm 1
  Early-start T&E arm: test group, early treatment individualization
  Intervention: Drug: Eylea (Intravitreal Aflibercept, VEGF Trap-Eye, BAY86-5321)
• Active Comparator: Late-start T&E / Arm 2
  Late-start T&E arm; per label, control group, treatment individualization after Year 1
  Intervention: Drug: Eylea (Intravitreal Aflibercept, VEGF Trap-Eye, BAY86-5321)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 29, 2018): 287
• Original Estimated Enrollment (submitted: October 20, 2015): 268
• Actual Study Completion Date: April 26, 2019
• Actual Primary Completion Date: April 26, 2019 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 50 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Canada, France, Germany, Hungary, Italy, Spain, United Kingdom
• Removed Location Countries: Netherlands

Administrative Information

• NCT Number: NCT02581891
• Other Study ID Numbers: 17508; 2014-003132-39 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• 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

• IPD Sharing Statement: Not Provided
• Responsible Party: Bayer
• Study Sponsor: Bayer
• Collaborators: Regeneron Pharmaceuticals

Investigators

• Study Director: Bayer Study Director; Bayer

• PRS Account: Bayer
• Verification Date: May 2020