Efficacy, Safety, and Durability of Faricimab in Caucasian Patients with Polypoidal Choroidal Vasculopathy: A Phase IV, Multicentre, Open-Label Study

Trial ID: 2024-515640-22-00
Protocol: ECR-AMD-2024-15
Sponsor: Association For Innovation And Biomedical Research On Light And Image

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Diseases & Conditions

Polypoidal choroidal vasculopathy

Objectives

The primary objective of this study is to evaluate the **efficacy** of intravitreal (IVT) injections of faricimab on Best Corrected Visual Acuity (BCVA) outcomes in Caucasian patients with symptomatic macular **polypoidal choroidal vasculopathy** (PCV). This is clinically relevant as BCVA is a critical measure of visual function, and improvements in BCVA can significantly impact the quality of life for patients with PCV.

Secondary objectives include:

Evaluating the efficacy of IVT injections of faricimab on additional BCVA outcomes.
Assessing the efficacy on anatomic outcome measures using Indocyanine Green Angiography (ICGA), Optical Coherence Tomography (OCT), and Optical Coherence Tomography Angiography (OCTA).
Determining the durability of IVT injections of faricimab.
Evaluating the ocular and non-ocular safety and tolerability of IVT injections of faricimab.

Participants

The clinical trial involves a total of **30 participants** diagnosed with **polypoidal choroidal vasculopathy**. The study population includes both male and female subjects, all of whom are **Caucasian** and aged 50 years or older. Participants were selected based on their ability to comply with the study protocol, as judged by the investigator. The trial does not include any vulnerable populations. Lifestyle considerations such as diet, physical activity, or habits are not specified. Key inclusion criteria require participants to have sufficiently clear ocular media and adequate pupillary dilatation for retinal imaging, as well as a confirmed diagnosis of symptomatic macular polypoidal choroidal vasculopathy. The study aims to evaluate the efficacy of intravitreal injections of faricimab on Best Corrected Visual Acuity outcomes in this specific patient group.

Plans and Procedures

The clinical trial is a **phase IV** study designed to evaluate the efficacy, safety, and durability of **faricimab** in patients with **polypoidal choroidal vasculopathy**. This open-label, single-arm study will involve intravitreal injections of faricimab, with the primary objective being the assessment of changes in Best Corrected Visual Acuity (BCVA) outcomes. The trial is expected to commence recruitment on July 1, 2025, and conclude by July 31, 2028, with a maximum treatment period of 100 weeks for each participant.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, ethnicity, and ocular health. The inclusion criteria require participants to be Caucasian, aged 50 years or older, and capable of complying with the study protocol. The study eye must have a confirmed diagnosis of symptomatic macular polypoidal choroidal vasculopathy, with specific visual acuity requirements. Following the screening, participants will receive regular follow-up visits to monitor BCVA changes and other ocular health parameters. The primary endpoint will be the change in BCVA from baseline at weeks 40, 44, or 48, with secondary endpoints including BCVA changes over time and the proportion of participants achieving specific visual acuity improvements.

The expected length of participant involvement is up to 100 weeks, with conditions for early termination including non-compliance with the study protocol or the occurrence of adverse events that compromise participant safety. The study will also assess the incidence and severity of both ocular and non-ocular adverse events. The trial design does not include a control group, as it is a single-arm study, and participants will not be blinded to the treatment. The study aims to provide valuable insights into the long-term effects of faricimab on visual acuity and ocular health in this patient population.

Treatment

The clinical trial involves the administration of **faricimab**, marketed under the name Vabysmo, which is a **solution for injection**. The pharmaceutical form is specifically designed for **intravitreal use**, meaning it is injected directly into the eye. The concentration of the solution is 120 mg/mL. The maximum daily and total dose is 120 mg/mL, and the treatment period extends up to 100 days. Faricimab is a bispecific antibody targeting both vascular endothelial growth factor A (VEGF-A) and angiopoietin 2 (Ang-2), and it is classified under the ATC code S01LA09. The active substance is derived from a protein of other origin, specifically a recombinant human anti-human VEGF-A and anti-human Ang-2 monoclonal antibody. The product is not a pediatric formulation and is not classified as an orphan drug.

No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are utilized in this study. The trial is designed as a single-arm study, focusing solely on the efficacy, safety, and durability of faricimab in patients with polypoidal choroidal vasculopathy. Compliance with the dosing schedule is monitored throughout the study period to ensure adherence to the treatment protocol. The study aims to evaluate the impact of faricimab on Best Corrected Visual Acuity (BCVA) outcomes in the target patient population.

Efficacy

Efficacy in this clinical trial will be assessed by evaluating the impact of intravitreal injections of **faricimab** on Best Corrected Visual Acuity (BCVA) outcomes in patients with symptomatic macular polypoidal choroidal vasculopathy (PCV). The primary endpoint is the change from baseline in BCVA, as measured on the Early Treatment of Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters, at Weeks 40, 44, or 48. Secondary endpoints include changes from baseline in BCVA to the last treatment visit, over time, and the proportion of participants gaining or avoiding loss of ≥ 15, ≥ 10, or ≥ 5 letters in BCVA from baseline over time. Additionally, the percentage of participants maintaining or achieving a BCVA of 20/40 (69 letters) will be evaluated.

Further assessments will include the proportion of participants with complete polypoidal lesion regressions at specified weeks and at the end of the study, changes from baseline in central subfield thickness (CST) at specified weeks and over time, and the proportion of participants with no intraretinal fluid, subretinal fluid, or sub-RPE fluid at specified weeks and at the end of the study. The change from baseline in branch neovascular network size at 1 and 2 years, the proportion of participants on 12 weeks or more treatment intervals at the end of the study, and the number of faricimab injections received from Week 20 until the end of the study will also be analyzed. Incidence and severity of ocular and non-ocular adverse events will be monitored throughout the trial.

Inclusion and Exclusion Criteria

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Inclusion Criteria

General Inclusion Criteria: Potential participants are eligible to be included in the study only if all of the following criteria apply: - Signed informed consent form (ICF) - Age ≥ 50 years at the time of signing the ICF - Caucasian - Participants who are able to comply with the study protocol, in the investigator’s judgment - For female participants of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception.
Ocular Inclusion Criteria for study eye: - Sufficiently clear ocular media and adequate pupillary dilatation to allow acquisition of good quality retinal images to confirm diagnosis. - Confirmed diagnosis, by the Reading Centre, of naïve symptomatic macular PCV defined by the following: Active macular polypoidal lesions shown by ICGA AND Presence of exudative or haemorrhagic features involving the macula as identified by the investigator using multimodal images. - BCVA scores of 78-24 ETDRS letters, inclusive (20/32 to 20/320 approximate Snellen equivalent), using the ETDRS protocol and assessed at the initial testing distance of 4 meters on study Day 1.

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Exclusion Criteria

General Exclusion Criteria: Potential participants are excluded from the study if any of the following criteria apply: - Treatment with investigational therapy (device, drug, or traditional medicine with the exception of vitamins and minerals) within 3 months prior to initiation of study treatment on study Day 1. - Any major illness or major surgical procedure within 1 month before screening. - Active cancer within the 12 months prior to study Day 1 except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, and prostate cancer with a Gleason score of ≤ 6 (Grade Group of 1) and a stable prostate-specific antigen for ≥ 12 months. - Continuous use of any of the following medications and treatments: Systemic anti-VEGF therapy, Systemic drugs known to cause macular oedema (fingolimod, tamoxifen), Other experimental therapies (except those comprising vitamins and minerals) and therapies that claim to have an effect on macular pathology (e.g., kallidinogenase). - Systemic treatment for suspected or active systemic infection on study Day 1. - Ongoing use of prophylactic antibiotic therapy may be acceptable after discussion with the Medical Monitor. - Uncontrolled blood pressure, defined as systolic blood pressure > 180 mmHg and/or diastolic blood pressure > 100 mmHg while the participant is at rest on study Day 1. - History of stroke (cerebral vascular accident) or myocardial infarction within 6 months prior to study Day 1. - History of other diseases, metabolic dysfunction, physical examination finding, or historical or current clinical laboratory findings giving reasonable suspicion of a condition that contraindicates the use of the IMP or that might affect the interpretation of the results of the study or renders the participant at high risk for treatment complications in the opinion of the investigator. - History of severe allergic reaction or anaphylactic reaction to a biologic agent or known hypersensitivity to any component of the faricimab injection, study-related procedure preparations (including fluorescein and indocyanine green dyes), dilating drops, or any of the anaesthetic and antimicrobial preparations used by a participant during the study. - Pregnancy or breastfeeding, or intention of becoming pregnant during the study or within 3 months after the final dose of faricimab.
Ocular Exclusion Criteria: Potential participants are excluded from the study if any of the following criteria apply to both eyes: - History of idiopathic or autoimmune-associated uveitis in either eye. - Active ocular inflammation or suspected or active ocular or periocular infection in either eye on study Day 1.
Ocular exclusion criteria for study eye: Participants who meet any of the following ocular criteria for the study eye will be excluded from study entry: - Any history or presence of macular pathology unrelated to PCV affecting vision or contributing to the presence of macular haemorrhage, IRF, or SRF. - Retinal pigment epithelial tear involving the macula on study Day 1. - Diagnosis with or suspected of having narrow-angle glaucoma who have not undergone iridotomy. The inclusion of these patients will be conditional upon prior referral to the relevant specialist for appropriate treatment to enable participation in the study. - On FFA/colour fundus photograph (CFP): Subretinal haemorrhage of > 4 macular photocoagulation study disc area and/or that involves the fovea; Fibrosis or atrophy of > 50% of the total lesion area and/or that involves the fovea; aculopathy, or epiretinal membrane with traction) Any concurrent intraocular condition (e.g., amblyopia, aphakia, retinal detachment, cataract, diabetic retinopathy or mthat, in the opinion of the investigator, could either reduce the potential for visual improvement or require medical or surgical intervention during the study; Current vitreous haemorrhage on study Day 1; Advanced and/or uncontrolled glaucoma; Spherical equivalent of refractive error demonstrating more than 8 dioptres of myopia. - Any prior or concomitant treatment for PCV or other retinal diseases, including, but not restricted to, IVT treatment (e.g., faricimab, anti-VEGF, steroids, tissue plasminogen activator, ocriplasmin, C3F8, air), periocular pharmacological intervention, argon laser photocoagulation, verteporfin PDT, diode laser, transpupillary thermotherapy, or ocular surgical intervention. - Any cataract surgery or treatment for complications of cataract surgery with steroids or yttrium-aluminum-garnet (YAG) laser capsulotomy within 3 months prior to study Day 1. - Any other intraocular surgery (e.g., pars plana vitrectomy, glaucoma surgery, corneal transplant, or radiotherapy). - Prior periocular pharmacological or IVT treatment (including anti-VEGF medication) for other retinal diseases. - Continuous use of any of the following medications and treatments: IVT anti-VEGF agents (other than study-assigned faricimab); IVT, periocular (subtenon) corticosteroids, steroid implants (i.e., Ozurdex®, Illuvien®), or chronic topical ocular corticosteroids (defined as continuous usage for 100 days or longer); Concurrent use of any macular photocoagulation or PDT with verteporfin.
Participants who have a non-functioning fellow (non-study) eye, defined as either BCVA of hand motion or worse, or no physical presence of non-study eye (i.e., monocular), at both the screening and study Day 1 visits will be excluded from study entry.