Maximum Treatment Interval With Aflibercept T&E

Investigation of the Maximal Treatment Interval and Long-term Remission and the Associated Factors of Neovascular AMD Treated With Anti-VEGF Using Treat and Extend Strategy

To evaluate the duration of effectiveness of anti-VEGF (Aflibercept) by analyzing the percentage of patients whose maximum treatment interval is extended to 16 weeks and beyond in 24 months and their long-term remission.

Study Overview

• Status: Recruiting
• Conditions: Neovascular Age-related Macular Degeneration
• Intervention / Treatment: Drug: Aflibercept Injection [Eylea]

Detailed Description

This is an Observational, prospective, single arm study. The distribution of maximum treatment interval extended within 2 year among nAMD patients with Aflibercept Treat-and-Extend(T&E) regimen will be analyzed. And Clinical indicators for fast extension of treatment interval and emering disease activity will be captured.

To maximize Vision acuity (VA) outcome and reduce treatment burden of neovascular age-related macular degeneration (nAMD) patients, the T&E regimen has become popular in recent years. Sufficient drug durability is the key element to support T&E regimen. Clinical trials with aflibercept suggest a longer duration of VEGF suppression than with bevacizumab or ranibizumab, which is also supported by pharmacokinetic models, and mean duration of vitreous VEGF suppression by aflibercept injection was demonstrated as > 71 ± 18 days. With these attributes, while managed by intravitreal injection aflibercept (IVI-ALF) T&E regimen, it has been shown in ALTAIR study that around 40% and 60% of patients had treatment interval extended to 12 week and 16 weeks at week 96 respectively.

Nevertheless, it was observed that the distribution of treatment interval is polarized, a group of patients would eventually reach a stable disease status with only few treatments needed per year, while another group of patients may still need more intensive treatment even shorter than 8 week interval. To maximize benefit of patients with practical and personalized IVT-AFL T&E regimens, it is important to provided further evidence to support maximizing treatment interval as well as clinical indicators to take precise action to active disease. Therefore, this study is designed to understand the potential durability of Aflibercept by analyzing maximum treatment interval with IVT-AFL in 2 years, and explore clinical indicators to guide optimal T&E regimen for each patient.

Patients are treated with Aflibercept 2.0 mg following the T&E criteria in Taiwan local consensus (listed as below). Once the treatment interval is extended to 16 weeks, and the patient has two consecutive 16-week treatment interval, treatment strategy will be changed to pro re nata (PRN) with monthly follow-up. IVI-AFL will immediately be applied once there is any disease activity detected.

During the study, patients will be monitored with BCVA, fundus photograph, structural OCT, OCT Angiography.

T&E criteria in Taiwan local consensus:

• Extension: No BCVA loss ≥ 5 ETDRS letters (or 1 line of Snellen chart) AND dry retina§,†, #
• Maintain: No BCVA loss ≥ 5 ETDRS letters (or 1 line of Snellen chart) AND non-increased fluid§
• Shortening: Any increased fluid with BCVA loss ≥ 5 ETDRS letters (or 1 line of Snellen chart)‡, # OR new macular hemorrhage OR new neovascularization

"§"Absence of macular hemorrhage and neovascularization is required.

"†"Non-increased fluid after 3 more consecutive monthly injections following initial treatment could be considered as persistent fluid, and the injection interval could be extended if VA is stable.

"‡" Either increased fluid or BCVA loss ≥ 5 ETDRS letters alone could be maintained at current treatment interval.

"#" Extension or shortening can be by 2 or 4 weeks

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

• Study Contact: Name: Cheng-Kuo Cheng, MD; Phone Number: 2074 886-2833-2211; Email: ckcheng.md@gmail.com

Study Locations

• Taiwan
  • Taipei, Taiwan
    • Recruiting
    • Shin Kong Memorial Wu Ho-Su Hospital
    • Contact: Sam Lin, MD; Phone Number: 2074 886-2-2833-2211; Email: samlin.skhctc@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Treatment-naïve nAMD and PCV patients

Description

Inclusion Criteria:

• -Treatment-naïve patients with subfoveal CNV secondary to wet AMD and PCV, with visual impairment being exclusively due to an symptomatic neovascular AMD.
• - -Clinical status meet the national reimbursement criteria

Exclusion Criteria:

• - Any contraindications as listed in the local intravitreal aflibercept package insert
• - Any active periocular or ocular infection or inflammation at baseline
• - Uncontrolled glaucoma (intraocular pressure [IOP] ≥30 mm Hg on medication) at baseline
• - Neovascularisation of the iris or neovascular glaucoma at baseline
• - Visually significant cataract, severe vitreous haemorrhage, rhegmatogenous retinal detachment, proliferative diabetic retinopathy or CNV of any cause other than wet AMD at baseline
• - Structural damage to the center of the macula in either eye that is likely to preclude improvement in VA following the resolution of macular edema or any other condition expected to permanently limit VA outcomes over the course of the study

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The percentage of patients whose maximum treatment interval is extended to 24 months	2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Find the prediction factors associated with extension to 16 weeks and beyond by univariate and multivariate analysis	2 years
Find the prediction factors associated with occurrence of disease activity by univariate and multivariate analysis	2 years
The percentage of patients whose maximum treatment interval is extended to 16 weeks and beyond in 24 months in PCV and wAMD subgroup	2 years
Mean change in BCVA from baseline to month 24	2 years
Mean change in central subfield thickness from baseline to month 24	2 years
Proportion of patients who gain ≧15 ETDRS letters from baseline to month 24	2 years
Mean number of injections in each group from baseline to month 24	2 years
Mean treatment interval from baseline to month 24	2 years

Collaborators and Investigators

• Sponsor: Shin Kong Wu Ho-Su Memorial Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 1, 2022
• Primary Completion (ANTICIPATED): August 1, 2024
• Study Completion (ANTICIPATED): April 1, 2025

Study Registration Dates

• First Submitted: April 5, 2022
• First Submitted That Met QC Criteria: April 19, 2022
• First Posted (ACTUAL): April 25, 2022

Study Record Updates

• Last Update Posted (ACTUAL): April 25, 2022
• Last Update Submitted That Met QC Criteria: April 19, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Aflibercept
• Other Study ID Numbers: 20211006R

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No