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

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)

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02581891

Acronym

ARIES

Enrollment

287

Registered

2015-10-21

Start date

2015-11-19

Completion date

2019-04-26

Last updated

2023-11-08

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Macular Degeneration

Keywords

Neovascular age-related macular degeneration, nAMD)

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.

Interventions

DRUGEylea (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

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

50 Years to No maximum

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.

Design outcomes

Primary

Measure	Time frame	Description
Change in BCVA as Measured by the ETDRS Letter Score	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.

Secondary

Measure	Time frame	Description
Change in BCVA From Baseline to Week 52, Baseline to Week 104, and Week 16 to Week 52	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	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	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.
Percentage of Participants Maintaining Vision (<3 Lines Loss) at Week 104 Compared With Baseline	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.
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	—
Change in Central Retinal Thickness (CRT)	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).

Countries

Australia, Canada, France, Germany, Hungary, Italy, Spain, United Kingdom

Participant flow

Recruitment details

This study was conducted from 19-Nov-2015 (First Patient First Visit) to 26-Apr-2019 (Last Patient Last Visit).

Pre-assignment details

A total of 443 participants were screened in this study. Of these, 156 participants were screening failures and did not enter the treatment period. Of the 287 treated participants, 16 were treated during the initiation phase, but were not randomized to a treatment arm after the initiation phase.

Participants by arm

Arm	Count
Early-start T&E Arm All participants during the initiation phase received Aflibercept (Eylea, BAY86-5321) 3 doses at Weeks 0, 4, and 8 followed by one dose 2Q8 (2 mg administered every 8 weeks) at Week 16. From Week 16 to Week 104 participants randomized to Early-start T&E arm (Treat and Extend arm) received treatment in individualized intervals of between 8 to16 weeks based on anatomical criteria.	135
Late-start T&E Arm All participants during the initiation phase received Aflibercept (Eylea, BAY86-5321) 3 doses at Weeks 0, 4, and 8 followed by one dose 2Q8 (2 mg administered every 8 weeks) at Week 16. From Week 16 participants randomized to Late-start T&E arm received four 2Q8 injections. In Year 2 starting at Week 48, participants received treatment in individualized intervals of between 8 to16 weeks based on anatomical criteria.	136
Total	271

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	4	6
Overall Study	Death	3	4
Overall Study	Discontinued during followup	1	0
Overall Study	Lost to Follow-up	1	2
Overall Study	Other Reasons	3	1
Overall Study	Physician Decision	0	1
Overall Study	Withdrawal by Subject	4	5

Baseline characteristics

Characteristic	Late-start T&E Arm	Early-start T&E Arm	Total
Age, Continuous	76.9 Years STANDARD_DEVIATION 8.2	76 Years STANDARD_DEVIATION 8.8	76.5 Years STANDARD_DEVIATION 8.5
Baseline BCVA letters scores (study eye)	61.3 letters STANDARD_DEVIATION 10.8	60.2 letters STANDARD_DEVIATION 12.1	60.8 letters STANDARD_DEVIATION 11.4
Baseline CRT	448.3 μm STANDARD_DEVIATION 133.1	443.7 μm STANDARD_DEVIATION 120	446.0 μm STANDARD_DEVIATION 126.4
Ethnicity (NIH/OMB) Hispanic or Latino	7 Participants	3 Participants	10 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	122 Participants	126 Participants	248 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	7 Participants	6 Participants	13 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	1 Participants	2 Participants	3 Participants
Race (NIH/OMB) Black or African American	0 Participants	1 Participants	1 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	8 Participants	1 Participants	9 Participants
Race (NIH/OMB) White	127 Participants	131 Participants	258 Participants
Sex: Female, Male Female	73 Participants	81 Participants	154 Participants
Sex: Female, Male Male	63 Participants	54 Participants	117 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	3 / 135	4 / 136	0 / 16
other Total, other adverse events	93 / 135	80 / 136	10 / 16
serious Total, serious adverse events	29 / 135	35 / 136	3 / 16

Outcome results

Primary

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.

Time frame: From Week 16 to Week 104