Biomarkers, Effectiveness, and Safety of Aflibercept 8mg Modified Fixed Dose Regimen in Treatment-Naïve nAMD Patients

Официальное название

A Prospective, Multicenter, Open-Label Phase IV Clinical Study to Evaluate the Biomarkers, Effectiveness, and Safety Based On A Modified Fixed Dose Regimen of Aflibercept 8mg in Treatment-Naïve Patients With Neovascular Age-Related Macular Degeneration (nAMD)

Обзор

Primary objective: • To evaluate the change in aqueous humor vascular endothelial growth factor A (VEGF-A) levels after 2 months of initial treatment with 8 mg Aflibercept in treatment-naïve nAMD patients. Secondary objectives: • To assess the efficacy, safety, and biomarker changes of 8 mg Aflibercept using a modified fixed-interval dosing regimen over 12 months in treatment-naïve nAMD patients.

Подробное описание

Age-related macular degeneration (AMD) is a disease that affects the central part of the retina (the macula) and can lead to loss of central vision in older adults. In developed countries, this condition is the leading cause of central vision loss in this population. AMD has two clinical subtypes: dry and wet (neovascular) forms. The dry type is characterized by progressive accumulation of drusen, with secondary degeneration of the retinal pigment epithelium and photoreceptors; the wet type is characterized by retinal edema and neovascularization, which can lead to severe vision loss. Wet AMD is the main cause of most AMD-related blindness cases.

Inhibiting vascular endothelial growth factor (VEGF) activity with medication has been proven to be an effective therapeutic strategy for treating nAMD. In addition to Eylea® (Aflibercept) injection, multiple anti-VEGF drugs have been approved for nAMD treatment in various countries globally, such as Lucentis® (Ranibizumab), Conbercept, and Faricimab (Vabysmo®). Most nAMD patients require long-term chronic treatment. Although globally approved intravitreal (IVT) anti-VEGF therapies are effective and well tolerated, the need for frequent IVT injections (especially during the maintenance phase) places a significant burden on physicians, patients, and caregivers.

Currently, in China, local reimbursement policies for nAMD cover nine anti-VEGF injections, and patients must bear the cost for any additional treatments. As a chronic progressive disease, nAMD patients typically require longer-term management and more anti-VEGF therapies. Limitations in insurance reimbursement are a primary obstacle in clinical practice.

At the same time, anti-VEGF therapy requires a three-dose loading regimen (once per month), with frequent follow-up and a complex injection schedule, which imposes a significant financial burden on patients, increases treatment costs for physicians, results in low patient adherence, and ultimately reduces long-term visual benefits. A result from the Barometer global survey indicated that 95.2% of physicians and 83.9% of patients believe that improving the predictability of injection timing is the main direction for enhancing patient care.

Вмешательства

• Препарат Aflibercept 8mg
  All treatment-naïve nAMD patients who have completed screening and meet the eligibility criteria will be included in this study. Aflibercept 8 mg will be administered at Month 0, Month 2, Month 5, Month 8, and Month 11. A rescue treatment follow-up will be conducted at Month 1, and if the criteria for rescue treatment are met, one rescue treatment (Aflibercept 8 mg injection) will be given.

Первичные конечные точки

• VEGF-A levels in the patient's aqueous humor [Срок оценки: From enrollment to the end of treatment at 0 months、2months、5months、8months、11months]

Вторичные конечные точки (11)

• Proportion of patients who did not receive remedial treatment [Срок оценки: From enrollment to the end of treatment at 12 months]
• best corrected visual acuity (BCVA) [Срок оценки: From enrollment to the end of treatment at 12 months]
• central retinal thickness (CMT) [Срок оценки: From enrollment to the end of treatment at 12 months]
• VEGF-B levels in the patient's aqueous humor [Срок оценки: From enrollment to the end of treatment at 0 months、2months、5months、8months、11months]
• placental growth factor (PIGF) levels in the patient's aqueous humor [Срок оценки: From enrollment to the end of treatment at 0 months、2months、5months、8months、11months]
• Ang-2 levels in the patient's aqueous humor [Срок оценки: From enrollment to the end of treatment at 0 months、2months、5months、8months、11months]
• IL-6 levels in the patient's aqueous humor [Срок оценки: From enrollment to the end of treatment at 0 months、2months、5months、8months、11months]
• IL-8 levels in the patient's aqueous humor [Срок оценки: From enrollment to the end of treatment at 0 months、2months、5months、8months、11months]
• Average number of doses in the 12th month [Срок оценки: "From enrollment to the end of treatment at 12 months]
• the average area/volume of macular neovascularization (MNV) [Срок оценки: From enrollment to the end of treatment at 0 month、2months、5months、8months、11months]
• intraretinal fluid (IRF) or subretinal fluid (SRF) in the foveal area [Срок оценки: From enrollment to the end of treatment at 2months、12months]

Критерии участия

Критерии включения

• Patients who fully understand the content, procedures, and possible adverse events (AEs) of this study and are able to provide written informed consent;
• Male or female patients aged ≥50 years at the time of signing the informed consent;
• Women of childbearing potential (WOCBP) must agree to use dual contraception during the study and for 4 months after discontinuation of study treatment, consisting of one medically recognized contraceptive method with a failure rate of less than 1% per year (see Appendix 1 for Contraceptive Measures, Definitions and Requirements for Women of Childbearing Potential) combined with a barrier method (e.g., condom). Women who have undergone surgical sterilization (such as hysterectomy, bilateral oophorectomy, or bilateral tubal ligation) or menopause for more than 1 year are considered not of childbearing potential. Women of childbearing potential must have a negative pregnancy test at screening and must not become pregnant, breastfeed, lactate, or plan pregnancy, breastfeeding, or egg donation during the study and for 4 months after discontinuation of study treatment;
• Male subjects whose partners are of childbearing potential must agree to use dual contraception during the study and for 4 months after the end of treatment, consisting of one medically recognized contraceptive method with a failure rate of less than 1% per year (see Appendix 1 for Contraceptive Measures, Definitions and Requirements for Women of Childbearing Potential) combined with a barrier method (e.g., condom), and must agree not to donate sperm during the study and for 4 months after the end of treatment.

Inclusion Criteria for Study Eye

Subjects included in this study must meet all of the following ocular inclusion criteria for the study eye:

• Have sufficiently clear ocular media and adequately dilated pupils to obtain high-quality retinal images for diagnosis;
• Untreated nAMD with active subfoveal choroidal neovascularization (CNV), with total CNV area accounting for more than 50% of the total lesion area.
• SD-OCT examination showed the presence of intraretinal fluid (IRF) and/or subretinal fluid (SRF) in the foveal center of the retina.
• During the screening and baseline periods, BCVA scores measured using the ETDRS visual acuity chart at an initial testing distance of 4 meters ranged from 78 to 24 ETDRS letters (inclusive) (approximately equivalent to Snellen visual acuity 20/32 to 20/320), and the vision loss was caused by nAMD.

Критерии исключения

• Patients who have received other investigational treatments (including anti-VEGF, corticosteroids, laser photocoagulation treatments \[panretinal photocoagulation or macular photocoagulation\], and photodynamic therapy \[PDT\]) or approved nAMD drugs/therapies;
• Patients with allergies or hypersensitivity reactions to any component/excipient of the investigational product;
• Uncontrolled hypertension (defined as systolic blood pressure >160 mmHg or diastolic blood pressure >95 mmHg). Subjects may be treated with up to three known antihypertensive drugs to achieve adequate blood pressure control. This restriction applies to drugs that can be used for treating hypertension, even if the primary purpose of taking the drug for the subject is not blood pressure control. Any medication known to affect blood pressure must have a stable regimen for 12 weeks prior to screening;
• History of other diseases, metabolic dysfunctions, abnormal physical examinations, or clinical laboratory abnormalities that reasonably suggest a contraindication to the investigational drug, may interfere with the interpretation of study results, or could place the patient at high risk for treatment-related complications;
• Any condition that, in the opinion of the investigator, may affect the patient's ability to provide informed consent, comply with the study protocol, complete the study according to study procedures, or for which the patient's participation may affect the study results or their own safety; Exclusion criteria for study eye
• Any eye with diabetic retinopathy (DR), diabetic macular edema (DME), or any retinal vascular disease other than nAMD;
• Presence of extraocular/periocular infection or inflammation in any eye during the screening or baseline period;
• Presence of retinal pigment epithelium (RPE) tear or rupture, scarring, fibrosis, or atrophy involving the fovea;
• Fluorescein angiography (FA)/fundus photography (FP) showing:

• Total lesion area (including hemorrhage, scarring, and neovascularization) greater than 12 disc areas (30.5 mm²);
• Fibrosis or atrophy >50% of the total lesion area, and/or involving the fovea.
• Any intraocular disease that the investigator believes may reduce vision improvement or require medical or surgical intervention during the study (such as amblyopia, aphakia, retinal detachment, cataract, diabetic retinopathy or maculopathy, epiretinal membrane with traction):

• Presence of vitreous hemorrhage during the screening or baseline period;
• Uncontrolled glaucoma (intraocular pressure still >25 mmHg despite anti-glaucoma medication);
• Any cataract surgery or treatment for cataract surgery complications with steroids or yttrium-aluminum garnet (YAG) laser capsulotomy within 3 months prior to Day 1 of the study;
• Any prior intraocular surgery (e.g., vitrectomy, glaucoma surgery, corneal transplantation, or radiation therapy);
• Prior periocular or intravitreal drug injections (including anti-VEGF agents) for other retinal diseases;
• Presence of intraocular inflammation/infection in any eye within 12 weeks prior to the screening visit;
• History of idiopathic or autoimmune-related uveitis in the study eye.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07728981 · 2026KY-31

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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