Clinical trial NCT03159884: The Efficacy Assessment of Intravitreal Injection of Conbercept in Patients With Polypoidal Choroidal Vasculopathy (PCV)
Official title: The Efficacy Assessment of Intravitreal Injection of Conbercept in Patients With Polypoidal Choroidal Vasculopathy (PCV)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Polypoidal Choroidal Vasculopathy (PCV)
Lead sponsor: Chengdu Kanghong Biotech Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2017-05-19
Enrollment: 300
Sex: ALL
Minimum age (years): 45
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To assess the efficacy of intravitreal injection of 0.5 mg conbercept in patients with polypoidal choroidal vasculopathy (PCV) and explore the optimal route of administration.


Eligibility criteria: Inclusion Criteria:

* Patient who has signed an informed consent form and is inclined to be followed up within the time stipulated in the trial;
* Patient with wet AMD aged ≥ 45, of either sex;
* The eye of interest must meet the following requirements:

  1. BCVA is at least 19 and at most 83 alphabets (equivalent to a visual acuity of 20/25 to 20/400 for the Snellen Eye Chart);
  2. Patient has been diagnosed with active PCV on ICGA (confirmed by the third-party radiodiagnosis center); The diagnostic criteria for "active" PCV on ICGA are as follows: image indicates polypoid lesions as typical nodular high fluorescein area (observed stereoscopically) and also depicts one of the following angiographic findings: 1) nodular lesions surrounded by the weak halo; 2) nodular lesions nourished by abnormal vascular beds; and 3) nodular pulsation on dynamic ICGA;
  3. In case of the eye of interest complicated with subretinal hemorrhage or hemorrhage under the pigment epithelium, the range of hemorrhage should not be beyond the upper and lower vascular arcades in the macular area, and the total thickness of the central fovea (i.e., the thickness between the apex of the central fovea and the choriocapillary layer) is no more than 600 µm;
  4. Neither ocular media opacity nor miosis is noted to influence the fundus examination.
* Subject with the BCVA of no less than 19 alphabets for his/her eye of non-interest (equivalent to a visual acuity of 20/400 for the Snellen Eye Chart).

Note: Each subject in the study can include only one eye of interest; the eye of interest is determined by the researcher from a medical point of view if both eyes of the subject meet the inclusion criteria.

Exclusion Criteria:

* Subfoveal fibrous tissues are present in the eye of interest on CFP and OCT;
* Researcher judges that existing or previous ocular diseases in the eye of interest influence the macular detection or the central visual acuity (CNV secondary to diseases other than AMD, diabetic retinopathy, uveitis, angioid streaks, pathologic myopia, retinal pigment epithelium (RPE) tears, macular holes, any retinal vasculopathy, vein occlusion, amblyopia, retinal inflammatory diseases, central serous choroidopathy, previous or existing retinal detachment, macular edema, anterior ischemic optic neuropathy, pseudovitelliform macular degeneration, vitreomacular traction syndrome, rhegmatogenous retinal detachment, generalized choroidal atrophy, and optic atrophy (pale));
* There is any history of vitreous hemorrhage three months before screening;
* The eye of interest has received any drug therapy for AMD (e.g., pegaptanib sodium or steroids) or any anti-VEGF therapy (e.g., ranibizumab or bevacizumab);
* The eye of interest has received verteporfin-photodynamic therapy (PDT) and foveal laser-induced thermal therapy (including subfoveal or paracentral photocoagulation, grid photocoagulation, transpupillary thermotherapy (TTT) and pan-retinal photocoagulation);
* The eye of interest has received intra- or periocular surgery (including parafoveal laser photocoagulation treatment, cataract surgery, and YAG laser posterior capsulotomy) within three months, except eyelid surgery having no effect on intravitreal injection (but eyelid surgery could not be performed one month before medication);
* The eye of interest has received the following ophthalmic operations, including vitrectomy, macular translocation, glaucoma surgery, laser photocoagulation and pan-retinal photocoagulation, as well as other submacular surgeries or other surgeries for CNV;
* The eye of interest has received keratoplasty;
* Either eye has active eye infection (e.g., blepharitis, infective conjunctivitis, keratitis, scleritis, and endophthalmitis) or recurrent infection, or the eye of interest has been infected 30 days before screening;
* Patient has either previous or existing uncontrollable glaucoma (defined as IOP remaining at above 25 mmHg after anti-glaucoma treatment), or the cup-to-disc ratio of the eye of interest is above 0.8 due to severe glaucoma, or the eye of interest has received glaucoma filtration surgery;
* No ruptured lens (excluding pseudophakic) or posterior lens capsule (except YAG laser posterior capsulotomy after intraocular lens implantation);
* Patient needs to receive cataract surgery three months after enrollment (i.e., the researcher judges that BCVA may decrease by no less than 10 alphabets for the subject if the surgery is not performed);
* The eye of interest has ocular tumor;
* There is a history of systemic use of anti-VEGF agent(s) in six months;
* Patient has a history of anaphylaxis and allergy to fluorescein sodium and indocyanine green, 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;
* Diabetics with uncontrolled blood glucose (fasting blood glucose ≥ 7.0 mmol/L or 2hPBG ≥ 11.1 mmol/L) and/or complicated with diabetic retinopathy;
* Patient has had a surgical history one month before enrollment, and/or has unhealed wounds, ulcers and fractures at present;
* Patient has infectious diseases required oral, intramuscular or intravenous administration at present;
* Patient has a history of myocardial and/or cerebral infarction(s) within 6 months before screening, has received stenting and depends on such anticoagulants as warfarin and aspirin;
* Patient chronically uses and cannot discontinue to use such anticoagulants as aspirin, clopidogrel and warfarin;
* Patient has active and disseminated intravascular coagulation and distinct bleeding tendency three months before screening;
* Hyperpietics with poor blood pressure control (defined as blood pressure remaining at ≥ 150/95 mmHg after antihypertensives therapy);
* Patient is diagnosed with systemic immune disease (e.g., ankylosing spondylitis, systemic lupus erythematosus, and Behcet's disease) or has any uncontrollable clinical problem (e.g., AIDS, malignancies, active hepatitis, renal failure, severe mental, neurological, cardiovascular and respiratory diseases);
* Patient has previously used drugs which may possibly cause renal toxicity, including chloroquine, hydroxychloroquine, phenothiazines, chlorpromazine, thioridazine, fluphenazine, perphenazine, and trifluoperazine;
* Patient does not take effective contraceptive measures; 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 (in this trial pregnancy is defined as positive U-HCG) and breastfeeding mothers;
* 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); Those whom the reseacher deems necessary to exclude.

Primary outcomes:
measure: Change of Best Corrected Visual Acuity
timeFrame: Baseline, 12th and 48th week
Secondary outcomes:
measure: Central Retinal Thickness (CRT)
timeFrame: week 48
measure: Change of Macular Retinal Thickness (MRT)
timeFrame: week 48
measure: Volume and Thickness of Retinal Pigment Epithelial Detachment (PED)
timeFrame: week 48
measure: Area and Regression of Polypoidal Lesion
timeFrame: week 48
measure: Size of Retinal Hemorrhages
timeFrame: week 48
measure: Area of Branching Vascular Network
timeFrame: week 48
measure: Frequency of Administration
timeFrame: up to 48 weeks
measure: Incidence of adverse events (AEs) and reactions
timeFrame: up to 48 weeks
measure: Ophthalmic examination
timeFrame: up to 48 weeks
measure: General symptoms and vital signs
timeFrame: up to 48 weeks
measure: Number of participants with adverse events as assessed by laboratory results
timeFrame: up to 48 weeks
measure: Number of participants with treatment-related adverse events as assessed by other tests.
timeFrame: up to 48 weeks.
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Hospital
city: Beijing
country: China
facility: Beijing Shijitan Hoospital.Cmu
city: Beijing
country: China
facility: Beijing Tongren Hospital,Cmu
city: Beijing
country: China
facility: Chinese Pla General Hospital
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: Changsha
country: China
facility: The Scond Xiangya Hospital of Central South University
city: Changsha
country: China
facility: Xiangya Hospital Central South University
city: Guangzhou
country: China
facility: General Hospial og Guangzhou Military Command of PLA
city: Guangzhou
country: China
facility: ZhongShan Ophthalmic Center,Sun Yat-sen University
city: Hainan
country: China
facility: Hainan Eye Hospital of Zhongshan Ophthalmic Center, Sun Yat-sen University
city: Hebei
country: China
facility: Hebei Eye Hospital
city: Hebei
country: China
facility: The Second Hospital of Hebei Medical University
city: Henan
country: China
facility: Henan Province People's Hospital
city: Jilin
country: China
facility: The Second Hospital of Jilin University
city: Lanzhou
country: China
facility: Lanzhou University Second Hospital
city: Nanchang
country: China
facility: Affiliated Eye Hospital of Nanchang University
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
city: Nanjing
country: China
facility: Nanjing General Hospital
city: Nanjing
country: China
facility: The First Affiliated Hospital With Nanjing Medical University
city: Ningxia
country: China
facility: Ningxia Peple'S Hospital
city: Shanghai
country: China
facility: Eye&Ent Hospital of Fudan University
city: Shanghai
country: China
facility: Renji Hospital Shanghai Jiaotong University School of Medicine
city: Shanghai
country: China
facility: Shanghai General Hospital
city: Shantou
country: China
facility: Stu/Cuhk Joint Shantou International Eye Center
city: Shanxi
country: China
facility: Shanxi Eye Hospital
city: Shenzhen
country: China
facility: Shenzhen Eye Hospital
city: Tianjin
country: China
facility: Tianjin Medical University Eye Hospital
city: Wenzhou
country: China
facility: The Eye Hospital of Wmu Zhejiang Eye Hospital
city: Wuhan
country: China
facility: Renmin Hospital of Wuhan University
city: Wulumuqi
country: China
facility: The Chinese people's liberation army 474 hospital
city: Xiamen
country: China
facility: Xiamen Eye Centre of Xiamen University
city: Zhejiang
country: China
facility: The Second Affiliated Hospital Zhejiang University School of Medicine
Study officials:
References: