Neovascular Age-related Macular Degeneration
Conditions
Brief summary
The purpose of this clinical study is to evaluate the efficacy and safety of two different levels of conbercept intravitreal (IVT) injection as compared to the approved vascular endothelial growth factor (VEGF) antagonist active control, aflibercept intravitreal injection (2.0 mg/eye, Eylea®), in subjects with neovascular AMD.
Detailed description
A multicenter, multinational, double-masked, parallel-group, dose-ranging, active-controlled, randomized trial, which will randomize approximately 1140 subjects in a ratio of 1:1:1 to receive IVT injections of 0.5 mg conbercept, 1.0 mg conbercept, or 2.0 mg aflibercept. The trial includes a screening period of less than or equal to 14 days, followed by a treatment period of 92 weeks (last assessment at 96 weeks) with primary efficacy analysis at 36 weeks.
Interventions
BIOLOGICAL0.5 mg Conbercept Intravitreal Injection
Subjects received 0.5 mg conbercept intravitreal injection at Day 1, Week 4 and Week 8 (three injection loading dose), and treated every eight weeks thereafter (0.5 mg, q8w) for a total of 92 weeks treatment in the study eye.
BIOLOGICAL1.0 mg Conbercept Intravitreal Injection
Subjects received 1.0 mg conbercept intravitreal injection at Day 1, Week 4 and Week 8 (three injection loading dose), and treated every twelve weeks thereafter (1.0 mg, q12w) for a total of 92 weeks treatment in the study eye.
Subjects received 2.0 mg aflibercept intravitreal injection at Day 1, Week 4 and Week 8 (three injection loading dose), and treated every eight weeks thereafter (2.0 mg, q8w) for a total of 92 weeks of treatment in the study eye.
Sponsors
Chengdu Kanghong Biotech Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Men and women ≥ 50 years of age at the Screening visit; 2. Females must be at least 1 year postmenopausal, or surgically sterilized, or, if of childbearing potential, must have a negative pregnancy test at the Screening visit; o Women of childbearing potential must agree to use a highly effective method of contraception throughout the study. 3. Have received no previous treatment for neovascular AMD, including laser photocoagulation and/or photodynamic therapy (PDT) and/or IVT VEGF antagonists (treatment naïve) and; 4. Have active subfoveal choroidal neovascularization (CNV) lesions secondary to AMD (including polypoidal choroidal vasculopathy (PCV)) evidenced by subfoveal fluorescein angiography (FA) leakage, or definite subfoveal fluid by SD-OCT in the study eye at Screening; 5. Have a ETDRS BCVA letter score of 78 to 25 in the study eye at Screening; 6. Are willing and able to sign the study written informed consent form (ICF).
Exclusion criteria
1. Have had any prior ocular or systemic treatment (investigational or approved) or surgery for the treatment of neovascular AMD in the study eye except dietary supplements or vitamins; 2. Have participated as a subject in any interventional clinical trial within one month (30 days) prior to Baseline visit; 3. Have a subretinal hemorrhage that is either 50% or more of the total lesion area, or blood is under the fovea and is one or more disc areas in size (greater than 2.5 mm2) in the study eye at Screening; 4. Have any retinal pigment epithelial tears or rips in the study eye at Screening or upon examination at Baseline; 5. Have any vitreous hemorrhage in the study eye upon examination at Baseline or history of vitreous hemorrhage within eight weeks prior to Screening; 6. Have any other cause of CNV; 7. Have had prior pars plana vitrectomy in the study eye; 8. Have presence of a full thickness macular hole at Screening or upon examination at Baseline or a history of a full thickness macular hole in the study eye; 9. Have prior trabeculectomy or other filtration surgery in the study eye; 10. Have uncontrolled glaucoma; 11. Have active intraocular inflammation in either eye at Screening or upon examination at Baseline or a history of uveitis in either eye; 12. Have aphakia or pseudophakia with absence of posterior capsule (unless it occurred as a result of yttrium aluminum garnet (YAG) posterior capsulotomy) in the study eye; 13. Significant media opacities, including cataract, in the study eye that, in the opinion of the Investigator, could require either medical or surgical intervention during the study period; 14. Have any use of long acting intraocular steroids, including implants, within six months prior to Day 1, Baseline; 15. Have any known allergy to povidone iodine or known serious allergy to the fluorescein sodium for injection in angiography; 16. Any history of known contraindications indicated in the Food and Drug Administration (FDA)-approved label for the active control; 17. If female, be pregnant (positive urine pregnancy test at Screening) or breastfeeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean change from baseline in best corrected visual acuity (BCVA) at Week 36 in the study eye | Baseline to Week 36 | BCVA was assessed by Early Treatment of Diabetic Retinopathy Study (ETDRS) method |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of subjects gaining ≥15 ETDRS BCVA letters from baseline to Week 36 | Baseline to Week 36 | To assess proportion of subjects gaining ≥15 ETDRS BCVA letters from baseline to Week 36 |
| Mean change from baseline in central retinal thickness (µm) by spectral domain optical coherence tomography (SD-OCT) at Week 36 | Baseline and Week 36 | To assess mean change from baseline in central retinal thickness (µm) by spectral |
| Proportion of subjects maintaining vision (i.e. losing <15 ETDRS BCVA letters) from baseline to Week 48 | Baseline to Week 48 | To assess proportion of subjects maintaining vision (i.e. losing \<15 ETDRS BCVA letters) from baseline to Week 48 |
| Mean change from baseline in ETDRS BCVA letter score at Week 96 | Baseline and Week 96 | To assess mean change from baseline in ETDRS BCVA letter score at Week 96 |
| Proportion of subjects maintaining vision (i.e., losing <15 ETDRS BCVA letters) from baseline to Week 36 | Baseline to Week 36 | To assess proportion of subjects maintaining vision (i.e., losing \<15 ETDRS BCVA letters) from baseline to Week 36 |
| Blood concentration of conbercept doses conducted in a subgroup of subjects, when feasible | Baseline to Week 96 | To assess the blood concentration of conbercept doses conducted in a subgroup of subjects, when feasible |
| Half-life (t1/2) of conbercept doses conducted in a subgroup of subjects, when feasible | Baseline to Week 96 | To assess half-life (t1/2) of conbercept doses conducted in a subgroup of subjects, when feasible |
| Presence of anti-drug antibody of conbercept doses conducted in a subgroup of subjects, when feasible | Baseline to Week 96 | To assess the presence of anti-drug antibody of conbercept doses conducted in a subgroup of subjects, when feasible |
| Number of participants with adverse events as measure of safety and tolerability | Baseline to Week 96 | To assess the number of participants with adverse events as measure of safety and tolerability |
Countries
Argentina, Australia, Austria, Belgium, Canada, Chile, Colombia, Germany, Hong Kong, Lithuania, Mexico, Netherlands, New Zealand, Peru, Philippines, Poland, Portugal, Singapore, Spain, Switzerland, Taiwan, United States
Outcome results
None listed