Japanese Treat and Extend Study of Aflibercept in Neovascular Age-related Macular Degeneration

Study Overview
=================
Brief Summary
-----------------
To assess the efficacy of intravitreal (IVT) administration of aflibercept with two different approaches of Treat and Extend dosing regimens in Japanese subjects with neovascular (wet) Age-related Macular Degeneration (wAMD) . To assess the safety of IVT administration of aflibercept with two different approaches of Treat and Extend dosing regimen in Japanese subjects with wAMD for up to 2 years.

Official Title
-----------------
A Randomized, Open-label Phase 4 Study Evaluating the Efficacy and Safety of Repeated Doses of Intravitreal Aflibercept With Variable Treatment Intervals in Japanese Subjects With Neovascular Age-related Macular Degeneration

Conditions
-----------------
Wet Macular Degeneration

Intervention / Treatment
-----------------
* Drug: Aflibercept (Eylea, VEGF Trap-Eye, BAY86-5321)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Japanese men and women ≥ 50 years of age Active primary subfoveal choroidal neovascularization (CNV) lesions secondary to wAMD, including juxta-foveal lesions that affect the fovea as evidenced by fluorescein angiography (FA) in the study eye Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) of 73 to 25 letters (approximately 20/40 to 20/320 at Snellen equivalent) in the study eye Exclusion Criteria: Prior treatment of the study eye with intraocular anti-VEGF(Vascular Endothelial Growth Factor) agents, verteporfin photodynamic therapy (PDT), other laser, intraocular corticosteroids, surgical interventions (except cataract surgery more than 30 days prior to screening) or systemic use of anti-VEGF products within 3 months prior to study entry Active or suspected infection in or surrounding of the study eye Active severe intraocular inflammation in the study eye Intraocular pressure (IOP) ≥ 25 mmHg in the study eye Ocular condition in the study eye which may impact vision and confound study outcomes

Ages Eligible for Study
-----------------
Minimum Age: 50 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 2 Weeks adjustment<br>Participants received Aflibercept IVT injection at Week 0, Week 4, Week 8 and Week 16 followed by the variable treatment intervals with the criteria of Treat and Extend regimen. In the case the study eye of a participant met the criteria, the length of treatment interval was to be extended or shortened by 2 weeks from the last interval, respectively. Minimum/Maximum treatment interval is 8 weeks and 16 weeks during Week 16 to 96. | Drug: Aflibercept (Eylea, VEGF Trap-Eye, BAY86-5321)<br>* Aflibercept 2mg is intravitreally injected.<br>|
| Experimental: 4 Weeks adjustment<br>Participants received Aflibercept IVT injection at Week 0, Week 4, Week 8 and Week 16 followed by the variable treatment intervals. In the case the study eye of a participant met the criteria of the shortening, the length of the treatment interval was to be shortened by 2 weeks. But when the last treatment interval for a participant was extended by 4 weeks from the second last interval, the treatment interval was shortened by 4 weeks. In the case the study eye of a participant met the criteria of the extension, the length of the treatment interval was to be extended by 4 weeks. But when a participant had a history of receiving treatment with interval shortened by 4 weeks during this study, the length of the extension was 2 weeks. Minimum/Maximum treatment interval is 8 weeks and 16 weeks during Week 16 to 96. | Drug: Aflibercept (Eylea, VEGF Trap-Eye, BAY86-5321)<br>* Aflibercept 2mg is intravitreally injected.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in BCVA at Week 52 | Visual functions of the study eye (at every visit) and the fellow eye were assessed, according to the ETDRS protocol as described in detail in the operation manual. A higher score represents better functioning. | Baseline and Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Maintained Vision at Week 52 | A participant was classified as maintaining vision if the participant had lost fewer than 15 letters in the ETDRS letter score compared to baseline. | Week 52 | 
| Percentage of Participants Who Gained at Least 15 Letters of Vision Compared to Baseline at Week 52 |  | Baseline and Week 52 | 
| Mean Change in Central Retinal Thickness (CRT) From Baseline at Week 52 |  | Baseline and week 52 | 
| Percentage of Participants Without Fluid on Optical Coherence Tomography (OCT) at Week 52 | A participant was classified as without fluid if Evidence of new or persistent fluid on OCT was No. | Week 52 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Eylea,, Aflibercept, Treat and Extend regimen, Age-related macular degeneration