Conbercept Ophthalmic Injection for Patients of Central Retinal Vein Occlusion

Study Overview
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Brief Summary
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This study evaluates the efficacy and safety of Conbercept ophthalmic injection. This is a multi-center, randomized, double-masked, placebo-controlled phase III clinical study. 237 patients with central retinal vein occlusion(CRVO) are expected to be enrolled in the study and randomly assigned into the Conbercept ophthalmic injection treatment group or the control group at a ratio of 2:1.

Detailed Description
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The trial is divided into core and extension periods. Core period (Day 0 - Month 5): Eligible subjects after the screening are assigned into the group to receive either intravitreal injection of Conbercept ophthalmic injection at a dose of 0.5 mg (treatment group) or a sham injection (control group) into their study eyes every month (Day 0 - Month 5). At month 6, primary endpoint are judged by investigators. Extension period (Month 6   12): Subjects in treatment group are reviewed monthly, if he/she meets the criteria for repeated administration, the subject receives 0.5 mg Conbercept injection into the study eye (Month 6   11). Subjects in control group receive a single intravitreal injection of 0.5 mg Conbercept ophthalmic injection in month 6, followed monthly review, if he/she meets the criteria for repeated administration, the subject receives 0.5 mg Conbercept injection into the study eye (Month 6   11). The final evaluation is performed at the end of Month 12.

Official Title
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An Efficacy and Safety Trial of Intravitreal Injection of Conbercept Ophthalmic Injection in Treatment of Macular Edema Secondary to Central Retinal Vein Occlusion

Conditions
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Macular Edema, Central Retinal Vein Occlusion

Intervention / Treatment
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* Drug: Conbercept Ophthalmic Injection
* Drug: sham injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients have signed informed consent and agreed to be followed up as per the trial protocol; Aged ≥ 18 years, male or female; Target eyes must meet all of following requirements: Suffering from macular edema secondary to CRVO or HRVO that involves the fovea and has been first diagnosed within previous 12 months; Best corrected visual acuity (BCVA) ≥24 and ≤73 letters (Snellen equivalent is 20 / 320-20 / 40); Central retinal thickness (CRT) on OCT is ≥300 μm; Without opacities in the refractive media and pupillary miosis that affects fundus examination. Note: If both eyes of a subject meet the inclusion criteria, the target eye shall be determined by investigators from a medical point of view. Exclusion Criteria: Patients who present with any the following ocular conditions: - Study eyes Active retinal or iris neovascularization; Epiretinal membrane or vitreomacular traction that investigators consider likely to affect central vision; Other ocular diseases or conditions that may affect the recovery of the macula functions based on the opinion of investigators, such as foveal atrophy, foveal hemorrhage, foveal hard exudates, or dense submacular hard exudates, etc.; History of retinal detachment; Suffering from non-RVO diseases that may result in macular edema, visual acuity loss or retinal neovascularization during the study period based on the opinion of investigators, such as wet AMD, diabetic retinopathy, uveitis or other ocular inflammatory diseases, neovascular glaucoma, and cystoid macular edema, etc.; Patients with cataract whose eye is likely to require cataract surgery within the next 12 months; Have received intraocular injection of corticosteroid within previous 3 months, received subconjunctiva injection of corticosteroid within previous 6 months, or received ocular corticosteroid therapy within previous 1 month; Have undergone any of the following ocular surgeries: scleral buckling surgery, PDT, vitrectomy, radial optic neurotomy or sheathotomy, glaucoma filtration surgery, parafoveal photocoagulation, pan-retinal photocoagulation, and macular translocation surgery, etc.; Have received YAG laser surgery or any other ocular surgery (which including cataract surgery, macular grid photocoagulation, local retinal photocoagulation, and corneal implantation, etc.) within previous 3 months; Improvement of BCVA>10 letters during screening period (comparing BCVA that is measured within 24h before first administration (Day 0) to that measured at enrollment); Without lens (excluding intraocular lens) or with posterior lens capsule defect (excluding YAG laser capsulotomy following intraocular lens implantation); - Either eye of patients： Suffering from active periophthalmitis or ocular inflammation (such as blepharitis, infectious conjunctivitis, keratitis, scleritis, uveitis and endophthalmitis, etc.); Had or have uncontrollable glaucoma (defined as intraocular pressure remains ≥30 mmHg after anti-glaucoma treatment), or study eye with the cup-to-disc ratio > 0.8 due to severe glaucoma; Have received anti-VEGF medications (such as Lucentis, Avastin, or Conbercept, etc.) within 3 months before screening; - Patients who present with any the following systematic conditions: Patients have allergic reaction or history of allergy to sodium fluorescein, have a history of allergy to protein products for therapy or diagnosis, and are sensitized to two or more drugs and/or non-drug factors, or suffering from allergic diseases; Patients with a history of stroke, or with a history of myocardial infarction and/or cerebrovascular disease or a history of transient cerebral ischemia within 6 months before screening, or with active disseminated intravascular coagulation and significant bleeding tendencies; Patients who are diagnosed with systemic autoimmune diseases (such as ankylosing spondylitis, systemic lupus erythematosus, Behcet's disease, rheumatoid arthritis, and scleroderma, etc.)； Patients who are diagnosed with any clinically uncontrollable disease (such as HIV, active hepatitis, metabolic disorders, severe mental, neurological, cardiovascular, respiratory and other diseases and cancer); Hypertensive patients whose blood pressure have not been controlled effectively (defined as SBP ≥160 mmHg or DBP ≥100 mmHg after treatment with antihypertensive drugs); Patient who has a surgical history within 1 month before enrollment, and/or is currently suffering from unhealed wounds, ulcers, fractures, etc.; Use of systemic (orally, intramuscularly or intravenously) corticosteroids within 6 months before screening; Patients received systemic anti-VEGF medications (such as Avastin) within 6 months before screening; Patients underwent laboratory test with any of the following abnormal results Liver, kidney and immune dysfunction (defined as ALT and AST ≥ 2 × UNL of the laboratory , Crea and BUN ≥ 1.5 × UNL of the laboratory in the site of this trial); Coagulation abnormalities (prothrombin time ≥ 3 seconds + UNL, and active partly thromboplastin time ≥ 10 seconds + UNL); Patients of childbearing age under any of the following conditions: Do not use an effective method of contraception; Note: subject with the following conditions are not excluded: 12 months of amenorrhea for natural reasons, or 6 months of natural amenorrhea for natural reasons and levels of serum follicle stimulating hormone <40mlU/ml; 6 weeks after ovariectomy of both sides with / without concurrent hysterectomy; Use one or more acceptable birth control methods as follows: Sterilization (male companion has undergone bilateral vasectomy or resection) Hormonal birth control (implantable, patch or oral route) Intrauterine device and double barrier methods Take reliable birth control measures throughout the study period, and continuously do so for 30 d after stopping study medication (unacceptable birth control methods including periodic abstinence, calendar-based method, ovulation phase method, body temperature measurement, luteal phase method and onanism); Pregnant and breast-feeding women. Pregnancy is defined as a positive urine pregnancy test in this trial; Others Participate in any drug (exclusive of vitamins and minerals) clinical trial within 3 months prior to the screening (if the investigational drug has a long half-life, 3 months or 5 half-lives, whichever is longer); The Subject is otherwise determined by the Investigator to be medically unsuitable for participation in this study.

Ages Eligible for Study
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Minimum Age: 18 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Conbercept<br>Conbercept | Drug: Conbercept Ophthalmic Injection<br>* Subject receive 0.5 mg Conbercept injection into their study eyes every month (Day 0 - Month 5). If subjects meets the criteria for repeated administration, the subject receives 0.5 mg Conbercept injection into the study eye (Month 6   11).<br>|
| Sham Comparator: Conbercept or sham<br>Conbercept or sham | Drug: Conbercept Ophthalmic Injection<br>* Subject receive 0.5 mg Conbercept injection into their study eyes every month (Day 0 - Month 5). If subjects meets the criteria for repeated administration, the subject receives 0.5 mg Conbercept injection into the study eye (Month 6   11).<br>Drug: sham injection<br>* Subjects receive sham injection into their study eyes every month (Day 0 - Month 5). Subjects receive a single intravitreal injection of 0.5 mg Conbercept ophthalmic injection in month 6, followed monthly review, if he/she meets the criteria for repeated administration, the subject receives 0.5 mg Conbercept injection into the study eye (Month 6   11).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Corrected Visual Acuity | To compare mean changes in Best Corrected Visual Acuity (BCVA) from baseline between the Conbercept ophthalmic injection treatment group (treatment group) and the control group at month 6. | month 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Corrected Visual Acuity | To evaluate mean changes in BCVA from baseline of the treatment group and the control group at month 3 and 12. | month 3 and month 12 | 
| Central Retinal Thickness | To evaluate mean changes in Central Retinal Thickness (CRT) from baseline of the treatment group and the control group at month 3, 6 and 12. | month 3, month6 and month 12 | 
| Number of subject who received laser rescue treatment | To evaluate the number of subjects who received laser rescue treatment of the treatment group and the control group at month 6 and 12. | month 6 and month 12 | 
| Number of participants with treatment-related the systemic and ocular safely as assessed | To evaluate the systemic and ocular safety of the treatment group and the control group. | month 6 and month 12 or trail period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Conbercept ophthalmic injection, ME, CRVO