Clinical trial NCT05941715: Faricimab for High-frequent Aflibercept Treated Neovascular Age-related Macular Degeneration
Official title: Faricimab for High-frequent Aflibercept Treated Neovascular Age-related Macular Degeneration: a Monocenter, Randomized, Double-masked Comparator-controlled Study (FAN)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Neovascular Age-related Macular Degeneration
Keywords: aflibercept
faricimab
treat and extend
nAMD
AMD
neovascular age-related macular degeneration
Lead sponsor: Medical University of Graz
Sponsor class: OTHER
First posted: 2023-07-12
Enrollment: 70
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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).

Eligibility criteria: 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

Primary outcomes:
measure: 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)
timeFrame: at 32 weeks
Secondary outcomes:
measure: Proportion of eyes with maximum extended interval without retinal (intra- and subretinal) fluid of ≥ 6, ≥ 8, ≥ 10 weeks and (≥ 12weeks)
timeFrame: at 32 weeks and 56 weeks
measure: Maximum extended treatment interval without retinal (intra- and subretinal) fluid
timeFrame: at 32 weeks and 56 weeks
measure: Number of injections received
timeFrame: during 32 weeks and 1 year
measure: Proportion of eyes remaining on a 4-weekly interval from baseline to last visit (completed interval)
timeFrame: at 32 weeks and 56 weeks
Other outcomes:
measure: Mean change in ETDRS letter score
timeFrame: from baseline to an averaged EDTRS letter score between 24-32 weeks and between 48-56 weeks
measure: Mean averaged ETDRS letter score
timeFrame: between 24-32 weeks and between 48-56 weeks
measure: Proportion of eyes gaining ≥ 5 EDTRS letters
timeFrame: from baseline to an averaged ETDRS letter score between 24-32 weeks and between 48-56 weeks
measure: Proportion of eyes loosing ≥5 EDTRS letters
timeFrame: from baseline to an averaged ETDRS letter score between 24-32 weeks and between 48-56 weeks
measure: Mean change in low-luminance Best Corrected Visual Acuity (BCVA)
timeFrame: from baseline to last visit at or before 32 weeks and last visit at or before 56 weeks
measure: Mean change in central subfield thickness (CST)
timeFrame: from baseline to an averaged CST between 24-32 weeks and between 48-56 weeks
measure: Proportion of eyes with no intraretinal fluid
timeFrame: at baseline, last visit at or before 32 weeks and at or before 56 weeks
measure: Proportion of eyes with no subretinal fluid
timeFrame: at baseline, last visit at or before 32 weeks and at or before 56 weeks
measure: Proportion of eyes with no intra- and subretinal fluid
timeFrame: at baseline, last visit at or before 32 weeks and at or before 56 weeks
measure: Retinal nerve fiber layer (RNFL) thickness
timeFrame: at baseline, last visit at or before 32 weeks and last visit at or before 56 weeks
measure: Concentration of plasma vascular endothelial growth factor A (VEGF-A) and Angiopoietin-2 (Ang-2)
timeFrame: at baseline, one week after baseline, four weeks after baseline and last visit at or before 32 weeks
measure: Patient-reported vision-related functioning and quality of life
timeFrame: at screening, last visit at or before 32 weeks and last visit at or before 56 weeks
measure: Presence of safety outcomes
timeFrame: from baseline through to week 56
Locations:
city: Graz
country: Austria
facility: Department of Ophthalmolgy, Medical University Graz
state: Styria
Study officials:
affiliation: Department of Ophthalmology, Medical University Graz
name: Andreas Wedrich, MD
role: PRINCIPAL_INVESTIGATOR
References: