The goal of this clinical trial is to assess the efficacy, safety and durability of faricimab in caucasian patients with polypoidal choroidal vasculopathy (PCV). The main question it aims to answer is: To evaluate the efficacy of intravitreal (IVT) injections of faricimab 6 milligrams (mg) on Best Corrected Visual Acuity (BCVA) outcomes in caucasian patients with symptomatic macular PCV. Participants will undergo ophthalmic examination, safety assessment and treatment with faricimab according to a patient specific treat and extend regimen.
Polypoidal choroidal vasculopathy (PCV) was first described in 1982 by Yannuzzi as a choroidal vasculopathy leading to haemorrhagic and exudative macular degeneration. More than four decades later, the pathogenesis of the disease remains uncertain with authors considering PCV a subtype of neovascular age-related macular degeneration (nAMD) while others advocate a separate clinical entity and adequate treatment is still an unmet need. Several studies have reported an association between PCV and major and minor interethnic classification differences regarding morphological alterations, prevalence, genetic associations, lesion location, and results after anti-vascular endothelial growth factor (VEGF) treatment, among others. For instance, the reported prevalence of PCV in patients with neovascular AMD ranges from 4% to 9,8% in Caucasians and from 22% to 55% in Asians. However, a recent study reported a much higher prevalence in Caucasians (22,1%), suggesting that PCV may actually be underdiagnosed in this population. Today, intravitreal (IVT) anti-VEGF therapy plays a key role in the management of PCV and has become the standard of care. The anti-permeability property of anti-VEGF agents, such as aflibercept and ranibizumab, play a role in reducing the exudation from abnormal choroidal vessels and polypoidal lesions, thereby decreasing the subretinal fluid and preserving vision. Although the current standard of care has demonstrated clinical benefit for patients with PCV, many limitations exist in understanding the disease as a result of its heterogeneity in clinical features and treatment outcomes. The burden of frequent injections, incomplete polypoidal lesion closure, and the risk and unpredictability of lesion relapse reinforce the need to develop new treatments for patients with PCV. This population is at risk of disease relapse, retinal haemorrhage, and vision loss, and is appropriate for inclusion in this clinical trial. Faricimab is a novel humanized bispecific Immunoglobulin G1 (IgG1) monoclonal antibody that selectively binds with high affinity to VEGF-A and angiopoietin-2 (Ang-2). Faricimab was studied for the treatment of neovascular AMD (nAMD) in the global Phase III Studies TENAYA (ClinicalTrials.gov identifier: NCT03823287) and LUCERNE (ClinicalTrials.gov identifier: NCT03823300) and is currently being studied in the long-term extension Study AVONELLE-X (ClinicalTrials.gov identifier: NCT04777201). The TENAYA (ClinicalTrials.gov identifier: NCT03823287) and LUCERNE (ClinicalTrials.gov identifier: NCT03823300) studies consistently showed that faricimab, given at intervals of up to 16 weeks, offered non-inferior vision gains compared with aflibercept, given every 2 months in the first year. Approximately 50% of participants eligible for extended dosing with faricimab were able to be treated every 4 months, and nearly 80% of participants every 3 months or longer. However, patients with symptomatic macular PCV were under-represented in the faricimab Phase III pivotal Studies TENAYA (ClinicalTrials.gov identifier: NCT03823287) and LUCERNE (ClinicalTrials.gov identifier: NCT03823300). The purpose of this study is to assess the efficacy, durability, and safety of faricimab 6 mg IVT administered at up to 24-week intervals in the treatment-naive study eye of Caucasian patients with symptomatic macular PCV. This study will add to the evidence base for the benefit-risk profile of faricimab IVT injection in Caucasian patients with symptomatic macular PCV. The study consists of a screening period of up to 28 days (Days -28 to -1) in length and an approximately 100-week study treatment period consisting of a Treatment Initiation period (Weeks 1-12) and the treat and extend (T\&E) regimen period (Weeks 20-Week 100).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
120
The investigational medicinal product (IMP) for this study is faricimab (RO6867461), as per clinical practice. No control treatment will be used for this study
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico-Clinica Regina Elena
Milan, Italy
NOT_YET_RECRUITINGMedical Retina Service, Operative Unit Ophthalmology - MultiMedica Spa (IRCCSMM)
Milan, Italy
NOT_YET_RECRUITINGASST-Fatebenefratelli-Sacco P.O.L. Sacco
Milan, Italy
NOT_YET_RECRUITINGEye Unit, University Hospital Maggiore della Carità
Novara, Italy
Change from Baseline in BCVA in the study eye to Week 40 or 44 or 48
Best Corrected Visual Acuity (BCVA) is measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity.
Time frame: From Baseline through Week 40 or 44 or 48
Change from Baseline in BCVA in the Study
Best Corrected Visual Acuity (BCVA) is measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart
Time frame: From baseline through last treatment visit (up to 100 weeks)
Change from Baseline in BCVA in the Study Eye to the last treatment visit
At a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity.
Time frame: From Baseline through last treatment visit (up to 100 weeks)
Change From Baseline in BCVA in the Study Eye Over Time
Best Corrected Visual Acuity (BCVA) is measured on the ETDRS chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity.
Time frame: Over time (up to 104 weeks)
Proportion of Participants Gaining Greater Than or Equal to (≥)15, ≥10, or ≥5 Letters from the Baseline BCVA in the Study Eye Averaged Over Time
Best Corrected Visual Acuity (BCVA) is measured on the ETDRS chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity.
Time frame: Over time (up to 104 weeks)
Proportion of Participants Avoiding a Loss of ≥15, ≥10, or ≥5 Letters from the Baseline BCVA in the Study Eye Over Time
Best Corrected Visual Acuity (BCVA) is measured on the ETDRS chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score) and avoiding a loss in BCVA from baseline indicates no worsening in visual acuity.
Time frame: Over time (up to 104 weeks)
Percentage of Participants Maintaining or Achieving BCVA Snellen Equivalent of 20/40 (BCVA =69 Letters) in the Study Eye
Best Corrected Visual Acuity (BCVA) was measured on the ETDRS chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity.
Time frame: Over time (up to 104 weeks)
Proportion of participants with complete polypoidal lesion regressions at Weeks 40, 44, or 48
Complete polypoidal lesions regressions are measured using Indocyanine Green Angiography (ICGA), as assessed by the central reading center.
Time frame: From Baseline through Week 40 or 44 or 48
Proportion of participants with complete polypoidal lesion regressions at the end of the study
Complete polypoidal lesions regressions are measured using Indocyanine Green Angiography (ICGA), as assessed by the central reading center.
Time frame: From Baseline through the end of the study (up to 104 weeks)
Change From Baseline in Central Subfield Thickness in the Study Eye at Weeks 40 or 44, or 48
Central subfield thickness (CST) is defined as the distance between the internal limiting membrane (ILM) and the retinal pigment epithelium (RPE) using optical coherence tomography (OCT), as assessed by the central reading center.
Time frame: From Baseline through Week 40 or 44 or 48
Change from Baseline in Central Subfield Thickness in the Study Eye to the end of the study
Central subfield thickness (CST) is defined as the distance between the ILM and the RPE using OCT, as assessed by the central reading center.
Time frame: From Baseline through the end of the study (up to 104 weeks)
Change From Baseline in Central Subfield Thickness in the Study Eye Over Time
Central subfield thickness (CST) is defined as the distance between the ILM and the RPE using OCT, as assessed by the central reading center.
Time frame: Over time (up to 104 weeks)
Proportion of Participants With no Intraretinal Fluid and no subretinal fluid in the Study Eye at Week 20
Intraretinal fluid and subretinal fluid are measured using OCT in the central subfield (center 1 millimetre \[mm\]).
Time frame: From Baseline and Week 20
Proportion of Participants With no Intraretinal Fluid and no subretinal fluid in the Study Eye at Weeks 40 or 44, or 48
Intraretinal fluid and subretinal fluid are measured using OCT in the central subfield (center 1 mm).
Time frame: From Baseline and Week 40 or 44 or 48
Proportion of Participants With no Intraretinal Fluid and no subretinal fluid in the Study Eye at the end of the study
Intraretinal fluid and subretinal fluid are measured using OCT in the central subfield (center 1 mm).
Time frame: From Baseline and the end of the study (up to 104 weeks)
Proportion of Participants With no Intraretinal Fluid, no Subretinal Fluid and no sub-RPE fluid in the Study Eye at Week 20
Intraretinal fluid, subretinal fluid and sub-RPE fluid are measured using OCT in the central subfield (center 1 mm).
Time frame: From Baseline and Week 20
Proportion of Participants With no Intraretinal Fluid, no Subretinal Fluid and no sub-RPE fluid in the Study Eye at Weeks 40 or 44, or 48
Intraretinal fluid, subretinal fluid and sub-RPE fluid are measured using OCT in the central subfield (center 1 mm).
Time frame: From Baseline and Week 40 or 44 or 48
Proportion of Participants With no Intraretinal Fluid, no Subretinal Fluid and no sub-RPE fluid in the Study Eye at the end of the study
Intraretinal fluid, subretinal fluid and sub-RPE fluid are measured using OCT in the central subfield (center 1 mm).
Time frame: From Baseline and the end of the study (up to 104 weeks)
Change From Baseline in branch Neovascularization network in the Study Eye at 1 year
The branch neovascularization network in the study eye is evaluated by a central reading center using OCT angiography (OCTA).
Time frame: Baseline and 1 year
Change From Baseline in branch Neovascularization network in the Study Eye at 2 years
The branch neovascularization network in the study eye is evaluated by a central reading center using OCT angiography (OCTA).
Time frame: Baseline and 2 years
Proportion of participants on 12 weeks or more treatment intervals at the end of the study.
Proportions are based on the number of participants who have not discontinued the study at the end of the study. The treatment interval at a given visit is defined as the treatment interval decision followed at that visit.
Time frame: End of study (up to 100 weeks)
Number of faricimab injections received from Week 20 until the end of the study.
Count of the number of faricimab injections each participant received after the treatment initiation period (baseline to week 12).
Time frame: Week 20 through end of study (up to 100 weeks)
Incidence and severity of ocular adverse events
This analysis of adverse events (AEs) only includes ocular AEs. Investigators sought information on AEs at each contact with the participants. All AEs are recorded and the investigator made an assessment of seriousness, severity, and causality of each AE.
Time frame: From first dose of study drug through end of study (up to 104 weeks)
Incidence and severity of Non-Ocular Adverse Event
This analysis of AEs only includes non-ocular (systemic) AEs. Multiple occurrences of the same AE in one individual are counted only once. Investigators sought information on AEs at each contact with the participants. All AEs were recorded and the investigator made an assessment of seriousness, severity, and causality of each AE.
Time frame: From first dose of study drug through end of study (up to 104 weeks)
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IRCCS Fondazione G.B. Bietti per lo Studio e la Ricerca in Oftalmologia ONLUS,
Roma, Italy
RECRUITINGDepartment of Ophthalmology, University Vita Salute - Scientific Institute of San Raffaele
San Raffaele, Italy
NOT_YET_RECRUITINGDepartment of Ophthalmology, University of Udine
Udine, Italy
NOT_YET_RECRUITINGEspaço Médico de Coimbra
Coimbra, Portugal
RECRUITINGOphthalmology Department, Hospitais Universidade de Coimbra,
Coimbra, Portugal
RECRUITINGUnidade Local de Saúde da Região de Leiria, E.P.E.
Leiria, Portugal
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