Neovascular Age-related Macular Degeneration
Conditions
Keywords
aflibercept, faricimab, treat and extend, nAMD, AMD, neovascular age-related macular degeneration
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).
Interventions
DRUGAflibercept 40 MG/ML
treat-and-extend
DRUGFaricimab 120 MG/ML
treat-and-extend
Sponsors
Medical University of Graz
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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. |
| Maximum extended treatment interval without retinal (intra- and subretinal) fluid | at 32 weeks and 56 weeks | 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. |
| 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 | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| 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) and Angiopoietin-2 (Ang-2) | at baseline, one week after baseline, four weeks after baseline and last visit at or before 32 weeks | Plasma VEGF-A and 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 | 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). |
| Presence of safety outcomes | from baseline through to week 56 | Rates of adverse events (AE's) and serious adverse events (SAE's) are given. |
| 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). |
| 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 | — |
Countries
Austria
Outcome results
None listed