A Phase III Study for 601 Versus Ranibizumab in Patients With Vision Loss

Study Overview
=================
Brief Summary
-----------------
To compare the efficacy and safety of recombinant humanized anti-VEGF monoclonal antibody (601) with Ranibizumab in patients with macular edema secondary to BRVO

Detailed Description
-----------------
After a up to 14-day screening period, patients will be randomized allocated in 2 groups at 1:1 ratio and followed up for 52 weeks. Followed-up visits will be scheduled at a 4-week interval. After 6 initial monthly injections of 601 or ranibizumab (loading phase), subjects will enter an individualized flexible treatment (IFT) phase (week 24 to week 48). During the IFT phase, subjects will receive either the injections or not based on the assessment of disease stability at each visit. Efficacy and safety outcomes will be evaluated up to a period of 52 weeks.

Official Title
-----------------
A Randomized, Double Masked, Multicenter, Phase III Study Assessing the Efficacy and Safety of 601 Versus Ranibizumab in Patients With Macular Edema Secondary to Branch Retinal Vein Occlusion (BRVO)

Conditions
-----------------
Branch Retinal Vein Occlusion

Intervention / Treatment
-----------------
* Drug: 601 1.25mg
* Drug: ranibizumab 0.5mg


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Sign informed consent form and willing to be followed up at the time specified in the trial Male or Female, at least 18 years of age The study eye must meet the following criteria：Diagnosed with macular edema secondary to Branch retinal vein occlusion (BRVO) or Hemi-retinal vein occlusion (HRVO) within 12 months; BCVA score ≤ 73 and ≥19 letters using ETDRS visual acuity testing charts (approximate Snellen equivalent of 20/40 to 20/400); CRT ≥ 250μm; No optometric media opacity and pupil abnormal BCVA score ≥ 34 ETDRS letters (approximate Snellen equivalent of 20/200) in the fellow eye, with no active RVO disease. Exclusion Criteria: For Study Eye: Concomitant conditions or ocular disorders in the study eye at screening or baseline which could, in the opinion of the investigator, prevent response to study treatment or may confound interpretation of study results, compromise visual acuity or require medical or surgical intervention during the 52-week study period For Study Eye: iris, chamber angle neovascularization or retinal, optic disc neovascularization For Study Eye: Previous use of intraocular or periocular steroids within 3 months prior to baseline, or dexamethasone intravitreal implant within 6 months prior to baseline For Study Eye: Macular laser photocoagulation (focal/grid)，panretinal laser photocoagulation，vitrectomy，trabeculectomy or keratoplasty in the study eye at any time prior to baseline. YAG laser treatment or any other intraocular surgeries (e.g. cataract surgery) in the study eye within 3 months prior to the baseline For Study Eye: During the screening period, the BCVA is >10 letters improved For Study Eye: Aphakia (except IOL) or posterior capsular defect (except YAG posterior capsulotomy after intraocular lens implantation surgery) For Any Eye: Active ocular infections (e.g. blepharitis, conjunctivitis, keratitis, scleritis, uveitis, endophthalmitis) in any eye For Any Eye: Uncontrolled glaucoma (defined as intraocular pressure after antiglaucoma therapy ≥ 25mmHg) in any eye, or the cup/disk ratio >0.8 in the study eye For Any Eye: History of intravitreal use of anti-VEGF drugs (e.g. ranibizumab，bevacizumab，aflibercept, conbercept, etc.) in any eye within 3 months prior to baseline History of allergy to fluorescein sodium and allergies to protein products for treatment or diagnosis History of stroke (cerebrovascular accident), myocardial infarction, active disseminated intravascular coagulation or pronounced bleeding tendency in the past 6 months prior to baseline Systemic immune diseases (e.g. ankylosing spondylitis, systemic lupus erythematosus, Behcet's disease, rheumatoid arthritis, scleroderma etc.) Any uncontrolled clinical conditions (e.g. AIDS, active hepatitis, serious mental, neurological, cardiovascular, respiratory and other systemic diseases or malignant tumors, etc.). Malignant tumors with no metastasis or recurrence within 5 years or cancers in situ cancers are not excluded. Uncontrolled blood pressure (defined as systolic blood pressure ≥ 160 mmHg or diastolic pressure ≥ 100 mmHg after antihypertensive medication History of surgery (except for healed minimally invasive surgery) and/or currently have unhealed wounds, moderate to severe ulcers, fractures, etc. within 1 month prior to baseline History of system use of anti-VEGF drugs (e.g. bevacizumab) within 3 months prior to baseline Liver dysfunction (ALT or AST is 2 times higher than the upper limit of normal value in the local laboratory). Renal function impairment (Cr is 1.5 times higher than the upper limit of normal values in the local laboratory) Abnormal coagulation function (prothrombin time ≥ the upper limit of normal value for 3 seconds) and activated partial thromboplastin time ≥ the upper limit of normal value for 10 seconds). Non-use of effective contraception during childbearing age (except for women with spontaneous admonishment of more than 12 months) Women in pregnancy and lactation Participation in clinical trials of any drug (except vitamins and minerals) or medical devices in the past 1 month or 5 half-lifes if the drug has a long half-life >1 month prior to baseline. Any conditions that researchers think it needs to be ruled out

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 601 1.25mg<br>loading phase (6 months): 601 1.25mg/eye/time, Intravitreal injection, administered once every 4 weeks for 6 consecutive doses | Drug: 601 1.25mg<br>* loading phase (6 months): 601 1.25mg/eye/time, Intravitreal injection, administered once every 4 weeks for 6 consecutive doses<br>* Other names: 601;|
| Active Comparator: ranibizumab 0.5mg<br>loading phase (6 months): ranibizumab 0.5mg/eye/time, Intravitreal injection, administered once every 4 weeks for 6 consecutive doses | Drug: ranibizumab 0.5mg<br>* loading phase (6 months): ranibizumab 0.5mg/eye/time, Intravitreal injection, administered once every 4 weeks for 6 consecutive doses<br>* Other names: Lucentis;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| best-corrected visual acuity (BCVA) | Assessed with Early treatment diabetic retinopathy study (ETDRS) visual acuity testing charts. | From Baseline to Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| best-corrected visual acuity (BCVA) | Assessed with Early treatment diabetic retinopathy study (ETDRS) visual acuity testing charts. | up to 52 weeks | 
| central retinal thickness (CRT) | SD-OCT (spectral domain optical coherence tomography) was used to assess the average retinal thickness of the central 1 mm diameter subfield around the foveal center. | up to 52 weeks | 
| Number of injections | Number of administered injections for 601 or ranibizumab | up to 52 weeks | 
| Adverse Events (AEs) | All adverse events related to 601 or ranibizumab observed through various tests (including blood routine, pregnancy test, electrocardiogram, etc.) | up to 52 weeks | 
| Steady-state Blood concentrations of 601 or ranibizumab | Detect the steady-state blood concentrations of 601 or ranibizumab through the subject's blood sample | up to 52 weeks | 
| Blood concentrations of Vascular Endothelial Growth Factor (VEGF) | Detect the blood concentrations of VEGF through the subject's blood sample | up to 52 weeks | 
| anti-drug antibody (ADA) of 601 | Detect the presence of anti-drug antibody (ADA) of 601 through the subject's blood sample. ADA-positive subjects will also undergo further Neutralization antibody (Nab) testing. | up to 52 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Retinal Vein Occlusion, Macular Edema, Vascular Endothelial Growth Factor