Real Life of Aflibercept in France in Patients Refractory to Ranibizumab: Observational Study in Wet AMD (TITAN)

A retrospecTive and Prospective Non-Interventional Study to Assess the Clinical pracTice in Real Life for Patients With Wet AMD Refractory to raNibizumab and Switching to Aflibercept

The aim of the TITAN study is to describe the clinical practices of a cohort of patients with wAMD refractory to ranibizumab (persistence of intra-retinal and/or subretinal fluid) who switch to aflibercept after less than 12 months of ranibizumab treatment.

The study will be conducted in real-life conditions and will allow describing conditions of use of aflibercept in patients refractory to ranibizumab

Study Overview

• Status: Completed
• Conditions: Wet Macular Degeneration
• Intervention / Treatment: Drug: Aflibercept (EYLEA, BAY-86-5321)

Detailed Description

The study is both retrsopective and prospective to collect local real life data on patients under routine treatment.

The observation periods starts on January 2014. Patients who initiated a treatment by Aflibercept between the 1st of january 2014 and the 31 December 2015 will be enrolled.

• Study Type: Observational
• Enrollment (Actual): 236

Contacts and Locations

Study Locations

• France
  • Multiple Locations, France

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with a diagnosis of wAMD refractory to ranibizumab (persistence of fluid) who started a treatment with Anti VEGF (Aflibercept) may be included in the study

Description

Inclusion Criteria:

• Man or woman > 18 years old
• Patient with wAMD previously treated with ranibizumab (for less than 12 months before initiation of Aflibercept)
• Refractory to ranibizumab (defined by persistent fluid despite a treatment conducted according to the HAS French recommendations with at least 3 loading doses injections)
• Patient who switched to aflibercept (Eylea) between 1st of January 2014 and 30th June 2015
• Written informed consent given

Exclusion Criteria:

• Patient who do not meet the local indication criteria for aflibercept treatment. Contraindications listed in the local SmPC (Summary of Product Characteristics) have to be considered
• Recurrent patients with wAMD previously treated with ranibizumab and switched to aflibercept because of a high recurrence rate (recurrent patients described by Yonegawa et al.in AJO (American Journal of Ophthalmology )2013= exudation suppressed but high rate of injections)
• Patient who have been previously treated by any macular laser Visudyne/PD (Photodynamic therapy)
• Patient with a Visual Acuity (VA) <1/10
• Patient with Fibrosis involving Macula
• Patient with atrophic AMD
• Patient with any other retinal disease as myopia, diabetic retinopathy, diabetic macular oedema,chorioretinal anastomosis (CRA),, angioid streaks
• Patients taking part in an interventional study at the time of enrolment

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Group 1; According to the recommendations of the Summary of Products Characteristics (SmPC) Administration by intravitreal injection	Drug: Aflibercept (EYLEA, BAY-86-5321); st year: 3 monthly injections followed by 1 injection every two months; nd year and following: injection according the visual and anatomical results observed the 1st year

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment success rate (defined as a gain of at least 1 letter in BCVA and/or a diminution of CRT (expressed in µm))	The 12 month follow up visit is the visit 12 month after the first injection of aflibercept	Between initial visit and 12 month follow up visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients whose BCVA increases by ≥ 0 letter, ≥ 5 letters, ≥ 10 letters, ≥15 letters	The end of study visit is the visit 12 month after the first injection of aflibercept or after last follow up visit when the patient drop out the study whichever apply..	Between initial visit and up to 1 year maximum
Proportion of patients with less than 15 letters loss		Between initial visit and up to 1 year maximum
Proportion of patients with dry-OCT		Between initial visit and up to 1 year maximum
Mean duration of treatment with ranibizumab before initiation of aflibercept		Between initial visit and up to 1 year maximum
Mean change in Central retinal thickness in µm (OCT)		Between initial visit and up to 1 year maximum

Collaborators and Investigators

• Sponsor: Bayer
• Collaborators: Regeneron Pharmaceuticals

Publications and helpful links

General Publications

• Razavi S, Kodjikian L, Giocanti-Auregan A, Dufour I, Souied E. Efficacy and safety of intravitreal aflibercept in ranibizumab-refractory patients with neovascular age-related macular degeneration. BMC Ophthalmol. 2021 Feb 17;21(1):90. doi: 10.1186/s12886-021-01841-6.

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 1, 2016
• Primary Completion (ACTUAL): January 18, 2017
• Study Completion (ACTUAL): August 18, 2017

Study Registration Dates

• First Submitted: December 17, 2014
• First Submitted That Met QC Criteria: December 19, 2014
• First Posted (ESTIMATE): December 22, 2014

Study Record Updates

• Last Update Posted (ACTUAL): July 2, 2018
• Last Update Submitted That Met QC Criteria: June 29, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Keywords: Aflibercept; Real life; Switch; Wet-AMD; Refractory patients to ranibizumab
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Wet Macular Degeneration; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Aflibercept
• Other Study ID Numbers: 17405; EY1413FR (OTHER: company internal)