Neovascular Age-related Macular Degeneration
Conditions
Interventions
Phase 1 SAD group:5 dose groups climbing in a 3+3 traditional manner with a single dose, with sequential entry from low to high dose.
Phase 1 MAD group:Based on the results of the SAD component, two safe and initially effective doses were selected for the MAD study, administered once every 4 weeks and repeated 4 times.
Phase 2 control group:12-week treatment period with dosing every 4 weeks.
Phase 2 trial low-dose group:Low dose, 12 week treatment period, administered every 4 weeks.
Phase 2 trial high-dose group:High dose, 12 week treatment period, administered every 4 weeks.
Sponsors
Tianjin Medical University Eye Hospital
Eligibility
Sex/Gender
All
Age
50 Years to No maximum
Inclusion criteria
Inclusion criteria: Subjects must meet all of the following inclusion criteria to be enrolled in this study. Inclusion criteria for study eyes: 1) Patients with nAMD who have a confirmed diagnosis of choroidal neovascularization (CNV) secondary to AMD. 2) Subcentral recess CNV as determined by FFA or ICGA, or combined paracentral/extracentral recess CNV with subcentral recess CNV activity (CNV activity defined as the presence of subretinal fluid, subretinal hyperreflective material, leakage, or evidence of hemorrhage). 3) All types of CNV damage (i.e., CNV lesion types in the study eye including typical predominant, mildly typical, or occult [including polypoid choroidal vasculopathy (PCV)]) that meet the following 4 conditions: a) FFA findings of damaged area (including hemorrhage/hemorrhage, atrophy, fibrosis, neovascularization) = 9 optic discs; b) Overall CNV damage visible on the FFA representing 50% or more of the total damaged area of 50% or more; c) FFA confirmed the presence of active CNV (evidence of leakage); d) SD-OCT confirmed the presence of CNV leakage (presence of effusion). 4) Best corrected visual acuity (BCVA) of 78 - 24 letters (equivalent to 20/32 - 20/320 as assessed by the Snellen method) as assessed by the ETDRS visual acuity chart at enrollment. Note: Only 1 eye was assigned as the study eye, and if both eyes met the inclusion criteria, the eye with the worse baseline BCVA was selected, unless the other eye was deemed more appropriate by the investigator. 5) No prior IVT anti-VEGF therapy (i.e., primary patients) or prior IVT anti-VEGF therapy, with the last IVT injection occurring at least 3 months from Day 1 (Day 1) of the study and prior IVT anti-VEGF therapy judged effective by the investigator (i.e., treated patients). 6) Absence of refractive media clouding and pupillary constriction that would interfere with fundus examination. General inclusion criteria: 7) Ability to provide signed written informed consent. 8) Ability to comply with the treatment and follow-up requirements of the study protocol, as judged by the investigator. 9) Be = 50 years of age at the time of screening, with no restriction on gender. 10) Agree not to participate in any other clinical studies, including clinical studies of other investigational new drugs or devices, until this study is completed. 11) Females of childbearing potential are required to have a negative urine pregnancy test result during the screening period and agree to use an acceptable or less than 1% annual failure rate of contraceptive methods, including hormonal methods (oral contraceptives, patch contraceptives or medroxyprogesterone acetate), or intrauterine devices, implantable progestational contraceptives that suppress ovulation, bilateral tubal ligations, for the entire study period up to at least 3 months after the last dose, male sterilization. In the judgment of the investigators, abstinence was considered an acceptable method of contraception. Fertility was defined as: female subjects were considered fertile if they were menopausal but had not reached postmenopausal status (i.e., had not reached: menopause for a period of time greater than or equal to 12 consecutive months for no reason other than menopause) and had not undergone sterilization (removal of both ovaries and/or uterus and/or both fallopian tubes). Unacceptable contraceptive methods: The reliability of the subject's contraceptive preference was evaluated in relation to abstinence relate
Exclusion criteria
Exclusion criteria: Those meeting any of the following criteria will be excluded. Exclusion criteria for study eyes: 1) CNV due to a cause other than AMD, e.g., due to diabetic macular edema (DME), retinal vein occlusion (RVO), ocular histoplasmosis, trauma, pathological myopia, vascular-like streaks, choroidal rupture, or uveitis. 2) Any macular lesion not related to AMD that affects vision or causes intraretinal or subretinal fluid accumulation. 3) The presence of permanent structural damage in the central macular sulcus. 4) At the time of the FFA examination, there is visible: (i) subretinal hemorrhage exceeding 50% of the total lesion area and/or involvement of the central recess; (ii) fibrosis or atrophy exceeding 50% of the total lesion area and/or involvement of the central recess. 5) Presence of any comorbid ocular disease (e.g., central plagiochoroidal retinopathy, retinal pigment epithelial tear involving the macula, amblyopia, aphakia, retinal detachment, cataract, diabetic retinopathy or macular degeneration, anterior retinal traction) that in the opinion of the investigator may affect visual acuity improvement or require medical intervention during the study period. 6) Refractive error of more than 8 diopters confirmed by spherical equivalent (SER) after optometry (without dilated pupils); for patients with previous refractive surgery or cataract surgery, preoperative refractive error confirmed to be more than 8 myopic diopters. In the absence of an assessable refractive value, an eye axis > 26.5 mm should be excluded. 7) Presence of uncontrolled glaucoma (e.g., progressive visual field loss, or defined as intraocular pressure (IOP) = 25 mmHg despite standard antiglaucoma treatment). 8) Presence of vitreous hemorrhage (to a degree of trace or greater, see protocol appendix 1) prior to study day 1 (Day 1) dosing. 9) Any prior or combined medication/treatment for CNV or vitreous macular interface abnormalities within 3 months prior to study day 1 (Day 1), including but not limited to IVT implantation or injection therapy (e.g., steroids, tissue fibrinogen activator, oxyfibrin, C3F8 filling, air filling. see entry criteria #5 for IVT anti-VEGF therapy), periocular pharmacologic intervention , argon laser photocoagulation, vetiporfin photodynamic therapy, secondary tube laser, transpupillary thermotherapy, or surgical intervention. 10) Have undergone any cataract surgery, or treatment of cataract surgery complications with steroids, or YAG (yttrium aluminum garnet) laser posterior capsulotomy within 3 months prior to study day 1 (Day 1). 11) Have undergone any other previous intraocular surgery (e.g., ciliary flatus vitrectomy, glaucoma surgery, corneal transplantation, or radiation therapy) 12) Received periocular pharmacological intervention or IVT for other retinal disease within 6 months prior to the screening visit. Contralateral eye exclusion criteria: 13) BCVA < 24 letters in the contralateral eye (non-study eye) during the screening period and on Day 1 (Day 1) of the study. 14) No non-study eye (i.e., monocular) during the screening period and Day 1 of the study (Day 1). Bilateral exclusion criteria: 15) Either eye has received a previous Y400 IVT injection. 16) History of idiopathic or autoimmune associated uveitis in either eye. 17) Active ocular inflammation or suspected active ocular or periocular infection prior to study day 1 (Day 1) dosing. General exclusion criteria: 18) Known allergy to sodi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence and severity of ocular local adverse events, including dose-limiting toxicity events; | — |
Secondary
| Measure | Time frame |
|---|---|
| Changes in BCVA and CST over time from baseline;Safety and tolerability; | — |
Countries
China
Contacts
Public ContactLi Xiao Rong
Tianjin Medical University Eye Hospital
Outcome results
None listed