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Conbercept Ophthalmic Injection for Patients of Central Retinal Vein Occlusion (CRAVE)

Primary Purpose

Macular Edema, Central Retinal Vein Occlusion

Status
Completed
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
Conbercept Ophthalmic Injection
sham 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 Macular Edema focused on measuring Conbercept ophthalmic injection, ME, CRVO

Eligibility Criteria

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

Inclusion Criteria:

  1. Patients have signed informed consent and agreed to be followed up as per the trial protocol;
  2. Aged ≥ 18 years, male or female;
  3. 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;
  4. 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

  1. Active retinal or iris neovascularization;
  2. Epiretinal membrane or vitreomacular traction that investigators consider likely to affect central vision;
  3. 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.;
  4. History of retinal detachment;
  5. 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.;
  6. Patients with cataract whose eye is likely to require cataract surgery within the next 12 months;
  7. 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;
  8. 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.;
  9. 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;
  10. 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);
  11. Without lens (excluding intraocular lens) or with posterior lens capsule defect (excluding YAG laser capsulotomy following intraocular lens implantation);

    - Either eye of patients:

  12. Suffering from active periophthalmitis or ocular inflammation (such as blepharitis, infectious conjunctivitis, keratitis, scleritis, uveitis and endophthalmitis, etc.);
  13. 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;
  14. 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:

  15. 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;
  16. 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;
  17. Patients who are diagnosed with systemic autoimmune diseases (such as ankylosing spondylitis, systemic lupus erythematosus, Behcet's disease, rheumatoid arthritis, and scleroderma, etc.);
  18. 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);
  19. Hypertensive patients whose blood pressure have not been controlled effectively (defined as SBP ≥160 mmHg or DBP ≥100 mmHg after treatment with antihypertensive drugs);
  20. Patient who has a surgical history within 1 month before enrollment, and/or is currently suffering from unhealed wounds, ulcers, fractures, etc.;
  21. Use of systemic (orally, intramuscularly or intravenously) corticosteroids within 6 months before screening;
  22. 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
  23. 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);
  24. 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:

  25. 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);
  26. Pregnant and breast-feeding women. Pregnancy is defined as a positive urine pregnancy test in this trial; Others
  27. 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);
  28. The Subject is otherwise determined by the Investigator to be medically unsuitable for participation in this study.

Sites / Locations

  • Beijing Friendship Hospital,Capital Medical University
  • Beijing Tongren Hospital, Capital Medical University
  • Peking Union Medical College Hospital
  • Peking University First Hospital
  • Peking University People's Hospital
  • Peking University Third Hospital
  • The General Hospital of the People's Liberation Army
  • 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
  • The 2nd Affiliated Hospital of Harbin Medical University
  • The Jiangxi Provincial People's Hospital
  • Nanjing First Hospital
  • The First Affiliated Hospital of Guangxi Medical University
  • Eye & Ent Hospital of Fudan University
  • Shanghai General Hospital
  • 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
  • The First Affiliated Hospital of Xi'An Jiaotong University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Sham Comparator

Arm Label

Conbercept

Conbercept or sham

Arm Description

Conbercept

Conbercept or sham

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.

Full Information

First Posted
February 8, 2017
Last Updated
July 11, 2022
Sponsor
Chengdu Kanghong Biotech Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT03223714
Brief Title
Conbercept Ophthalmic Injection for Patients of Central Retinal Vein Occlusion
Acronym
CRAVE
Official Title
An Efficacy and Safety Trial of Intravitreal Injection of Conbercept Ophthalmic Injection in Treatment of Macular Edema Secondary to Central Retinal Vein Occlusion
Study Type
Interventional

2. Study Status

Record Verification Date
July 2022
Overall Recruitment Status
Completed
Study Start Date
May 24, 2016 (Actual)
Primary Completion Date
April 13, 2020 (Actual)
Study Completion Date
September 28, 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

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Macular Edema, Central Retinal Vein Occlusion
Keywords
Conbercept ophthalmic injection, ME, CRVO

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
Conbercept
Arm Type
Experimental
Arm Description
Conbercept
Arm Title
Conbercept or sham
Arm Type
Sham Comparator
Arm Description
Conbercept or sham
Intervention Type
Drug
Intervention Name(s)
Conbercept Ophthalmic Injection
Intervention Description
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).
Intervention Type
Drug
Intervention Name(s)
sham injection
Intervention Description
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).
Primary Outcome Measure Information:
Title
Best Corrected Visual Acuity
Description
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.
Time Frame
month 6
Secondary Outcome Measure Information:
Title
Best Corrected Visual Acuity
Description
To 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, month6 and month 12
Title
Number of subject who received laser rescue treatment
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
month 6 and month 12 or trail period
Other Pre-specified Outcome Measures:
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 change in Best Corrected Visual Acuity
Description
To evaluate mean changes in BCVA from baseline of the treatment group and the control group at every visit for 1 year.
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
Mean changes in CRT, Macular Volume
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 for 1 year
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Facility Information:
Facility Name
Beijing Friendship Hospital,Capital Medical University
City
Beijing
Country
China
Facility Name
Beijing Tongren 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 General Hospital of the People's Liberation Army
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
City
Guangzhou
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
Nanjing First Hospital
City
Nanjing
Country
China
Facility Name
The First Affiliated Hospital of Guangxi Medical University
City
Nanning
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
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
Tianjin
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
The First Affiliated Hospital of Xi'An Jiaotong University
City
Xi'an
Country
China

12. IPD Sharing Statement

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Conbercept Ophthalmic Injection for Patients of Central Retinal Vein Occlusion

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