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Conbercept Ophthalmic Injection for Patients With Macular Edema Caused by Branch Retinal Vein Occlusion (BRAVE)

Primary Purpose

Branch Retinal Vein Occlusion, Macular Edema

Status
Completed
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
Conbercept ophthalmic injection
sham/Conbercept ophthalmic injection
Sponsored by
Chengdu Kanghong Biotech Co., Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Branch Retinal Vein Occlusion

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients have signed informed consent form and agreed to be followed up as per the trial protocol;
  • Aged ≥ 18 years, male or female;
  • Study eyes must meet all of following requirements:

    • Suffering from macular edema secondary to BRVO that involves the fovea and BRVO 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: The eye of interest is determined by the researcher from a medical point of view if both eyes of the patient meet the inclusion criteria. In principle, the eye with poor eyesight or thicker central retina should be selected as the eye of interest.

Exclusion Criteria:

Any subject who has any of the following ocular condition:

  1. Eye of interest

    • Has active retina and/or iris neovascularization;
    • Has macular epiretinal membranes or vitreous tractions which are considered to influence the central visual acuity by the researcher;
    • Has other diseases which are considered to influence the macular functional recovery by the researcher, e.g., foveal atrophy, subfoveal hemorrhage, macular hard exudates or dense submacular hard exudates;
    • Has a history of any type of retinal detachment;
    • Has non-RVO ocular diseases which are considered to possibly cause macular edema, declined visual acuity or retinal neovascularization during the study period by the researcher, e.g., wet AMD, diabetic retinopathy, uveitis/other intraocular inflammatory diseases, neovascular glaucoma and cystoid macular edema;
    • Is considered to require cataract surgery in the next 12 months by the researcher;
    • Has received intravitreal injection of corticosteroids within three months before screening, subconjunctival injection of corticosteroids within six months, or local treatment with ocular corticosteroids within one month;
    • Has received the following ophthalmic operations: scleral buckling, verteporfin-photodynamic therapy (PDT), vitrectomy, radial optic neurotomy/optic nerve sheathotomy, glaucoma filtration, parafoveal laser photocoagulation, pan-retinal photocoagulation, and macular translocation;
    • Has received YAG laser treatment or any other ophthalmic treatments (including cataract surgery, macular grid laser photocoagulation, local retinal photocoagulation, and keratoplasty) within three months before screening;
    • Has a BCVA increment by more than 10 alphabets during the screening period (BCVA tested within 24 hours before medication at Day 0 versus BCVA at the time of screening);
    • Has aphakic eye (excluding pseudophakic) or or posterior lens capsule (except YAG laser posterior capsulotomy after intraocular lens implantation);
  2. Either eye:

    • Has active periocular or ocular inflammation (e.g., blepharitis, infective conjunctivitis, keratitis, scleritis, uveitis, and endophthalmitis);
    • Has previous or existing uncontrollable glaucoma (defined as IOP remaining at ≥ 30 mmHg after anti-glaucoma treatment), or has a cup-to-disc ratio of the eye of interest of above 0.8 due to severe glaucoma;
    • Has received intravitreal injection of any anti-VEGF agents (e.g.,ranibizumab, bevacizumab, and conbercept) within three months before screening;

Patient with any of the following systemic diseases:

  • Has a history of anaphylaxis and allergy to fluorescein sodium, and of allergy to protein products for diagnosis or treatment, and is allergic to no less than two drugs and/or non-drug factors, or suffers from allergic diseases now;
  • Has a history of stroke, has a history of myocardial and/or cerebral infarction(s) and of transient cerebral ischemia within 6 months before screening, and has active and disseminated intravascular coagulation and distinct bleeding tendency;
  • Has confirmed systemic immune disease (e.g., ankylosing spondylitis, systemic lupus erythematosus, and Behcet's disease, rheumatoid arthritis, and scleroderma);
  • Has any uncontrollable clinical problem (e.g., AIDS, active hepatitis, severe mental, neurological, cardiovascular and respiratory diseases, and malignancies);
  • Hyperpietics with poor blood pressure control (defined as SBP remaining at ≥ 160 mmHg or DBP remaining ≥ 100 mmHg after antihypertensives therapy);
  • Has a surgical history within one month before screening, and/or has unhealed wounds, ulcers and fractures at present;
  • Has systemically used corticosteroids (orally, intramuscularly, intravenously) within 6 months before screening;
  • Has received systemic treatment with anti-VEGF agent(s) (e.g., bevacizumab) within 6 months before screening; Patients with any of the following abnormal laboratory tests
  • Those who have hepatic, renal and immunologic dysfunction (this trial specifies that ALT and AST are twice as high as the ULN of this central laboratory, and that Crea and BUN are 1.5-fold as high as the ULN of this central laboratory);
  • Those who have coagulation abnormalities (PT is 3 seconds greater than or equal to the ULN, and APTT is 10 seconds greater than or equal to the ULN); Patients of childbearing age with any of the following condition
  • Those who do not take effective contraceptive measures at childbearing age; Note: The following conditions are not included in the exclusion range.

    1. Amenorrhea for 12 months under the natural condition, or amenorrhea for 6 months under the natural condition and the serum FSH level of < 40 mIU/ml;
    2. Six weeks after bilateral ovariectomy with/without hysterectomy;
    3. Use of the following one or more acceptable contraceptions:

      • Sterilization (for males, with bilateral vasoligation and vasectomy)
      • Hormonal contraception (implantable, patchable, oral)
      • Intrauterine device and dural barrier method
    4. Ability to take reliable contraceptive measures over the study period and hold on to 30 days after study drug withdrawal (unacceptable contraceptive methods include: periodic continence - according to the calendar and ovulatory phase, body thermometry, post-ovulatory method, and coitus interruptus);
  • Pregnant women and breastfeeding mothers (in this trial pregnancy is defined as positive U-HCG); Others
  • Patient has participated in any drug (not including vitamins and minerals) clinical trial three months before screening (if the study drug has a long half-life, i.e., its five half-lives exceed three months, then it is deemed as five half-lives); Any condition in which the researcher deems necessary to be excluded in the study.

Sites / Locations

  • The General Hospital of the People's Liberation Army
  • Beijing Friendship Hospital, Capital Medical University
  • Peking Union Medical College Hospital
  • Peking University First Hospital
  • Peking University People's Hospital
  • Peking University Third Hospital
  • The Second Hospital of Jilin University
  • The Second Xiangya Hospital of Central South University
  • West China Hospital Sichuan University
  • Army Medical Center
  • The Second Hospital of Dalian Medical University
  • Zhongshan Ophthalmic Center, Sun Yat-Sen University
  • The Second Affiliated Hospital Zhejiang University School of Medicine
  • The 2nd Affiliated Hospital of Harbin Medical University
  • The Jiangxi Provincial People's Hospital
  • Jiangsu Province Hospital
  • Nanjing First Hospital
  • The First Affiliated Hospital of Guangxi Medical University
  • Beijing Tongren Hospital, Capital Medical University
  • Eye & Ent Hospital of Fudan University
  • Shanghai General Hospital
  • Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
  • Zhongshan Hospital
  • The First Hospital of China Medical University
  • Tianjin Eye Hospital
  • Tianjin Medical University Eye Hospital School of Optometry & Eye Institute
  • The First Affiliated Hospital of Xinjiang Medical University
  • Eye Hospital,WMU Zhejiang Eye Hospital
  • Wuhan General Hospital of Guangzhou Military Command
  • Wuxi No.2 People's Hospital
  • The First Affiliated Hospital of Xi'An

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Sham Comparator

Arm Label

Conbercept ophthalmic injection

Sham Comparator

Arm Description

Conbercept ophthalmic injection

sham / Conbercept ophthalmic injection

Outcomes

Primary Outcome Measures

Best Corrected Visual Acuity
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.

Secondary Outcome Measures

Best Corrected Visual Acuity (BCVA)
1>o evaluate mean changes in BCVA from baseline of the treatment group and the control group at month 3 and 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.
resue treament
To evaluate the number of subjects who received laser rescue treatment of the treatment group and the control group at month 6 and 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.
distribution of BCVA changes
To evaluate the distribution of BCVA changes from baseline of the treatment group and the control group at month 3, 6 and 12.
mean changes in BCVA
To evaluate mean changes in BCVA from baseline of the treatment group and the control group at every visit.
Change in image
To evaluate the average changes in imaging findings (e.g., CRT and total macular volume) relative to the baseline for treatment group and control group at each follow-up visit.

Full Information

First Posted
February 8, 2017
Last Updated
July 13, 2022
Sponsor
Chengdu Kanghong Biotech Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT03108352
Brief Title
Conbercept Ophthalmic Injection for Patients With Macular Edema Caused by Branch Retinal Vein Occlusion
Acronym
BRAVE
Official Title
Multi-center, Randomized, Double-masked, Placebo-controlled Phase III Clinical Study of Conbercept Ophthalmic Injection for Patients With BRVO.
Study Type
Interventional

2. Study Status

Record Verification Date
July 2022
Overall Recruitment Status
Completed
Study Start Date
April 13, 2016 (Actual)
Primary Completion Date
April 13, 2020 (Actual)
Study Completion Date
October 16, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Chengdu Kanghong Biotech Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to verify the efficacy and safety of intravitreal injection of conbercept in patients with macular edema (ME) caused by branch retinal vein occlusion (BRVO).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Branch Retinal Vein Occlusion, Macular Edema

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderOutcomes Assessor
Allocation
Randomized
Enrollment
255 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Conbercept ophthalmic injection
Arm Type
Experimental
Arm Description
Conbercept ophthalmic injection
Arm Title
Sham Comparator
Arm Type
Sham Comparator
Arm Description
sham / Conbercept ophthalmic injection
Intervention Type
Drug
Intervention Name(s)
Conbercept ophthalmic injection
Intervention Description
Conbercept ophthalmic injection at a dose of 0.5 mg every month(day0-month 5); If sbujects meets the criteria for repeated administration, the subject receives 0.5 mg Conbercept injection into the study eye (Month 6 ~ 11)
Intervention Type
Other
Intervention Name(s)
sham/Conbercept ophthalmic injection
Intervention Description
Sham injection every month (Day 0 - Month 5); 0.5 mg Conbercept ophthalmic injection in month 6; If sbujects meets the criteria for repeated administration, the subject receives 0.5 mg Conbercept injection into the study eye (Month 7 ~ 11)
Primary Outcome Measure Information:
Title
Best Corrected Visual Acuity
Description
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.
Time Frame
month 6
Secondary Outcome Measure Information:
Title
Best Corrected Visual Acuity (BCVA)
Description
1>o evaluate mean changes in BCVA from baseline of the treatment group and the control group at month 3 and 12.
Time Frame
month 3 and month 12
Title
Central Retinal Thickness
Description
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.
Time Frame
month 3, month 6 and month 12
Title
resue treament
Description
To evaluate the number of subjects who received laser rescue treatment of the treatment group and the control group at month 6 and 12.
Time Frame
month 6 and month 12
Title
Number of participants with treatment-related the systemic and ocular safely as assessed
Description
To evaluate the systemic and ocular safety of the treatment group and the control group.
Time Frame
up to 12.5 months
Title
distribution of BCVA changes
Description
To evaluate the distribution of BCVA changes from baseline of the treatment group and the control group at month 3, 6 and 12.
Time Frame
month 3, month 6 and month 12
Title
mean changes in BCVA
Description
To evaluate mean changes in BCVA from baseline of the treatment group and the control group at every visit.
Time Frame
month 0,month 1,month 2,month 3,month 4,month 5,month 6,month 7,month 8,month 9,month 10,month 11 and month 12
Title
Change in image
Description
To evaluate the average changes in imaging findings (e.g., CRT and total macular volume) relative to the baseline for treatment group and control group at each follow-up visit.
Time Frame
month 0,month 1,month 2,month 3,month 4,month 5,month 6,month 7,month 8,month 9,month 10,month 11 and month 12
Other Pre-specified Outcome Measures:
Title
Immunogenic positive response in the treatment group
Description
Number of participants with Treatment-Ralated positive response to anti-drug antibody(ADA)or neutralizing antibody(Nab) in the treatment group at baseline,6 and 12months.
Time Frame
baseline,month 6, month 12
Title
Immunogenic positive response in the control group
Description
Number of participants with Treatment-Ralated positive response to anti-drug antibody(ADA)or neutralizing antibody(Nab) in thecontrol group at baseline,6 and 12months.
Time Frame
baseline,month 6, month 12
Title
safety analysis of immunogenic positive response
Description
To analyze the safely of subjects with positive response to ADA or Nab at 12 months after treatment and number of participants with positive respone who develop anticipants immuogenic adverse events.
Time Frame
month 12
Title
safety analysis of immunogenic negative response
Description
To analyze the safely of subjects with negative response to ADA or Nab at 12 months after treatment and number of participants with negative response who develop anticipants immuogenic adverse events.
Time Frame
month 12
Title
Best Corrected Visual Acuity (BCVA)
Description
To analyze the BCVA for subjects with positive response to ADA or Nab at 12 months after treatment.
Time Frame
month 12

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients have signed informed consent form and agreed to be followed up as per the trial protocol; Aged ≥ 18 years, male or female; Study eyes must meet all of following requirements: Suffering from macular edema secondary to BRVO that involves the fovea and BRVO 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: The eye of interest is determined by the researcher from a medical point of view if both eyes of the patient meet the inclusion criteria. In principle, the eye with poor eyesight or thicker central retina should be selected as the eye of interest. Exclusion Criteria: Any subject who has any of the following ocular condition: Eye of interest Has active retina and/or iris neovascularization; Has macular epiretinal membranes or vitreous tractions which are considered to influence the central visual acuity by the researcher; Has other diseases which are considered to influence the macular functional recovery by the researcher, e.g., foveal atrophy, subfoveal hemorrhage, macular hard exudates or dense submacular hard exudates; Has a history of any type of retinal detachment; Has non-RVO ocular diseases which are considered to possibly cause macular edema, declined visual acuity or retinal neovascularization during the study period by the researcher, e.g., wet AMD, diabetic retinopathy, uveitis/other intraocular inflammatory diseases, neovascular glaucoma and cystoid macular edema; Is considered to require cataract surgery in the next 12 months by the researcher; Has received intravitreal injection of corticosteroids within three months before screening, subconjunctival injection of corticosteroids within six months, or local treatment with ocular corticosteroids within one month; Has received the following ophthalmic operations: scleral buckling, verteporfin-photodynamic therapy (PDT), vitrectomy, radial optic neurotomy/optic nerve sheathotomy, glaucoma filtration, parafoveal laser photocoagulation, pan-retinal photocoagulation, and macular translocation; Has received YAG laser treatment or any other ophthalmic treatments (including cataract surgery, macular grid laser photocoagulation, local retinal photocoagulation, and keratoplasty) within three months before screening; Has a BCVA increment by more than 10 alphabets during the screening period (BCVA tested within 24 hours before medication at Day 0 versus BCVA at the time of screening); Has aphakic eye (excluding pseudophakic) or or posterior lens capsule (except YAG laser posterior capsulotomy after intraocular lens implantation); Either eye: Has active periocular or ocular inflammation (e.g., blepharitis, infective conjunctivitis, keratitis, scleritis, uveitis, and endophthalmitis); Has previous or existing uncontrollable glaucoma (defined as IOP remaining at ≥ 30 mmHg after anti-glaucoma treatment), or has a cup-to-disc ratio of the eye of interest of above 0.8 due to severe glaucoma; Has received intravitreal injection of any anti-VEGF agents (e.g.,ranibizumab, bevacizumab, and conbercept) within three months before screening; Patient with any of the following systemic diseases: Has a history of anaphylaxis and allergy to fluorescein sodium, and of allergy to protein products for diagnosis or treatment, and is allergic to no less than two drugs and/or non-drug factors, or suffers from allergic diseases now; Has a history of stroke, has a history of myocardial and/or cerebral infarction(s) and of transient cerebral ischemia within 6 months before screening, and has active and disseminated intravascular coagulation and distinct bleeding tendency; Has confirmed systemic immune disease (e.g., ankylosing spondylitis, systemic lupus erythematosus, and Behcet's disease, rheumatoid arthritis, and scleroderma); Has any uncontrollable clinical problem (e.g., AIDS, active hepatitis, severe mental, neurological, cardiovascular and respiratory diseases, and malignancies); Hyperpietics with poor blood pressure control (defined as SBP remaining at ≥ 160 mmHg or DBP remaining ≥ 100 mmHg after antihypertensives therapy); Has a surgical history within one month before screening, and/or has unhealed wounds, ulcers and fractures at present; Has systemically used corticosteroids (orally, intramuscularly, intravenously) within 6 months before screening; Has received systemic treatment with anti-VEGF agent(s) (e.g., bevacizumab) within 6 months before screening; Patients with any of the following abnormal laboratory tests Those who have hepatic, renal and immunologic dysfunction (this trial specifies that ALT and AST are twice as high as the ULN of this central laboratory, and that Crea and BUN are 1.5-fold as high as the ULN of this central laboratory); Those who have coagulation abnormalities (PT is 3 seconds greater than or equal to the ULN, and APTT is 10 seconds greater than or equal to the ULN); Patients of childbearing age with any of the following condition Those who do not take effective contraceptive measures at childbearing age; Note: The following conditions are not included in the exclusion range. Amenorrhea for 12 months under the natural condition, or amenorrhea for 6 months under the natural condition and the serum FSH level of < 40 mIU/ml; Six weeks after bilateral ovariectomy with/without hysterectomy; Use of the following one or more acceptable contraceptions: Sterilization (for males, with bilateral vasoligation and vasectomy) Hormonal contraception (implantable, patchable, oral) Intrauterine device and dural barrier method Ability to take reliable contraceptive measures over the study period and hold on to 30 days after study drug withdrawal (unacceptable contraceptive methods include: periodic continence - according to the calendar and ovulatory phase, body thermometry, post-ovulatory method, and coitus interruptus); Pregnant women and breastfeeding mothers (in this trial pregnancy is defined as positive U-HCG); Others Patient has participated in any drug (not including vitamins and minerals) clinical trial three months before screening (if the study drug has a long half-life, i.e., its five half-lives exceed three months, then it is deemed as five half-lives); Any condition in which the researcher deems necessary to be excluded in the study.
Facility Information:
Facility Name
The General Hospital of the People's Liberation Army
City
Beijing
State/Province
Beijing
Country
China
Facility Name
Beijing Friendship Hospital, Capital Medical University
City
Beijing
Country
China
Facility Name
Peking Union Medical College Hospital
City
Beijing
Country
China
Facility Name
Peking University First Hospital
City
Beijing
Country
China
Facility Name
Peking University People's Hospital
City
Beijing
Country
China
Facility Name
Peking University Third Hospital
City
Beijing
Country
China
Facility Name
The Second Hospital of Jilin University
City
Changchun
Country
China
Facility Name
The Second Xiangya Hospital of Central South University
City
Changsha
Country
China
Facility Name
West China Hospital Sichuan University
City
Chengdu
Country
China
Facility Name
Army Medical Center
City
Chongqing
Country
China
Facility Name
The Second Hospital of Dalian Medical University
City
Dalian
Country
China
Facility Name
Zhongshan Ophthalmic Center, Sun Yat-Sen University
City
Guangzhou
Country
China
Facility Name
The Second Affiliated Hospital Zhejiang University School of Medicine
City
Hangzhou
Country
China
Facility Name
The 2nd Affiliated Hospital of Harbin Medical University
City
Harbin
Country
China
Facility Name
The Jiangxi Provincial People's Hospital
City
Nanchang
Country
China
Facility Name
Jiangsu Province Hospital
City
Nanjing
Country
China
Facility Name
Nanjing First Hospital
City
Nanjing
Country
China
Facility Name
The First Affiliated Hospital of Guangxi Medical University
City
Nanning
Country
China
Facility Name
Beijing Tongren Hospital, Capital Medical University
City
Peking
Country
China
Facility Name
Eye & Ent Hospital of Fudan University
City
Shanghai
Country
China
Facility Name
Shanghai General Hospital
City
Shanghai
Country
China
Facility Name
Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
City
Shanghai
Country
China
Facility Name
Zhongshan Hospital
City
Shanghai
Country
China
Facility Name
The First Hospital of China Medical University
City
Shenyang
Country
China
Facility Name
Tianjin Eye Hospital
City
Tianjing
Country
China
Facility Name
Tianjin Medical University Eye Hospital School of Optometry & Eye Institute
City
Tianjin
Country
China
Facility Name
The First Affiliated Hospital of Xinjiang Medical University
City
Urumqi
Country
China
Facility Name
Eye Hospital,WMU Zhejiang Eye Hospital
City
Wenzhou
Country
China
Facility Name
Wuhan General Hospital of Guangzhou Military Command
City
Wuhan
Country
China
Facility Name
Wuxi No.2 People's Hospital
City
Wuxi
Country
China
Facility Name
The First Affiliated Hospital of Xi'An
City
Xi'an
Country
China

12. IPD Sharing Statement

Citations:
PubMed Identifier
32633861
Citation
Shalchi Z, Mahroo O, Bunce C, Mitry D. Anti-vascular endothelial growth factor for macular oedema secondary to branch retinal vein occlusion. Cochrane Database Syst Rev. 2020 Jul 7;7(7):CD009510. doi: 10.1002/14651858.CD009510.pub3.
Results Reference
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Learn more about this trial

Conbercept Ophthalmic Injection for Patients With Macular Edema Caused by Branch Retinal Vein Occlusion

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