Clinical trial NCT03108352: Conbercept Ophthalmic Injection for Patients With Macular Edema Caused by Branch Retinal Vein Occlusion
Official title: Multi-center, Randomized, Double-masked, Placebo-controlled Phase III Clinical Study of Conbercept Ophthalmic Injection for Patients With BRVO.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Branch Retinal Vein Occlusion
Macular Edema
Lead sponsor: Chengdu Kanghong Biotech Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2017-04-11
Enrollment: 255
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


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:

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.

Primary outcomes:
measure: Best Corrected Visual Acuity
timeFrame: month 6
Secondary outcomes:
measure: Best Corrected Visual Acuity (BCVA)
timeFrame: month 3 and month 12
measure: Central Retinal Thickness
timeFrame: month 3, month 6 and month 12
measure: resue treament
timeFrame: month 6 and month 12
measure: Number of participants with treatment-related the systemic and ocular safely as assessed
timeFrame: up to 12.5 months
measure: distribution of BCVA changes
timeFrame: month 3, month 6 and month 12
measure: mean changes in BCVA
timeFrame: 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
measure: Change in image
timeFrame: 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 outcomes:
measure: Immunogenic positive response in the treatment group
timeFrame: baseline,month 6, month 12
measure: Immunogenic positive response in the control group
timeFrame: baseline,month 6, month 12
measure: safety analysis of immunogenic positive response
timeFrame: month 12
measure: safety analysis of immunogenic negative response
timeFrame: month 12
measure: Best Corrected Visual Acuity (BCVA)
timeFrame: month 12
Locations:
city: Beijing
country: China
facility: The General Hospital of the People's Liberation Army
state: Beijing
city: Beijing
country: China
facility: Beijing Friendship Hospital, Capital Medical University
city: Beijing
country: China
facility: Peking Union Medical College Hospital
city: Beijing
country: China
facility: Peking University First Hospital
city: Beijing
country: China
facility: Peking University People's Hospital
city: Beijing
country: China
facility: Peking University Third Hospital
city: Changchun
country: China
facility: The Second Hospital of Jilin University
city: Changsha
country: China
facility: The Second Xiangya Hospital of Central South University
city: Chengdu
country: China
facility: West China Hospital Sichuan University
city: Chongqing
country: China
facility: Army Medical Center
city: Dalian
country: China
facility: The Second Hospital of Dalian Medical University
city: Guangzhou
country: China
facility: Zhongshan Ophthalmic Center, Sun Yat-Sen University
city: Hangzhou
country: China
facility: The Second Affiliated Hospital Zhejiang University School of Medicine
city: Harbin
country: China
facility: The 2nd Affiliated Hospital of Harbin Medical University
city: Nanchang
country: China
facility: The Jiangxi Provincial People's Hospital
city: Nanjing
country: China
facility: Jiangsu Province Hospital
city: Nanjing
country: China
facility: Nanjing First Hospital
city: Nanning
country: China
facility: The First Affiliated Hospital of Guangxi Medical University
city: Peking
country: China
facility: Beijing Tongren Hospital, Capital Medical University
city: Shanghai
country: China
facility: Eye & Ent Hospital of Fudan University
city: Shanghai
country: China
facility: Shanghai General Hospital
city: Shanghai
country: China
facility: Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
city: Shanghai
country: China
facility: Zhongshan Hospital
city: Shenyang
country: China
facility: The First Hospital of China Medical University
city: Tianjing
country: China
facility: Tianjin Eye Hospital
city: Tianjin
country: China
facility: Tianjin Medical University Eye Hospital School of Optometry & Eye Institute
city: Urumqi
country: China
facility: The First Affiliated Hospital of Xinjiang Medical University
city: Wenzhou
country: China
facility: Eye Hospital,WMU Zhejiang Eye Hospital
city: Wuhan
country: China
facility: Wuhan General Hospital of Guangzhou Military Command
city: Wuxi
country: China
facility: Wuxi No.2 People's Hospital
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xi'An
Study officials:
References:
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.