The Study of Drug SCT510A in Patients With Wet Age-related Macular Degeneration (wAMD)

Study Overview
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Brief Summary
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Multicenter ，open-label, multi-dose study to evaluate the safety and tolerability in patients with wAMD treated with intravitreal recombinant humanized anti-VEGF monoclonal antibody（SCT510A）

Official Title
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A Multicenter, Open-label, Multi-dose, Phase I / II Clinical Study to Evaluate Safety, Tolerability, Pharmacokinetics, Efficacy and Pharmacodynamic Characteristics of SCT510A in the Patients With Wet Age-related Macular Degeneration.

Conditions
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Wet Age-related Macular Degeneration

Intervention / Treatment
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* Drug: SCT510A


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent form; Age≥45 years，≤80 years，male or femal; The study eye must meet the following criteria： Diagnosis of wAMD； Primary or recurrent active subfoveal or parafoveal choroidal neovascularization (CNV) lesions secondary to AMD； Total area of all types of lesions ≤12 optic disc areas（30mm2）； Best-corrected visual acuity of the study eye 70 letters or worse(Snellen equivalent of 20/40 or worse)； No optometric media opacity and pupil shrinkage. Best-corrected visual acuity of the fellow eye 19 letters or better（Snellen equivalent of 20/400 or better）. Exclusion Criteria: The study eye suffers structural damage of retinal which involves fovea，and the investigator assess that there is a risk of retinal detachment； Significant afferent pupillary defect (APD) in the study eye； The study eye has no lens( except intraocular lens) or posterior capsular rupture of the lens； In addition to AMD，there are other obvious eye diseases/conditions，such as pseudoexfoliation syndrome，rhegmatogenous retinal detachment，macular hole，diabetic retinopathy and diabetic macular disease which need to be treated； CNV caused by other causes other than wAMD, such as vascular stripe disease, ocular histoplasmosis, case myopia, trauma, etc； Uncontrolled glaucoma in the study eye (defined as IOP≥25mmHg after antiglaucoma treatment),or recevied glaucoma filtering surgery； History of vitreous hemorrhage in the study eye within 2 months before the first administration； Active inflammation or infection in either eye, such as conjunctivitis,keratitis, scleritis, endophthalmitis, or uveitis，ect； Previous intraocular surgery ，or laser therapy for wAMD(as photodynamic therapy,transpupillary thermotherapy,etc.) in the study eye within 3 months before the first administration； Previous intraocular or periocular injection of anti-VEGF or corticosteroid drugs (such as ranibizumab, bevacizumab, conbercept, aflibercept, brolucizumab, pegaptanib sodium, anecortave acetate, triamcinolone acetonide, etc.) in either eye within 3 months before the first administration； History of allergy to fluorescein sodium or indocyanine green； PLT≤100×109/L；thrombin time and prothrombin time exceed the upper limit of normal range (based on the laboratory normal value of clinical trial institution), and the abnormality is clinically significant according to the evaluation of the investigators； Abnormal liver and kidney function； Uncontrolled blood pressure control，systolic blood pressure≥160mmhg ,or diastolic blood pressure≥100mmhg； History of surgery within one month before the first administration, or current non-healing wound, ulcer, or fracture，etc； Patients with any of the following serious systemic diseases，such as serious mental, neurological, cardiovascular, respiratory and other system diseases and malignant tumors, systemic immune system diseases, diabetes mellitus with uncontrolled blood sugar(HbA1c>10%), disseminated intravascular coagulation and significant bleeding tendency； Suffering from systemic infectious diseases requiring oral, intramuscular or intravenous administration； Pregnant, lactating women and the patients who can not take contraceptive measures.

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SCT510A dose level 1 treatment<br>SCT510A(0.625mg), Vitreous injection, injection once every 4 weeks，three times continuously | Drug: SCT510A<br>* SCT510A of 0.625mg、1.25mg、2.0mg、2.5mg,IVT<br>|
| Experimental: SCT510A dose level 2 treatment<br>SCT510A(1.25mg), Vitreous injection, injection once every 4 weeks，three times continuously | Drug: SCT510A<br>* SCT510A of 0.625mg、1.25mg、2.0mg、2.5mg,IVT<br>|
| Experimental: SCT510A dose level 3 treatment<br>SCT510A(2.0mg), Vitreous injection, injection once every 4 weeks，three times continuously | Drug: SCT510A<br>* SCT510A of 0.625mg、1.25mg、2.0mg、2.5mg,IVT<br>|
| Experimental: SCT510A dose level 4 treatment<br>SCT510A(2.5mg), Vitreous injection, injection once every 4 weeks，three times continuously | Drug: SCT510A<br>* SCT510A of 0.625mg、1.25mg、2.0mg、2.5mg,IVT<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-Limiting toxicity(DLT) | Incidence of dose-limiting toxicities up to the Day 14 visit | From Day 0 up to Day 14 | 
| Maximum tolerated dose(MTD） | Maximum tolerated dose | From Day 0 up to Day 140 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK profile | Change of SCT510A drug concentration in the blood with time | From Day 0 up to 84 days | 
| Cmax | The maximum blood concentration after SCT510A drug enters the bloodstream | From Day 0 up to 84 days | 
| Tmax | Time to the Maximum Concentration of SCT510A | From Day 0 up to 84 days | 
| t1/2 | Elimination Phase Half-life of SVT510A | From Day 0 up to 84 days | 
| Biomarker | Detection of free VEGF concentration | From Day 0 up to 84 days | 
| Immunogenicity | Positive rate of ADA and NAb | From Day 0 up to 112 days | 
| central retina thickness（CRT） | Changes in CRT compared to the baseline | From Day 0 up to 140 days | 
| Macular edema volume | Changes in Macular edema volume compared to the baseline | From Day 0 up to 140 days | 
| Best corrected visual acuity（BCVA） | Changes in BCVA compared to the baseline | From Day 0 up to 140 days |