A Randomized, Double-masked, Multicenter,Sham-controlled, Safety and Efficacy Study of KH902 in Patients With Wet AMD

Study Overview
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Brief Summary
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This study is designed to prove and confirm the efficacy and safety of multiple injections of human recombinant vascular endothelial growth factor receptor-Fc fusion protein (KH902) in patients with choroidal neovascularization due to neovascular age-related macular degeneration by comparing intravitreal injections of KH902 with sham-injections.

Detailed Description
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AMD is the leading cause of severe vision loss in people over the age of 65 in the United States and other western countries. A quantity of documents indicate that neovascularization promoted by VEGF is the main cause of visual acuity decline. Patients are starving for a new drug which can notably improve VA with less administration frequency and lower treatment cost. The new drug Recombinant Human VEGF Receptor-Fc Fusion Protein (KH902) is a gene fusion protein. The pre-clinical researches and phase II study showed that KH902 is well-tolerated,and safe, it is effective in inhibiting the growth, migration, pullulation of vascular endothelial cells and neovascularization induced by VEGF. This study is designed to prove and confirm the efficacy and safety of multiple injections of KH902 in patients with choroidal neovascularization due to neovascular age-related macular degeneration by comparing intravitreal injections of KH902 with sham-injections.

Official Title
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A Phase 3 Clinical Trial of Intravitreal Injections of Human Recombinant Vascular Endothelial Growth Factor Receptor-Fc Fusion Protein in Patients With Choroidal Neovascularization Secondary to Age-related Macular Degeneration

Conditions
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Neovascular Age-related Macular Degeneration

Intervention / Treatment
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* Biological: Recombinant Human VEGF Receptor-Fc Fusion Protein


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed the Informed Consent Form; Age ≥ 50 years of either gender; Total lesion size ≤ 30 mm2 of the study eye; BCVA score of the study eye between 73 and 19 letters; Clear ocular media and adequate pupil dilation to permit good quality fundus photographic imaging. BCVA score of the fellow eye ≥ 19 letters. Exclusion Criteria: Current or previous non-exudative AMD diseases which affect the inspection and measurement of macular or the central visual acuity; Subretinal hemorrhage area≥ 50% of total lesion size; Scar or fibrosis area in study eyes ≥ 50% of total lesion size; or central foveal scar、fibrosis or atrophy of macular in the study eye; Presence of retinal pigment epithelial tear, retinal macular tractional, macular epiretinal membrane, and diagnosed with polypoidal choroidal vasculopathy in the study eye; Previous anti-VEGF drug treatment in the study eye within six months preceding screening; or anti-VEGF treatment in the fellow eye within three months before screening; Previous intraocular or periocular operations, excluding operations on eyelid without hampering the intravitreal injection in the study eye; Previous ophthalmologic operations in the study eye; Current active inflammation or infection in either eye; Uncontrolled previous or current glaucoma in either eye, or previous glaucoma filtering operation in the study eye; Current systemic administrations which may lead to toxicity in the crystalline lens; History of allergy or current allergic response; History of surgery within one month preceding enrollment; Infectious diseases need systemic administration; Systemic autoimmune diseases; Any uncontrolled clinical disorders; Patients of child-bearing potential do not adopted adequate contraception methods; Pregnant or nursing women; Patients should be excluded in the opinion of investigators;

Ages Eligible for Study
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Minimum Age: 50 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: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 0.5 mg KH902<br>Patients will receive intravitreal injection of KH902 0.5mg/eye once per month for three times in the study eye, and then patients will receive 2 sham injections monthly, respectively, at the end of month 3 (visit 5), and following these injections you will receive intravitreal injection of KH902 once every three months, till month 12 (respectively at month 5, month 8 and month 11) | Biological: Recombinant Human VEGF Receptor-Fc Fusion Protein<br>* Intravitreal injection of KH902 once per month<br>|
| Sham Comparator: Sham-injection<br>Patients will receive sham injection once per month for three times, and then you will receive intravitreal injection of KH902 0.5mg/eye once per month for three times in the study eye, after three months' treatment they will receive intravitreal injection of KH902 once every three months, till month 12 (respectively at month 8 and month 11. | Biological: Recombinant Human VEGF Receptor-Fc Fusion Protein<br>* Intravitreal injection of KH902 once per month<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change from baseline in BCVA | To evaluate the mean change from baseline in best-corrected visual acuity (BCVA) in KH902 treatment group and sham treatment group at month 3 and compare the difference between the values | at month 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence rate of adverse event | To evaluate the difference in safety assessment between Conbercept (KH902) group and Sham group at month 3. | at month 3 | 
| Mean change of retinal thickness from baseline | To evaluate the mean change of retinal thickness from baseline in KH902 treatment group or sham treatment group at month 3. | at month 3 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Recombinant Human VEGF Receptor-Fc Fusion Protein (KH902), age-related macular degeneration (AMD), choroidal neovascularization (CNV), intravitreal injection, best corrected visual acuity (BCVA), central retinal thickness