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

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)

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

Study Overview

• Status: Recruiting
• Conditions: Branch Retinal Vein Occlusion
• Intervention / Treatment: Drug: 601 1.25mg; Drug: ranibizumab 0.5mg

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.

• Study Type: Interventional
• Enrollment (Anticipated): 350
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Gang Tong, Bachelor of Medicine; Phone Number: 021-60790099; Email: tonggang@3s-guojian.com

Study Locations

• China
  • Beijing
    • BeiJing, Beijing, China, 100730
      • Recruiting
      • Beijing Hospital
      • Contact: Hong Dai, Bachelor; Phone Number: 010-85133308; Email: dai-hong@x263.net
      • Principal Investigator: Hong Dai
  • Guangdong
    • GuangZhou, Guangdong, China, 510630
      • Recruiting
      • The First Affiliated Hospital of Jinan University
      • Contact: JingXiang Zhong, MD
      • Principal Investigator: JingXiang Zhong
  • Henan
    • ZhengZhou, Henan, China, 450003
      • Recruiting
      • Henan Provincial Eye Hospital
      • Contact: Zongming Song, MD
      • Principal Investigator: Zongming Song
  • Hunan
    • Changsha, Hunan, China, 410011
      • Recruiting
      • The Second Xiangya Hospital of Central South University
      • Contact: BaiHua Chen, MD
      • Principal Investigator: BaiHua Chen
  • Jiangsu
    • NanJing, Jiangsu, China, 210029
      • Recruiting
      • Jiangsu Province Hospital
      • Contact: SongTao Yuan, MD
      • Principal Investigator: SongTao Yuan
  • Shanghai
    • Shanghai, Shanghai, China, 200080
      • Recruiting
      • Shanghai General Hospital
      • Contact: Hong Wang, MD
  • Sichuan
    • ChengDu, Sichuan, China, 610000
      • Recruiting
      • West China Hospital of Sichuan University
      • Contact: Fang Lu, MD; Phone Number: 86-028-85422452; Email: lufang@medicail.com.cn
      • Principal Investigator: Ming Zhang
  • Tianjin
    • TianJin, Tianjin, China, 300384
      • Recruiting
      • Tianjin Medical University Eye Hospital
      • Contact: Xiaorong Li, PhD; Phone Number: 022-23346434; Email: xiaorli@163.com
      • Principal Investigator: Xiaorong Li
    • Tianjin, Tianjin, China, 300020
      • Recruiting
      • TianJin eye hospital
      • Contact: QuanHong Han, MD
      • Principal Investigator: QuanHong Han
  • Zhejiang
    • HangZhou, Zhejiang, China, 310024
      • Recruiting
      • Zhejiang Province People's Hospital
      • Contact: MiaoQin Wu, MD
      • Principal Investigator: MiaoQin Wu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

Collaborators and Investigators

• Sponsor: Sunshine Guojian Pharmaceutical (Shanghai) Co., Ltd.
• Investigators: Principal Investigator: Xiaorong Li, MD, Tianjin Medical University Eye Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 27, 2022
• Primary Completion (Anticipated): December 1, 2025
• Study Completion (Anticipated): December 1, 2025

Study Registration Dates

• First Submitted: August 26, 2022
• First Submitted That Met QC Criteria: August 26, 2022
• First Posted (Actual): August 29, 2022

Study Record Updates

• Last Update Posted (Estimate): January 13, 2023
• Last Update Submitted That Met QC Criteria: January 11, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: Macular Edema; Retinal Vein Occlusion; Vascular Endothelial Growth Factor
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Eye Diseases; Retinal Diseases; Embolism and Thrombosis; Venous Thrombosis; Thrombosis; Retinal Vein Occlusion; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Ranibizumab
• Other Study ID Numbers: SSGJ-601-BRVO-III-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No