Faricimab for High-frequent Aflibercept Treated Neovascular Age-related Macular Degeneration (FAN)

Faricimab for High-frequent Aflibercept Treated Neovascular Age-related Macular Degeneration: a Monocenter, Randomized, Double-masked Comparator-controlled Study (FAN)

Study purpose: To evaluate if previously high-frequent (3-5 weekly) aflibercept treated neovascular age-related macular degeneration (nAMD) can be extended in their treatment interval when switched to faricimab.

Primary objective: To assess the efficacy of faricimab compared to aflibercept in terms of durability at 32 weeks by extending treatment interval in previous high-frequent aflibercept treated nAMD.

Study Overview

• Status: Active, not recruiting
• Conditions: Neovascular Age-related Macular Degeneration
• Intervention / Treatment: Drug: Aflibercept 40 MG/ML; Drug: Faricimab 120 MG/ML

Detailed Description

There is a subgroup of nAMD patient requiring monthly interventions, when applying as needed and treat-and-extend treatment strategies. A burden for both patient/caregivers and health care systems. More durable treatment options are needed to increase the quality of life for these nAMD patients, as well as to make human resources available for the growing elderly AMD population requiring treatment.

The FAN study is a randomized, double-masked, 2-arm (comparator-controlled), phase-IV, monocenter study with a primary endpoint at 32 weeks. The study is conducted into 2 parts. Patients will receive either aflibercept or faricimab via treat-and-extend principle until the primary endpoint (part 1). As mentioned, the main objective is to assess the durability of both drugs in this particular subgroup of nAMD patients. In part 2 of the study, starting at or after 32 weeks, all patients will receive faricimab via treat-and-extend until the end of the study (56 weeks).

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Monja Michelitsch, MD; Phone Number: 0043(0)31638513817; Email: monja.michelitsch@medunigraz.at

Study Locations

• Austria
  • Styria
    • Graz, Styria, Austria, 8036
      • Department of Ophthalmolgy, Medical University Graz

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Ocular inclusion criteria:

• MNV due to AMD (nAMD)
• BVCA between and including 19 and 75 letters (Snellen equivalent approximately 20/400 to 20/32)
• ≥ 7 previous intravitreal injections with anti-VEGF
• the last ≥ 4 consecutive intravitreal injections with aflibercept
• the last aflibercept injections within the last 35 days
• interval between the last 2 aflibercept injections ≤ 35 days

Ocular exclusion criteria:

• MNV due to other causes than nAMD
• polypoidal choroidal neovascularization
• retinal pigment epithelial rip/tear
• subretinal hemorrhage of > 50% of the lesion, involving the fovea
• any macular pathology other than AMD causing structural changes of the macula and thereby affecting vision
• any active intra-/periocular infection/inflammation of the study eye
• uncontrolled glaucoma under medication (IOP >25mmHg)
• cataract surgery of the study eye within the last 3 months
• previous intraocular surgery of the study eye other than cataract surgery or intravitreal injections with anti-VEGF (e.g. vitrectomy, corneal transplant, glaucoma surgery)
• any previous laser therapy of the study eye other than Yag (yttrium aluminium garnet) laser capsulotomy (e.g. panretinal photocoagulation, verteporfin photodynamic therapy)
• refractive error of more than -6 diopters myopia
• vitreous hemorrhage
• retinal detachment

General exclusion criteria

• use of long-term systemic corticosteroids within the last 3 months
• uncontrolled blood pressure (either/both systolic blood pressure >180mmHg, diastolic blood pressure >100mmHg)
• pregnancy (pre-menopausal women MUST take a pregnancy test at time of initiation)
• breast-feeding
• myocardial infarction or stroke within the last six months
• concomitant participation in another clinical study with investigational medicinal products
• a known allergy or hypersensitivity towards eye drops needed for the examinations planned during the study, and/or the intravitreal procedure.
• a known allergy or hypersensitivity against fluorescein / indocyanine green used during angiography
• a known allergy or hypersensitivity towards any of the components of the study drug

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: group A: aflibercept first (part 1), switch to faricimab (part 2); Aflibercept 2.0mg/0.05ml intravitreal will be administered from baseline through to the first visit at or after 32 weeks in a treat-and-extend regime. At the first visit at or after 32 weeks, faricimab 6.0mg/0.05ml intravitreal will be administered in a treat-and-extend regime through to the last visit before 56 weeks.	Drug: Aflibercept 40 MG/ML; treat-and-extend; Other Names: Eylea®; Drug: Faricimab 120 MG/ML; treat-and-extend; Other Names: Vabysmo®
Experimental: group B: faricimab monotherapy; Faricimab 6.0mg/0.05ml intravitreal will be administered from baseline through to the last visit before 56 weeks in a treat-and-extend regime.	Drug: Faricimab 120 MG/ML; treat-and-extend; Other Names: Vabysmo®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of eyes with at least one extension without retinal (intra- and subretinal) fluid within the time period baseline to 32 weeks (extension success rate)	Treatment is administered at each visit. The interval between treatments is based on a treat and extend regime. The first interval between treatments, from baseline, is 4 weeks. Intra- and subretinal fluid are assessed at each visit with optical coherence tomography (OCT). Should no intra- and subretinal fluid be present on OCT, the treatment interval to the next visit is extended by 2 weeks. Is intra- and or subretinal fluid present on OCT the treatment interval to the next visit is reduced by 2 weeks. The minimum treatment interval is 4 weeks, the maximum treatment interval is 12 weeks.	at 32 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of eyes with maximum extended interval without retinal (intra- and subretinal) fluid of ≥ 6, ≥ 8, ≥ 10 weeks and (≥ 12weeks)	Treatment is administered at each visit. The interval between treatments is based on a treat and extend regime. The first interval between treatments, from baseline, is 4 weeks. Intra- and subretinal fluid are assessed at each visit with optical coherence tomography (OCT). Should no intra- and subretinal fluid be present on OCT, the treatment interval to the next visit is extended by 2 weeks. Is intra- and or subretinal fluid present on OCT the treatment interval to the next visit is reduced by 2 weeks. The minimum treatment interval is 4 weeks, the maximum treatment interval is 12 weeks.	at 32 weeks and 56 weeks
Maximum extended treatment interval without retinal (intra- and subretinal) fluid	Treatment is administered at each visit. The interval between treatments is based on a treat and extend regime. The first interval between treatments, from baseline, is 4 weeks. Intra- and subretinal fluid are assessed at each visit with optical coherence tomography (OCT). Should no intra- and subretinal fluid be present on OCT, the treatment interval to the next visit is extended by 2 weeks. Is intra- and or subretinal fluid present on OCT the treatment interval to the next visit is reduced by 2 weeks. The minimum treatment interval is 4 weeks, the maximum treatment interval is 12 weeks.	at 32 weeks and 56 weeks
Number of injections received		during 32 weeks and 1 year
Proportion of eyes remaining on a 4-weekly interval from baseline to last visit (completed interval)	Treatment is administered at each visit. The interval between treatments is based on a treat and extend regime. The first interval between treatments, from baseline, is 4 weeks. Intra- and subretinal fluid are assessed at each visit with optical coherence tomography (OCT). Should no intra- and subretinal fluid be present on OCT, the treatment interval to the next visit is extended by 2 weeks. Is intra- and or subretinal fluid present on OCT the treatment interval to the next visit is reduced by 2 weeks. The minimum treatment interval is 4 weeks, the maximum treatment interval is 12 weeks.	at 32 weeks and 56 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean change in ETDRS letter score	Best Corrected Visual Acuity (BCVA) is measured via Early Treatment Diabetic Retinopathy Severity (ETDRS) charts. The ETDRS letter score ranges from 0 to 100 (best score).	from baseline to an averaged EDTRS letter score between 24-32 weeks and between 48-56 weeks
Mean averaged ETDRS letter score	Best Corrected Visual Acuity (BCVA) is measured via Early Treatment Diabetic Retinopathy Severity (ETDRS) charts. The ETDRS letter score ranges from 0 to 100 (best score).	between 24-32 weeks and between 48-56 weeks
Proportion of eyes gaining ≥ 5 EDTRS letters		from baseline to an averaged ETDRS letter score between 24-32 weeks and between 48-56 weeks
Proportion of eyes loosing ≥5 EDTRS letters		from baseline to an averaged ETDRS letter score between 24-32 weeks and between 48-56 weeks
Mean change in low-luminance Best Corrected Visual Acuity (BCVA)		from baseline to last visit at or before 32 weeks and last visit at or before 56 weeks
Mean change in central subfield thickness (CST)	CST is measured using optical coherence tomography (OCT).	from baseline to an averaged CST between 24-32 weeks and between 48-56 weeks
Proportion of eyes with no intraretinal fluid	Intraretinal fluid is assessed via optical coherence tomography (OCT).	at baseline, last visit at or before 32 weeks and at or before 56 weeks
Proportion of eyes with no subretinal fluid	Subretinal fluid is assessed via optical coherence tomography (OCT).	at baseline, last visit at or before 32 weeks and at or before 56 weeks
Proportion of eyes with no intra- and subretinal fluid	Intra- and subretinal fluid is assessed via optical coherence tomography (OCT).	at baseline, last visit at or before 32 weeks and at or before 56 weeks
Retinal nerve fiber layer (RNFL) thickness	RNFL thickness is assessed via optical coherence tomography (OCT).	at baseline, last visit at or before 32 weeks and last visit at or before 56 weeks
Concentration of plasma vascular endothelial growth factor A (VEGF-A) and Angiopoietin-2 (Ang-2)	Plasma VEGF-A and Ang-2 is determined using a validated enzyme-linked immunosorbent assay (ELISA).	at baseline, one week after baseline, four weeks after baseline and last visit at or before 32 weeks
Patient-reported vision-related functioning and quality of life	Patient-reported vision-related functioning and quality of life is assessed via National Eye Institute Visual Function Questionnaire (VFQ-25). VFQ-25 score ranges from 0 to 100 (highest score).	at screening, last visit at or before 32 weeks and last visit at or before 56 weeks
Presence of safety outcomes	Rates of adverse events (AE's) and serious adverse events (SAE's) are given.	from baseline through to week 56

Collaborators and Investigators

• Sponsor: Medical University of Graz
• Investigators: Principal Investigator: Andreas Wedrich, MD, Department of Ophthalmology, Medical University Graz

Study record dates

Study Major Dates

• Study Start (Actual): July 4, 2023
• Primary Completion (Estimated): October 1, 2024
• Study Completion (Estimated): February 1, 2025

Study Registration Dates

• First Submitted: June 19, 2023
• First Submitted That Met QC Criteria: July 3, 2023
• First Posted (Actual): July 12, 2023

Study Record Updates

• Last Update Posted (Estimated): January 18, 2024
• Last Update Submitted That Met QC Criteria: January 17, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: AMD; neovascular age-related macular degeneration; aflibercept; nAMD; faricimab; treat and extend
• 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; Faricimab
• Other Study ID Numbers: 35-200 ex 22/23; 2023-000037-32 (EudraCT Number)

Drug and device information, study documents

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