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

Sponsor

Medical University of Graz (Other)

Overall Status

Recruiting

CT.gov ID

NCT05941715

Collaborator

(none)

Enrollment

Location

Arms

17.1

Anticipated Duration (Months)

4.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Neovascular Age-related Macular Degeneration	Drug: Aflibercept 40 MG/ML Drug: Faricimab 120 MG/ML	Phase 4

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 Design

Study Type:

Interventional

Anticipated Enrollment :

70 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Jul 1, 2023

Anticipated Primary Completion Date :

Jun 1, 2024

Anticipated Study Completion Date :

Dec 1, 2024

Arms and Interventions

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®

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®

Outcome Measures

Primary Outcome Measures

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) [at 32 weeks]

Secondary Outcome Measures

proportion of eyes with maximum extended interval without retinal (intra- and subretinal) fluid of ≥ 6, ≥ 8, ≥ 10 weeks and (≥ 12weeks) [at 32 weeks and 56 weeks]
maximum extended treatment interval without retinal (intra- and subretinal) fluid [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) [at 32 weeks and 56 weeks]

Other Outcome Measures

mean change in ETDRS letter score [from baseline to an averaged EDTRS letter score between 24-32 weeks and between 48-56 weeks]
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)
mean averaged ETDRS letter score [between 24-32 weeks and between 48-56 weeks]
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)
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) [from baseline to an averaged CST between 24-32 weeks and between 48-56 weeks]
CST is measured using optical coherence tomography (OCT)
proportion of eyes with no intraretinal fluid [at baseline, last visit at or before 32 weeks and at or before 56 weeks]
intraretinal fluid is assessed via optical coherence tomography (OCT)
proportion of eyes with no subretinal fluid [at baseline, last visit at or before 32 weeks and at or before 56 weeks]
subretinal fluid is assessed via optical coherence tomography (OCT)
proportion of eyes with no intra- and subretinal fluid [at baseline, last visit at or before 32 weeks and at or before 56 weeks]
intra- and subretinal fluid is assessed via optical coherence tomography (OCT)
retinal nerve fiber layer (RNFL) thickness [at baseline, last visit at or before 32 weeks and last visit at or before 56 weeks]
RNFL thickness is assessed via optical coherence tomography (OCT)
concentration of plasma vascular endothelial growth factor A (VEGF-A) [at baseline, one week after baseline, four weeks after baseline and last visit at or before 32 weeks]
plasma VEGF-A is determined using a validated enzyme-linked immunosorbent assay (ELISA)
concentration of Angiopoietin-2 (Ang-2) [at baseline, one week after baseline, four weeks after baseline and last visit at or before 32 weeks]
Ang-2 is determined using a validated enzyme-linked immunosorbent assay (ELISA)
patient-reported vision-related functioning and quality of life [at screening, last visit at or before 32 weeks and last visit at or before 56 weeks]
via National Eye Institute Visual Function Questionnaire (VFQ-25). VFQ-25 score ranges from 0 to 100 (highest score)
presence of safety outcomes [from baseline through to week 56]
rates of adverse events (AE's) and serious adverse events (SAE's)

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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