Neovascular Age-Related Macular Degeneration (nAMD) Wet AMD
Conditions
Keywords
Neovascular Age-Related Macular Degeneration, Aflibercept 8mg, Modified Fixed Dose Regimen
Brief summary
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.
Detailed description
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.
Interventions
DRUGAflibercept 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.
Sponsors
Tianjin Medical University Eye Hospital
Hebei General Hospital
Shijiazhuang People's Hospital
The Affiliated Hospital of Inner Mongolia Medical University
Shanxi Eye Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
50 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1. Patients who fully understand the content, procedures, and possible adverse events (AEs) of this study and are able to provide written informed consent; 2. Male or female patients aged ≥50 years at the time of signing the informed consent; 3. 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; 4. 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: 5. Have sufficiently clear ocular media and adequately dilated pupils to obtain high-quality retinal images for diagnosis; 6. Untreated nAMD with active subfoveal choroidal neovascularization (CNV), with total CNV area accounting for more than 50% of the total lesion area. 7. SD-OCT examination showed the presence of intraretinal fluid (IRF) and/or subretinal fluid (SRF) in the foveal center of the retina. 8. 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.
Exclusion criteria
1. 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; 2. Patients with allergies or hypersensitivity reactions to any component/excipient of the investigational product; 3. 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; 4. 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; 5. 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;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| VEGF-A levels in the patient's aqueous humor | From enrollment to the end of treatment at 0 months、2months、5months、8months、11months | In the second month, the average change in VEGF-A levels in the patient's aqueous humor relative to baseline |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of patients who did not receive remedial treatment | From enrollment to the end of treatment at 12 months | Proportion of patients who did not receive remedial treatment within 12 months |
| best corrected visual acuity (BCVA) | From enrollment to the end of treatment at 12 months | At month 12, the changes in the patient's best corrected visual acuity (BCVA) relative to baseline |
| central retinal thickness (CMT) | From enrollment to the end of treatment at 12 months | At month 12, the changes in the patient's central retinal thickness (CMT) relative to baseline |
| VEGF-B levels in the patient's aqueous humor | From enrollment to the end of treatment at 0 months、2months、5months、8months、11months | In the second month, the average change in VEGF-B levels in the patient's aqueous humor relative to baseline |
| placental growth factor (PIGF) levels in the patient's aqueous humor | From enrollment to the end of treatment at 0 months、2months、5months、8months、11months | In the second month, the average change in placental growth factor (PIGF) levels in the patient's aqueous humor relative to baseline |
| Ang-2 levels in the patient's aqueous humor | From enrollment to the end of treatment at 0 months、2months、5months、8months、11months | In the second month, the average change in Ang-2 levels in the patient's aqueous humor relative to baseline |
| IL-6 levels in the patient's aqueous humor | From enrollment to the end of treatment at 0 months、2months、5months、8months、11months | In the second month, the average change in IL-6 levels in the patient's aqueous humor relative to baseline |
| IL-8 levels in the patient's aqueous humor | From enrollment to the end of treatment at 0 months、2months、5months、8months、11months | In the second month, the average change in IL-8 levels in the patient's aqueous humor relative to baseline |
| Average number of doses in the 12th month | "From enrollment to the end of treatment at 12 months | Average number of doses in the 12th month |
| the average area/volume of macular neovascularization (MNV) | From enrollment to the end of treatment at 0 month、2months、5months、8months、11months | At each key visit time point, the relative change from baseline in the average area/volume of macular neovascularization (MNV) in patients ... |
| intraretinal fluid (IRF) or subretinal fluid (SRF) in the foveal area | From enrollment to the end of treatment at 2months、12months | Percentage of patients with no intraretinal fluid (IRF) or subretinal fluid (SRF) in the foveal area at months 0, 2, and 12 |
Contacts
CONTACTXinjun Ren, PHD
CONTACTShoukuan Liu, master
Outcome results
None listed