Long Term Efficacy of Faricimab Using a Treat and Extend Regimen for Type 3 Macular Neovascularization
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Change in CST (central subfield thickness)
研究概览
简要总结
Type 3 macular neovascularization (MNV) is a subtype of neovascular age-related macular degeneration accounting for 10-20% of cases, notable for high rates of bilateral involvement and risk of profound vision loss, particularly if undertreated. Early and proactive therapy is crucial to prevent progression and preserve vision.
Faricimab offers potential advantages in this setting. Eyes with type 3 MNV often show thin choroid, reticular pseudodrusen, and high GA risk, reflecting compromised choroidal perfusion. While anti-vascular endothelial growth factor (VEGF) agents suppress neovascularization, prolonged VEGF blockade may impair choriocapillaris health. Ang-2 inhibition, by promoting Tie2 activation and vascular stability, may protect choriocapillaris and reduce widespread retinal edema and hemorrhages observed in type 3 MNV.
Finally, while treat-and-extend is widely used in practice, existing trials (TENAYA, LUCERNE) applied broader extension intervals than typically used clinically. In type 3 MNV, where undertreatment carries severe consequences, a more stringent faricimab-based treat-and-extend regimen with 2-week interval adjustments warrants investigation.
详细描述
1.1 The Nature of Type 3 macular neovascularization (MNV) and Recommended Therapeutic Approaches Type 3 MNV, also known as retinal angiomatous proliferation is a subtype of neovascular age-related macular degeneration (AMD) that is characterized by intraretinal neovascularization. The incidence of type 3 neovascularization is relatively lower than other subtypes of neovascular AMD, constituting 10 to 20% of entire neovascular AMD. However, it is a very important disorder because it often leads bilateral visual deterioration. The high risk of bilateral involvement is characteristic of type 3 neovascularization. In some cases, the visual prognosis of the initially uninvolved eye with better vision, is poorer than the initially involved eye. In addition, profound visual loss may occur during the treatment course, especially in undertreated cases.
Thus, preserving vision is particularly important in type 3 neovascularization, which subsequently highlights the importance of investigating more effective treatment strategies. We previously suggested the need for proactive treatment in type 3 neovascularization to reduce the risk of abrupt visual loss. Furthermore, due to the progressive nature of type 3 MNV, there is an increased risk of visual impairment as the stages advance. Therefore, it is imperative to administer aggressive treatment during the early phase of the disorder to impede the progression of disease stages.
1.2 Why is Faricimab Particularly Advantageous for Type 3 MNV? (My own hypothesis) 1.2.1 The potential of ang-2 inhibition in preserving choriocapillaris Eyes with type 3 MNV usually exhibits very thin choroid, a high prevalence of reticular pseudodrusen, and a lack of choroidal vascular hyperpermeability. These observations collectively indicate compromised choroidal perfusion in such eyes. In fact, the occurrence of geographic atrophy (GA) is particularly elevated in type 3 MNV, and it serves as a significant contributing factor to the progressive deterioration of visual acuity over the long term in this condition. Due to these factors, maintaining adequate choroidal perfusion becomes particularly crucial in the treatment of type 3 MNV.
The choriocapillaris is the most critical tissue for perfusion into the retinal pigment epithelium and retinal outer layers. While anti-vascular endothelial growth factor (VEGF) therapy is highly effective in stabilizing neovascularization, there have been concerns regarding its potential negative impact on the maintenance of retinal pigment epithelium and choriocapillaris by suppressing physiological VEGF, particularly following aflibercept therapy. In 2016, I was the first to propose the possibility that these aspects could pose a concern in the management of patients with type 3 MNV during actual clinical practice.
It has been demonstrated in animal models of choroidal neovascularization that tie2 activation has the potential to induce choriocapillaris regeneration. It is not yet certain whether such phenomena occur in humans. Nonetheless, these research findings can provide support for the hypothesis that tie2 activation through ang-2 inhibition could potentially confer benefits in cases of compromised choroidal perfusion, such as in type 3 MNV.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •[General]
- •Signed Informed Consent Form
- •Age > 50 years at the time of signing Informed Consent Form
- •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 (will be defined in details in protocol)
- •BCVA that is equal or higher than 24 Early Treatment Diabetic Retinopathy Study letters on Screening Day/ Day
- •Confirmed diagnosis, by the investigator, of symptomatic type 3 neovascularization based on sufficiently clear ocular media and adequate pupillary dilatation allowing acquisition of good quality retinal images for confirmation.
- •Treatment naive participants
排除标准
- •[General]
- •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 (which will be indicated in the Prohibited Therapy section in protocol)
- •Systemic treatment for suspected or active systemic infection on study Day 1
- •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 disease, metabolic dysfunction, physical examination finding, or historical or current clinical laboratory findings giving reasonable suspicion of a condition that contraindicates the use of the investigational drug or that might affect 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 anesthetic 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
- •Significant media opacities, including cataract, in the study eye that might interfere with visual acuity, assessment of safety, or fundus photography.
- •Any concurrent ocular condition in the study eye which, in the opinion of the investigator, could either increase the risk to the patient beyond what is to be expected from standard procedures of intraocular injection, or which otherwise may interfere with the injection procedure or with evaluation of efficacy or safety.
- •Any ocular or periocular infection within the last 2 weeks prior to Screening in either eye.
- •Any history of uveitis in either eye.
- •Presence of definite chorioretional anastomosis
- •Subretinal hemorrhage that is either 50% or more of the total lesion area, or if the blood is under the fovea and is 1 or more disc areas in size in the study eye. (If the blood is under the fovea, then the fovea must be surrounded 270 degrees by visible macular neovascularization.)
- •Scar or fibrosis, making up > 50% of total lesion in the study eye.
- •Scar, fibrosis, or atrophy involving the center of the fovea in the study eye.
- •Presence of retinal pigment epithelial tears or rips involving the macula in the study eye.
- •History or clinical evidence of diabetic retinopathy, diabetic macular edema or any other vascular disease affecting the retina, other than AMD, in either eye.
- •Any concurrent intraocular condition in the study eye (e.g. cataract) that, in the opinion of the investigator, could require either medical or surgical intervention during the 76 week study period.
- •Prior vitrectomy in the study eye
- •Any history of macular hole of stage 2 and above in the study eye.
- •Any intraocular or periocular surgery within 3 months of Day 1 on the study eye, except lid surgery, which may not have taken place within 1 month of day 1, as long as it's unlikely to interfere with the injection.
- •Prior trabeculectomy or other filtration surgery in the study eye.
- •Uncontrolled glaucoma (defined as intraocular pressure ≥ 25 mmHg despite treatment with antiglaucoma medication) in the study eye.
- •Active intraocular inflammation in either eye.
- •Active ocular or periocular infection in either eye.
- •Aphakia or pseudophakia with absence of posterior capsule (unless it occurred as a result of an yttrium aluminum garnet [YAG] posterior capsulotomy) in the study eye.
研究组 & 干预措施
Faricimab treatment arm
干预措施: Intravitreal faricimab injection (Drug)
结局指标
主要结局
Change in CST (central subfield thickness)
时间窗: Baseline to week 76
Change in central retinal thickness, as measured by optical coherence tomography, from baseline to week 76
次要结局
- Change in best-corrected visual acuity (BCVA)(Baseline to week 76)
- Choroidal thickness(Baseline to week 76)
- Geographic atrophy (GA) development(Baseline to week 76)
- Fluid resolution(Week 20, 52, and 76)
- Presence of neovascularization(Baseline, week 20, 52, and 76)
- Number of injection(Baseline to week 76)
- Maximum injection interval(Baseline to 76 weeks)
- Adverse event(Baseline to week 76)
研究者
Jae Hui Kim
Director of Clinical Research
Kim's Eye Hospital