Head to Head Study of Anti-VEGF Treatment.

Study Overview
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Brief Summary
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An exploratory single site, open label, randomized, controlled study evaluated plasma vascular endothelial growth factor levels after intravitreal injection of ranibizumab (Lucentis) and conbercept (Langmu) for neovascular age-related macular degeneration

Detailed Description
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This prospective, randomized, open label study enrolled patients with neovascular AMD who were naïve to anti-VEGF therapy or have not received intravitreal anti-VEGF therapy for the previous 3 months. Patients were randomized in two treatment arms for 3 months: Study arm 1: Three monthly injections of 0.5mg Ranibizumab Study arm 2: Three monthly injections of 0.5mg Conbercept Blood sample (plasma/serum) was collected at baseline (pre-dose), 3h post-injections and days 1, 3, 7 and 28, following doses 1 and 3 for PK and systemic VEGF analysis. The lab staff was blinded for treatment allocation. Plasma VEGF concentration was measured by a blinded laboratory using Quantikine® ELISA kits. Serum ranibizumab and conbercept concentration will be determined using validated ELISA assay. The study was divided into 2 stages: the 1st initial feasibility stage with 6 patients per arm (12 patients in total) to verify SD for sample size justification and 2nd stage to confirm the findings with justified sample size.

Official Title
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An Exploratory Single Site, Open Label, Randomized, Controlled Study to Evaluate Plasma Vascular Endothelial Growth Factor Levels After Intravitreal Injection of Ranibizumab (Lucentis) and Conbercept (Langmu) for nAMD

Conditions
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Age-related Macular Degeneration

Intervention / Treatment
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* Drug: ranibizumab
* Drug: Conbercept


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent must be obtained before any assessment is performed. Male or female patient ≥ 50 years of age. Subfoveal CNV secondary to nAMD. BCVA score must be between 73 and 24 letters as measured by ETDRS chart Exclusion Criteria: For both eyes Any active periocular or ocular infection or inflammation Uncontrolled glaucoma Neovascularization of the iris or neovascular glaucoma. For study eye Choroidal neovascularization of any other cause than wet AMD Ocular disorders present that may confound interpretation of study results, Previous treatment with verteporfin PDT (Visudyne®), external-beam radiation therapy, focal laser photocoagulation, vitrectomy, submacular surgery, or transpupillary thermotherapy. Structural damage within 0.5 disc diameter of the center of the macula Atrophy or fibrosis involving the center of the fovea. Inability of obtaining required lab report. Ocular medical history History of intravitreal injection with any anti-VEGF drugs within 3 months. Exclusion criteria for systemic medical conditions and treatment Any type of systemic disease or its treatment Any patients diagnosed with tumor. Stroke or myocardial infarction less than 3 months. Known hypersensitivity to indocyanine green, fluorescein, or any component of the investigational drug formulation. Use of any systemic anti-VEGF drugs within 6 months. Exclusion criteria for patient Patients who have participated in other investigational drug study within 60 days. Pregnant or nursing (lactating) women. Inability to comply with study or follow-up procedures.
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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ranibizumab 0.5 mg<br>Three monthly injections of 0.5mg Ranibizumab | Drug: ranibizumab<br> <br> * Other names: Lucentis;|
| Active Comparator: Conbercept 0.5 mg<br>Three monthly injections of 0.5mg Conbercept | Drug: Conbercept<br> <br> * Other names: Langmu;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Plasma Vascular Endothelial Growth Factor (VEGF) Concentration After First Injection at Visit 5 (Day 8 +/- 1 Day) | Change from baseline in plasma Vascular endothelial growth factor (VEGF) concentration after first injection at Visit 5 (Day 8 +/- 1 day).Blood sample was collected for systemic VEGF. VEGF was measured by a blinded laboratory using ELISA kits. | Baseline, Visit 5 (Day 8 +/- 1 day) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Plasma Vascular Endothelial Growth Factor (VEGF) Concentration After Third Injection at Visit 10 (Day 67 +/- 1 Day) | Change from baseline in plasma Vascular endothelial growth factor (VEGF) concentration after third injection at Visit 10 (Day 67 +/- 1 day). Blood sample was collected for systemic VEGF. VEGF will be measured by a blinded laboratory using ELISA kits. | Baseline, Visit 10 (Day 67 +/- 1 day) | 
| Plasma VEGF Concentration at Baseline, Visit 2, 3, 4, 5, 6 After 1st Injection | Blood sample will be collected for systemic VEGF. VEGF will be measured by a blinded laboratory using ELISA kits. Baseline, Visit Visit 2, 3, 4, 5, 6 after 1st injection | Baseline, Visit 2, 3, 4, 5, 6 | 
| Plasma VEGF Concentration at Baseline, Visit 7, 8, 9, 10, 11 After 3rd Injection | Blood sample will be collected for systemic VEGF. VEGF will be measured by a blinded laboratory using ELISA kits. Baseline, Visit 7, 8, 9, 10, 11 after 3rd injection | Baseline, Visit 7, 8, 9, 10, 11 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Age-related macular degeneration,, ranibizumab,, conbercept,, plasma VEGF, PK