Polypoidal Choroidal Vasculopathy
Conditions
Keywords
Faricimab, Caucasian patients, PCV, Durability, Safety, Efficacy
Brief summary
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.
Detailed description
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).
Interventions
The investigational medicinal product (IMP) for this study is faricimab (RO6867461), as per clinical practice. No control treatment will be used for this study
Sponsors
Association for Innovation and Biomedical Research on Light and Image
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This study will be conducted in adult Caucasian participants with symptomatic macular PCV, a subtype of nAMD, which was under-represented in the faricimab Phase III pivotal Studies TENAYA (ClinicalTrials.gov identifier: NCT03823287) and LUCERNE (ClinicalTrials.gov identifier: NCT03823300) where less than 2% of the enrolled participants with nAMD were diagnosed with PCV and no Caucasian participants with symptomatic macular PCV were identified in the mentioned pivotal Studies.
Eligibility
Sex/Gender
ALL
Age
50 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
General Inclusion Criteria: Potential participants are eligible to be included in the study only if all of the following criteria apply: * Signed 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 as defined below: Female participants must remain abstinent or use contraceptive methods with a failure rate of \< 1% per year, during the treatment period and for at least 3 months after the final dose of faricimab. A female participant is considered to be of childbearing potential if she is post-menarche, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and is not permanently infertile due to surgery (i.e., removal of ovaries, fallopian tubes, and/or uterus) or another cause as determined by the investigator (e.g., Müllerian agenesis). Per this definition, a female participant with a tubal ligation is considered to be of childbearing potential. The definition of childbearing potential may be adapted for alignment with local guidelines or regulations. Examples of contraceptive methods with a failure rate of \< 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices. The reliability of sexual abstinence should be evaluated concerning the duration of the clinical trial and the preferred and usual lifestyle of the individual. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post-ovulation methods) and withdrawal are not adequate methods of contraception. If required per local guidelines or regulations, locally recognized adequate methods of contraception and information about the reliability of abstinence will be described in the local ICF. 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 \[see the BCVA Standard Operational Procedures (SOP) for additional details\] on study Day 1. 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 medications and treatments indicated below: * 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 28 days after the final dose of faricimab Ocular
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline in BCVA in the study eye to Week 40 or 44 or 48 | From Baseline through 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline in BCVA in the Study | From baseline through last treatment visit (up to 100 weeks) | Best Corrected Visual Acuity (BCVA) is measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart |
| Change from Baseline in BCVA in the Study Eye to the last treatment visit | From Baseline through last treatment visit (up to 100 weeks) | 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. |
| Change From Baseline in BCVA in the Study Eye Over Time | Over time (up to 104 weeks) | 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. |
| 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 | Over time (up to 104 weeks) | 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. |
| Proportion of Participants Avoiding a Loss of ≥15, ≥10, or ≥5 Letters from the Baseline BCVA in the Study Eye Over Time | Over time (up to 104 weeks) | 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. |
| Percentage of Participants Maintaining or Achieving BCVA Snellen Equivalent of 20/40 (BCVA =69 Letters) in the Study Eye | Over time (up to 104 weeks) | 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. |
| Proportion of participants with complete polypoidal lesion regressions at Weeks 40, 44, or 48 | From Baseline through Week 40 or 44 or 48 | Complete polypoidal lesions regressions are measured using Indocyanine Green Angiography (ICGA), as assessed by the central reading center. |
| Proportion of participants with complete polypoidal lesion regressions at the end of the study | From Baseline through the end of the study (up to 104 weeks) | Complete polypoidal lesions regressions are measured using Indocyanine Green Angiography (ICGA), as assessed by the central reading center. |
| Change From Baseline in Central Subfield Thickness in the Study Eye at Weeks 40 or 44, or 48 | From Baseline through Week 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. |
| Change from Baseline in Central Subfield Thickness in the Study Eye to the end of the study | From Baseline through the end of the study (up to 104 weeks) | Central subfield thickness (CST) is defined as the distance between the ILM and the RPE using OCT, as assessed by the central reading center. |
| Change From Baseline in Central Subfield Thickness in the Study Eye Over Time | Over time (up to 104 weeks) | Central subfield thickness (CST) is defined as the distance between the ILM and the RPE using OCT, as assessed by the central reading center. |
| Proportion of Participants With no Intraretinal Fluid and no subretinal fluid in the Study Eye at Week 20 | From Baseline and Week 20 | Intraretinal fluid and subretinal fluid are measured using OCT in the central subfield (center 1 millimetre \[mm\]). |
| Proportion of Participants With no Intraretinal Fluid and no subretinal fluid in the Study Eye at Weeks 40 or 44, or 48 | From Baseline and Week 40 or 44 or 48 | Intraretinal fluid and subretinal fluid are measured using OCT in the central subfield (center 1 mm). |
| Proportion of Participants With no Intraretinal Fluid and no subretinal fluid in the Study Eye at the end of the study | From Baseline and the end of the study (up to 104 weeks) | Intraretinal fluid and subretinal fluid are measured using OCT in the central subfield (center 1 mm). |
| Proportion of Participants With no Intraretinal Fluid, no Subretinal Fluid and no sub-RPE fluid in the Study Eye at Week 20 | From Baseline and Week 20 | Intraretinal fluid, subretinal fluid and sub-RPE fluid are measured using OCT in the central subfield (center 1 mm). |
| 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 | From Baseline and Week 40 or 44 or 48 | Intraretinal fluid, subretinal fluid and sub-RPE fluid are measured using OCT in the central subfield (center 1 mm). |
| 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 | From Baseline and the end of the study (up to 104 weeks) | Intraretinal fluid, subretinal fluid and sub-RPE fluid are measured using OCT in the central subfield (center 1 mm). |
| Change From Baseline in branch Neovascularization network in the Study Eye at 1 year | Baseline and 1 year | The branch neovascularization network in the study eye is evaluated by a central reading center using OCT angiography (OCTA). |
| Change From Baseline in branch Neovascularization network in the Study Eye at 2 years | Baseline and 2 years | The branch neovascularization network in the study eye is evaluated by a central reading center using OCT angiography (OCTA). |
| Proportion of participants on 12 weeks or more treatment intervals at the end of the study. | End of study (up to 100 weeks) | 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. |
| Number of faricimab injections received from Week 20 until the end of the study. | Week 20 through end of study (up to 100 weeks) | Count of the number of faricimab injections each participant received after the treatment initiation period (baseline to week 12). |
| Incidence and severity of ocular adverse events | From first dose of study drug through end of study (up to 104 weeks) | 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. |
| Incidence and severity of Non-Ocular Adverse Event | From first dose of study drug through end of study (up to 104 weeks) | 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. |
Countries
Italy, Portugal, Spain, United Kingdom
Contacts
CONTACTJoana F Tavares, PhD
CONTACTLiliana C Soares, MsC
Outcome results
None listed