Initial Versus Delayed PDT Combination With Conbercept in PCV

Study Overview
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Brief Summary
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To compare the initial versus delayed verteporfin photodynamic therapy (PDT) in combination with conbercept in patients with symptomatic polypoidal choroidal vasculopathy (PCV).

Detailed Description
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Polypoidal choroidal vasculopathy (PCV) is characterized by polypoidal choroidal vascular dilatation with or without abnormally branching vascular networks(BVN) on indocyanine green angiography (ICGA). It has been considered to be a subtype of wet age-related macular degeneration(wAMD). PCV is more prevalent in Asian patients than in white patients; nearly half of Chinese patients who was diagnosed with wAMD actually was PCV. However, recently, the first choice treatment for wAMD has shifted to anti-vascular endothelial growth factor (VEGF) drugs, such as bevacizumab(Avastin,Genentech Inc), ranibizumab (Lucentis, Genentech Inc)and aflibercept (Eylea, Regeneron,Berlin,Germany) from PDT, and the vision improving effect has been confirmed regardless of race or disease subtype. Therefore, eyes with PCV can be treated initially with anti-VEGF drugs, however, they are limited in their ability to resolve polypoidal lesions, for which PDT works effectively. Combination therapy of PDT and anti-VEGF drugs provides the complementary effects of both treatments, but it remains unknown whether PDT should have been administered at the beginning of treatment or during follow-up of anti-VEGF therapy. The purpose of this study was to compare the 12-months treatment results of initial and delayed PDT combined with conbercept (Lumitin, Chengdu Kang Hong Biotech Co., Ltd., Sichuan, China) for PCV.

Official Title
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Efficacy and Safety of Initial Versus Delayed Verteporfin Photodynamic Therapy in Combination With Conbercept in Patients With Symptomatic Polypoidal Choroidal Vasculopathy

Conditions
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Polypoidal Choroidal Vasculopathy

Intervention / Treatment
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* Drug: conbercept
* Procedure: Initial PDT
* Procedure: Delayed PDT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Either gender，age ≥ 40. BCVA at study entry of 34 to 79 letters (Snellen Equivalent 20/200 to 20/25). Naive symptomatic PCV patients. Presence of PCV assessed based on ICG with active polyps with or without abnormal vascular network. No refractive media opacity or small pupil narrow that influence the fundus examination. Women must be using effective contraception, be post-menopausal for at least months prior to trial entry, or surgically sterile. Ability to provide written informed consent and to return for all study visits. Exclusion Criteria: Active inflammation or infection in the study eye. Uncontrolled intraocular pressure (>25 mmHg) in the study eye. Ocular condition in the study eye which may impact vision and confound study outcomes (e.g. vitreomacular traction, epiretinal membrane with BCVA impact, ocular inflammation, retinal vascular diseases like diabetic retinopathy or diabetic macular edema). Presence of centro macular scarring or atrophy indicating irreversible BCVA loss. Prior treatment of the study eye with anti-VEGF therapy or systemic use of anti-VEGF products within 3 months prior to the study entry. Previous vitrectomy, macular laser treatment, PDT, or intraocular steroids in the study eye. Allergy to fluorescein, ICG, iodine, shellfish. Pregnant or breast-feeding women.

Ages Eligible for Study
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Minimum Age: 40 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: Initial PDT combination with Conbercept<br>Conbercept 0.5 mg(0.05ml): Administered at baseline, and then PRN based on retreatment criteria monthly from month 1 to 11. PDT: PDT with verteporfin is administered at baseline and then PRN PDT combination with conbercept injection based on retreatment criteria from month 3 to 11. PDT treatment must be administered within 7 days after the injection. If same day treatment of conbercept and PDT is performed, conbercept injection is to be administered at least 2 hours after the PDT. PDT should cover the whole area of polyps and branch vascular net (BVN).The PRN PDT retreatment intervals should be no less than 3 months. | Drug: conbercept<br>* At baseline conbercept injection is administered.And thereafter is administered based on re-treatment criteria from month 1 to 11.The PRN conbercept re-injection should be monthly.<br>* Other names: lumitin;Procedure: Initial PDT<br>* At baseline PDT with verteporfin is administered initially.And thereafter PDT is administered based on re-treatment criteria from month 3 to 11.The PRN PDT retreatment intervals should be no less than 3 months.<br>* Other names: verteporfin;|
| Active Comparator: Delayed PDT combination with Conbercept<br>Conbercept 0.5 mg(0.05ml): Administered at baseline, and then PRN based on retreatment criteria monthly from month 1 to 11. PDT:PRN PDT combination with conbercept injection based on retreatment criteria from month 3 to 11. PDT treatment must be administered within 7 days after the injection. If same day treatment of conbercept and PDT is performed, conbercept injection is to be administered at least 2 hours after the PDT. PDT should cover the whole area of polyps and branch vascular net (BVN).The PRN PDT retreatment intervals should be no less than 3 months. | Drug: conbercept<br>* At baseline conbercept injection is administered.And thereafter is administered based on re-treatment criteria from month 1 to 11.The PRN conbercept re-injection should be monthly.<br>* Other names: lumitin;Procedure: Delayed PDT<br>* PDT is administered based on re-treatment criteria from month 3 to 11.The PRN PDT retreatment intervals should be no less than 3 months.<br>* Other names: verteporfin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Best Corrected Visual Acuity (BCVA) in each group,Compare the difference between the two groups. |  | from baseline (month 0) to month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of polyps regression assessed by ICGA in each group.Compare the difference between the two groups. |  | from Baseline (month 0) to month 12 | 
| Change in the Central Retinal Thickness (CRT), assessed by Spectral Domain-Optical Coherence Tomography (SD-OCT) |  | from Baseline baseline (month 0) to month 12 | 
| Total number of treatments with PDT and conbercept respectively |  | from Baseline (month 0) to month 12 | 
| Change in Best Corrected Visual Acuity (BCVA) at month 3 |  | from Baseline baseline (month 0) to month 3 | 
| Polyps regression, assessed by Indocyanine Green Angiography (ICGA) |  | from baseline (month 0) to month 3 | 
| Change in the Central Retinal Thickness (CRT), assessed by Spectral Domain-Optical Coherence Tomography (SD-OCT) |  | from baseline (month 0) to month 3 | 
| Frequency and severity of ocular and non-ocular adverse events over time. |  | from baseline (month 0) to month 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Polypoidal Choroidal Vasculopathy, Photodynamic Therapy, Conbercept, Efficacy, Safety, vascular endothelial growth factor