A Study to Learn How Well Aflibercept Injected Into the Eye Works and How Safe it is When Given in Customized Treatment Intervals in Patients With an Eye Disease Called Neovascular Age-related Macular Degeneration After Start of Treatment (XPAND)

A Parallel-group Phase 4, Open-label, Two-arm Study to Assess the Safety and Efficacy of Intravitreal (IVT) Aflibercept With Proactive Customized Treatment Intervals in Patients ≥50 Years of Age With No Fluid Due to Choroidal Neovascularization (CNV) Lesions Secondary to Neovascular (Wet) Age-related Macular Degeneration (nAMD) Following Treatment Initiation With Aflibercept

Researchers are looking for a better way to treat people who have neovascular (wet) age-related macular degeneration (nAMD or wet AMD). In people with wet AMD, the body makes too much of a protein called vascular endothelial growth factor (VEGF). This causes too many blood vessels to grow in the area of sharpest vision in the eye, called macula. Fluid buildup due to leakage from these vessels can damage the macula, leading to vision problems such as blurring or a blind spot in the central (straight ahead) vision needed for reading or face recognition or car driving. Wet AMD is common in people aged 50 and older.

The study treatment intravitreal aflibercept (also called BAY865321) is injected into the eye. It works by blocking the VEGF protein and thus reduces blood vessel growth. It has already been approved for patients with wet AMD to be given as intravitreal injection monthly at start and then every 8 weeks or longer. Repeated injections of aflibercept prevent worsening of vision but place a burden on the patient.

Doctors try to increase the time between injections (treatment interval) in routine clinical practice based on individual patient needs. This is called treat and extend (T&E). Treatment intervals are stepwise extended or shortened depending on how the treatment works. This is checked with optical coherence tomography (OCT), an imaging technique used to observe relevant changes in the eye.

The main purpose of this study is to learn how well aflibercept works if treatment intervals are extended faster (timepoint of extension is the same for both treatments arms), compared to standard T&E regimen in people with wet AMD in a preselected patient population with no fluid after treatment initiation.

To answer this, researchers will assess changes in vision called best corrected visual acuity (BCVA) between study start and after 36 weeks. Changes will then be compared between participants whose treatment intervals were extended early and those on standard T&E regimen.

All participants will receive 2 mg aflibercept as intravitreal injection for up to 52 weeks in intervals of every 4 to 16 weeks.

Each participant will be in the study for up to 56 weeks. During this time 4 visits to the study site are set for all participants. The other visits are set individually. A final phone call is planned 3 days after treatment at the end of study.

During the study, the doctors and their study team will:

• check patients' eye health using various eye examination techniques (slit lamp microscopy, OCT, and ophthalmoscopy) that may necessitate eye drops to widen the pupil)
• measure patients' eye vision (BCVA)
• do physical examinations
• check vital signs
• ask the participants questions about how they are feeling and what adverse events they are having.

An adverse event is any medical problem that a participant has during a study. Doctors keep track of all adverse events that happen in studies, even if they do not think the adverse events might be related to the study treatments.

In addition, participants in the fast extension arm will be provided with a home monitoring OCT device.

Study Overview

• Status: Terminated
• Conditions: Neovascular (Wet) Age-related Macular Degeneration
• Intervention / Treatment: Drug: Aflibercept(BAY86-5321, Eylea)

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Bayer Clinical Trials Contact; Phone Number: (+)1-888-84 22937; Email: clinical-trials-contact@bayer.com

Study Locations

• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K2B7E9
      • Retina Center of Ottawa
  • Quebec
    • Sherbrooke, Quebec, Canada, J1J 2B8
      • GOGiunta ophtalmologie
• United Kingdom
  • Bristol, United Kingdom, BS12LX
    • Bristol Eye Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Written informed consent and 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 informed consent form (ICF).
• Men and women ≥50 years of age.
• At treatment initiation, active macular neovascular lesions secondary to nAMD (Patients with polypoidal choroidal vasculopathy or retinal angiomatous proliferation are eligible to participate in the study, and their condition should be captured in the electronic case report form [eCRF]).
• Treatment initiation with 3 × monthly IVT aflibercept injections (Weeks -16, -12, and -8 to planned study baseline visit) resulting in absence of any fluid at week -8.
• ETDRS BCVA of at least 25 letters (20/320 Snellen equivalent) in the study eye at screening visit.
• Willing, committed, and able to return for all clinic visits and complete all study-related procedures.
• Able to use the provided monitoring device and willing to perform 5 × weekly self-assessments in the Investigator's opinion.
• 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.

Exclusion Criteria:

• Any contraindication to IVT anti-vascular endothelial growth factor (VEGF) treatment or treatment with Eylea® as detailed in the Summary of Product Characteristics (SmPC).
• Any prior ocular (in the study eye) or systemic treatment (including investigational agents) or surgery for nAMD, except the 3 × monthly IVT aflibercept injections required for treatment initiation and dietary supplements or vitamins.
• Any presence of intraretinal and subretinal fluid.

• Any ocular or systemic condition expected to interfere with study outcomes and procedures, including but not limited to:

  • Scar, fibrosis or other lesions (e.g., retinal pigment epithelium [RPE] tears, macular hole stage 2 or above and others) involving the center of the macula in the study eye.
  • Clinically relevant opacities or conditions involving the optic media including cataract, corneal dystrophies or s.p. corneal transplant in the study eye.
  • Uncontrolled glaucoma (defined as IOP ≥25 mm Hg despite treatment with antiglaucoma medication) in the study eye or prior trabeculectomy or other filtration surgery in the study eye.
  • Intraocular surgery, periocular surgery, or cataract surgery within 90 days before Day 1 in the study eye, except the IVT aflibercept injections required for treatment initiation and any history of vitrectomy, retinal radiation therapy, retinal detachment or treatment or surgery for retinal detachment in the study eye.
  • Aphakia or pseudophakia with absence of posterior capsule (unless as a result of an yttrium aluminum garnet posterior capsulotomy) in the study eye.
• Participation as a patient in any clinical study within 12 weeks before screening.
• Close affiliation with the investigational site; e.g., a close relative of the Investigator, dependent person (e.g., employee or student of the investigational site).
• Previously screen failed patients for this study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Customized treatment interval; After the initial study injection at baseline, participants will receive their next study injection at Week 16. Participants in this study arm will also be issued a home monitoring device, which will allow for regular OCT monitoring (at least 5 times a week) at home.	Drug: Aflibercept(BAY86-5321, Eylea); 2mg, intravitreal (IVT) injection
Active Comparator: Treat and extend (T&E) 2 week adjustment; Participants will receive treatment in intervals maintained (8 weeks) or adjusted in 2 weeks increments each time (up to a maximum of 16 weeks and minimum of 4 weeks), as long as all extension/shortening criteria are met.	Drug: Aflibercept(BAY86-5321, Eylea); 2mg, intravitreal (IVT) injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in best-corrected visual acuity (BCVA)	BCVA is measured by the early treatment diabetic retinopathy study (ETDRS) letter score for the study eye	From baseline to Week 36

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of IVT aflibercept injections per patient		From baseline up to Week 52
Number of IVT aflibercept injections per patient		From baseline up to Week 36
Number of patients achieving pre-defined treatment intervals (≥4, ≥8, ≥10, ≥12¸ ≥14, and 16 weeks)		At Week 36 and Week 52
Change in best-corrected visual acuity (BCVA)	BCVA is measured by the early treatment diabetic retinopathy study (ETDRS) letter score for the study eye	From baseline up to Week 52
Number of participants with treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs)		From baseline up to Week 36 and Week 52

Collaborators and Investigators

• Sponsor: Bayer
• Collaborators: Regeneron Pharmaceuticals

Publications and helpful links

Helpful Links

• Click here to find information for studies related to Bayer products. To find this study enter the ClinicalTrials.gov identifier (NCT) number or Bayer Study Identifier (ID) in the search field.

Study record dates

Study Major Dates

• Study Start (Actual): April 25, 2023
• Primary Completion (Actual): July 11, 2023
• Study Completion (Actual): July 11, 2023

Study Registration Dates

• First Submitted: July 22, 2022
• First Submitted That Met QC Criteria: July 22, 2022
• First Posted (Actual): July 26, 2022

Study Record Updates

• Last Update Posted (Actual): September 1, 2023
• Last Update Submitted That Met QC Criteria: August 30, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Aflibercept; Anti-vascular endothelial growth factor; Treatment interval extension
• 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: 21912; 2022-000690-73 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access.

As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014.

Interested researchers can use www.clinicalstudydatarequest.com to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the Study sponsors section of the portal.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes