Managing neovascular age-related macular degeneration over 2 years using of different schedules of 2 mg aflibercept injected in the eye (ARIES)

Phase 1

Conditions: eovascular age-related macular degeneration (nAMD)
MedDRA version: 20.0Level: PTClassification code 10071129Term: Neovascular age-related macular degenerationSystem Organ Class: 10015919 - Eye disorders
Therapeutic area: Diseases [C] - Eye Diseases [C11]

Registration Number: EUCTR2014-003132-39-IT

Lead Sponsor: BAYER AG

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 287

Inclusion Criteria

1.Written informed consent.
2.Men and women = 50 years of age.
3.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.
4.ETDRS BCVA of 73 to 25 letters (20/40 to 20/320 Snellen equivalents) in the study eye.
5.Willing, committed, and able to return for all clinic visits and complete all study-related procedures.
6.Able to read, (or, if unable to read due to visual impairment, be read to verbatim by the person administering the informed consent or a family member) understand and willing to sign the ICF.
7.The area of CNV must occupy at least 50% of the total lesion.
8.Women and men of reproductive potential must agree to use adequate contraception when sexually active. This applies for the time period between signing of the ICF and 3 months after the last administration of study drug. The definition of adequate contraception will be based on the judgment of the investigator and on local requirements. Acceptable methods of contraception include, but are not limited to, (i) condoms (male or female) with or without a spermicidal agent; (ii) diaphragm or cervical cap with spermicide; (iii) intra-uterine device; (iv) hormone-based contraception. Subjects must agree to utilize two reliable and acceptable methods of contraception simultaneously.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 41
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 227

Exclusion Criteria

1.Any prior ocular (in the study eye) or systemic treatment or surgery for nAMD, except dietary supplements or vitamins.
2.Any prior or concomitant therapy with another investigational agent to treat nAMD in the study eye.
3.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.
4.Total lesion size >12 disc areas (30.5 mm2, including blood, scars and neovascularization) as assessed by FA in the study eye.
5.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).
6.Scar or fibrosis making up >50% of the total lesion in the study eye.
7.Scar, fibrosis, or atrophy involving the center of the fovea in the study eye.
8.Presence of retinal pigment epithelial tears or rips involving the macula in the study eye.
9.History of any vitreous hemorrhage within 4 weeks before screening in the study eye.
10.Presence of other causes of CNV in the study eye.
11.Prior vitrectomy in the study eye.
12.History of retinal detachment or treatment or surgery for retinal detachment in the study eye.
13.Any history of macular hole of stage 2 and above in the study eye.
14.Any intraocular surgery, periocular surgery, or cataract surgery within 90 days before Day 1 in the study eye, except lid surgery, which may not have taken place within 1 month of screening, as long as it is unlikely to interfere with the injection.
15.Only 1 functional eye even if that eye is otherwise eligible for the study.
16.Prior trabeculectomy or other filtration surgery in the study eye.
17.Uncontrolled glaucoma (defined as IOP =25 mm Hg despite treatment with antiglaucoma medication) in the study eye.
18.Aphakia or pseudophakia with absence of posterior capsule (unless it occurred as a result of an yttrium aluminum garnet posterior capsulotomy) in the study eye.
19.Previous therapeutic radiation in the region of the study eye.
20.History of corneal transplant or corneal dystrophy in the study eye.
21.Significant media opacities, including cataract, in the study eye which might interfere with visual acuity, assessment of toxicity or FP.
22.History or clinical evidence of diabetic retinopathy, diabetic macular edema or any retinal vascular disease other than AMD in either eye.
23.Active intraocular, extraocular and periocular inflammation or infection in either eye.
24.Any ocular or periocular infection within the last 2 weeks before screening in either eye.
25.Any history of ocular or periocular Herpes simplex in either eye.
26.Any history of uveitis in either eye.
27.Presence of scleromalacia in either eye.
28.Any concurrent intraocular condition in the study eye that could require either medical or surgical intervention during the 104-week study period.
29.Any concurrent ocular conditio

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess whether 2 mg IVT aflibercept administered in an early-start T&E regimen (initiated after the first 8-weekly treatment interval) is non-inferior to 2 mg IVT aflibercept administered in a late start T&E regimen (initiated at the end of Year 1, per label) in subjects with nAMD;Secondary Objective: To assess the percentage of subjects requiring retreatment with IVT aflibercept less frequently than every 8 weeks (2Q8)<br>To assess the safety and tolerability of IVT aflibercept;Primary end point(s): Change in BCVA as measured by the ETDRS letter score from Week 16 to Week 104;Timepoint(s) of evaluation of this end point: Change from Week 16 to Week 104

Secondary Outcome Measures

Name	Time	Method

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