Efficacy and Safety of Treat-and-Extend Regimen Versus Pro Re Nata of Conbercept in Age-related Macular Degeneration

Study Overview
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Brief Summary
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The study will evaluate the efficacy and safety of two different regimens of Conbercept (Treat-and-Extend (T&E) Regimen vs. Pro Re Nata (PRN)) in patients with wet AMD. This study is to provide long-term safety data in the treatment of patients with wet Age-related Macular Degeneration (AMD).

Detailed Description
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Participants with wAMD were randomized and received a T&E or PRN regimen for 24 months. Mean Snellen BCVA and mean central macular thickness by OCT were examined at each visit. Any treatment-related adverse events, such as endophthalmitis, and systemic adverse events, such as stroke, were evaluated during the research.

Official Title
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A Multicenter Study Comparing Efficacy and Safety of  Treat-and-Extend Regimen Versus Pro Re Nata Regimen of Conbercept in Neovascular Age-related Macular Degeneration

Conditions
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Age-related Macular Degeneration

Intervention / Treatment
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* Procedure: Treat-and-Extend regimen
* Procedure: Pro Re Nata
* Drug: Conbercept


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed-consent before any evaluation Visual impairment due to active CNV,including predominantly classic CNV,minimally classic CNV,occult CNV with no classic component and PCV. 50 years old and older Chinese For study eye: BCVA between 20/30 and 20/320 on electronic visual acuity texting at the time point of both screening and baseline. Exclusion Criteria: Have Stroke and myocardial infarction within 3 months before screening Any active periocular and ocular infection and inflammation (including blepharitis, conjunctivitis, keratitis, scleritis, uveitis, intraocular inflammation) while screening and baseline. Uncontrolled glaucoma (under treatment [IOP] ≥ 30 mm Hg or depend on researchers) while screening and baseline Neovascularization of iris and neovascular glaucoma while screening and baseline Any causes led to choroidal neovascularization except Wet AMD (including ICNV,central serous chorioretinopathy,ocular histoplazmoza and pathologic myopia) while screening and baseline With structure injury (including vitreous macular traction,epiretinal membrane involving in central fovea,subretinal fibroplasia,laser scar and central fovea atrophy) within 0.5 optic disc diameter to the central of macula while screening and baseline, which may harm the improvement of vision by treatment according to researchers Any systemic anti-VEGF medication(as Avastin) use within 3 months before screening Any medication systemic use toxic to lens, retina and optic nerve,including iron amine, chloroquine/chloroquine (Plaquenil ®), tamoxifen, phenothiazine and ethambutol For study eye：Used to accept following treatments for wet AMD within 3 months or accept following treatments more than three times before baseline: a)Anti-angiogenesis drugs(pegaptanib （Macugen®），ranibizumab ,bevacizumab（Avastin®),VEGF-Trap，KH902；b）Anecortave acetate corticosteroids；c）Protein kinase C inhibitors，squalamine，siRNA; d)PDT （Visudyne®）treatment,external beam radiotherapy, local laser photocoagulation, vitrectomy, submacular surgery and transpupillary thermotherapy Any intraocular surgery(including YAG laser) within 3 months before baseline or predicated within 6 months after baseline Intraocular or periocular treatment of corticosteroids within 3 months before baseline For follow eye:Any anti-angiogenesis treatment(including anti-VEGF,like Lucentis,Avastin® and KH902 ) within 3 months before baseline

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Conbercept 0.5mg Treat-and-Extend regimen<br>Monthly intravitreal injections of Conbercept 0.5mg in the core treatment period and Treat-and-Extend Regimen of the same dose guided by BCVA stabilization and optical coherence tomography (OCT) in the extension treatment period. Intervention: Drug: Conbercept | Procedure: Treat-and-Extend regimen<br>* For the T&E regimen,investigators recorded patients' data after retreatment by 3 monthly intravitreal injections of Conbercept. Patients were examined 6 weeks after the third injection, with ETDRS visual acuity testing, fundus ophthalmoscopy and photography, and OCT, and treated on the same day. The interval between treatments was extended by 2-week (12-week was a maximum) provided that OCT and fundus examination did not show either exudative manifestations or new macular hemorrhage or active CNV or reduced by 2 weeks (4-week was minimum) in case of such manifestations or hemorrhage. The persistence of pigment epithelium detachment was not considered a condition that justified shortening the interval between injections.<br>* Other names: T&E;Drug: Conbercept<br> <br> |
| Active Comparator: Conbercept 0.5mg Pro Re Nata<br>Monthly intravitreal injections of Conbercept 0.5mg in the core treatment period and PRN intravitreal injections of the same dose guided by BCVA stabilization in the extension treatment period. Intervention: Drug: Conbercept | Procedure: Pro Re Nata<br>* For the PRN group, investigators recorded patients'data after retreatment by 3 monthly intravitreal injections of Conbercept.Subsequent reinjections were given as needed according to the changes in patients'visual acuity and/or the exudation shown by OCT. Four to five weeks after the third and last injection, all patients in the PRN group underwent an examination, including ETDRS visual acuity, fundus photography,and OCT. In case of persistent subfoveal or perifoveal fluid, macular intraretinal edema, visual loss of >5 letters, or the occurrence of a new hemorrhage, patients were retreated. The persistence of hemorrhage without evidence of fluid was not considered a criterion for retreatment. In the absence of retreatment criteria, no further injections were given and another examination was proposed usually 4 weeks later.<br>* Other names: PRN;Drug: Conbercept<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Snellen BCVA at every visit or treatment | Compare of mean Snellen Best-Corrected-visual-acuity at every visit or treatment between the two groups to assess the efficacy of Treat-and-Extend regimen of Conbercept. | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-related adverse events | Compare of Number of participants with treatment-related adverse events between the two groups to assess the safety of Treat-and-Extend regimen of Conbercept | 24 months | 
| Mean number of injections after the initial three loading dose monthly injections | Compare of mean number of injections after the initial three loading dose monthly injections between the two groups to assess the efficacy of Treat-and-Extend regimen of Conbercept. | 21 months | 
| mean central macular thickness at every visit or treatment by OCT | Compare of mean central macular thickness by OCT at every visit or treatment between the two groups to assess the efficacy of Treat-and-Extend regimen of Conbercept. | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Age-related Macular Degeneration, Conbercept, Treat-and-Extend Regimen, Pro Re Nata