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

Study Overview
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Brief Summary
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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
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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).

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

Conditions
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Neovascular Age-related Macular Degeneration

Intervention / Treatment
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* Drug: Aflibercept 40 MG/ML
* Drug: Faricimab 120 MG/ML


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: group A: aflibercept first (part 1), switch to faricimab (part 2)<br>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<br>* treat-and-extend<br>* Other names: Eylea®;Drug: Faricimab 120 MG/ML<br>* treat-and-extend<br>* Other names: Vabysmo®;|
| Experimental: group B: faricimab monotherapy<br>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<br>* treat-and-extend<br>* Other names: Vabysmo®;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AMD, aflibercept, faricimab, treat and extend, nAMD, neovascular age-related macular degeneration