Day Regimes of CONbercept on CytokinEs of PDR Patients Undergoing Vitrectomy - Trial (CONCEPT)

NCT ID: NCT03506750

Last Updated: 2018-04-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

UNKNOWN

Clinical Phase

PHASE4

Total Enrollment

200 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-06-03

Study Completion Date

2018-12-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

Patients with proliferative diabetic retinopathy requiring surgical intervention will receive a pre-operative injection of Conbercept. Patients will be recruited into different groups according to variable time intervals (1 to 7 days) between intravitreous injection and surgery. At initial, pre-injection aqueous humor and blood sample will be collected in order to provide baseline VEGF-A, -B, placental growth factor (PIGF), and other cytokine levels. At the onset of the vitrectomy, a second aqueous humor, blood, and vitreous sample will be taken to obtain intra-operative levels of , VEGF-A, -B, PIGF, and other cytokine levels.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Proliferative diabetic retinopathy (PDR), characterized by neovascularization and fibrous proliferation, is a severe and common complication of diabetes mellitus (DM). Persistent vitreous hemorrhage (VH) caused by neovascularization and tractional retinal detachment (TRD) caused by fibrous proliferation can lead to permanent vision loss or even blindness, which are the most common indications for surgical intervention.

As neovascularization is the basal pathophysiological change of PDR and vascular endothelial growth factor (VEGF) has been acknowledged as primary angiogenesis factor, the preoperative adjunctive use of VEGF blockade is rationally proposed. The anti-VEGF drugs have been reported to be effective in bringing about regression of retinal neovascularization, shortening surgical duration, avoiding risk of iatrogenic retinal hole and secondary operation for the recurrent VH.

Conbercept (KH902) is a newly developed anti-VEGF drug and has been applied in clinic. Because of its additional binding domain of VEGFR-2, conbercept can bind to all isoforms of VEGF-A, VEGF-B, and placental growth factor (PLGF). A number of studies have presented its high affinity in the treatment of fundus diseases such as wet age-related macular degeneration (wet-AMD), macular edema secondary to retinal vein occlusion\[8\] and diabetic retinopathy. Also, recent randomized controlled trials have shown its protective effect of conbercept for the surgical treatment of PDR.

Although the overwhelming clinical evidence supports the anti-VEGF drugs as the preoperative adjuncts for PDR, the optimal duration between anti-VEGF injection and surgical intervention has not yet reached a consensus. Longer duration is related to higher incidence of the development or progression of TRD. It might provide clues by investigation of the pattern of cytokine changes in humor aqueous, vitreous, and blood. No studies have been done to date in patients with PDR to quantify the reduction of intravitreal VEGF-A, -B, PLGF or other cytokines levels in these patients following intravitreal Conbercept injection or to evaluate the effects of VEGF or PIGF blockade on the neovascular regression and surgical outcome in patients with extensive diabetic proliferative neovascularization.

The goal of this study is to quantify the reduction of changes of VEGF-A, -B, PLGF levels in patients receiving r pre-operative intravitreal Conbercept after variable time intervals (1, 2, 3, 4, 5, 6, 7 days).

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Proliferative Diabetic Retinopathy VEGF Overexpression

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Investigators

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

IVC-1day

patients with proliferative diabetic retinopathy receiving IVC 1 days before surgery

Group Type EXPERIMENTAL

IVC

Intervention Type DRUG

Patients with PDR will receive intravitreal injection of conbercept (0.5 mg/0.05 mL; Chengdu Kanghong Biotech, Inc., Chengdu, Sichuan, China) in the inferior-temporal sector 4 mm from the sclerocorneal limbus before pars plana vitrectomy (PPV) surgery.

Blood and aqueous humor at the time of IVC

Intervention Type PROCEDURE

Initial blood and aqueous humor will be harvested at the time of IVC.

Collect blood, aqueous humor, and initial vitreous at the time of surgery.

Intervention Type PROCEDURE

Blood, aqueous humor, and vitreous will be collected at the time of surgery.

IVC-2day

patients with proliferative diabetic retinopathy receiving IVC 2 days before surgery

Group Type EXPERIMENTAL

IVC

Intervention Type DRUG

Patients with PDR will receive intravitreal injection of conbercept (0.5 mg/0.05 mL; Chengdu Kanghong Biotech, Inc., Chengdu, Sichuan, China) in the inferior-temporal sector 4 mm from the sclerocorneal limbus before pars plana vitrectomy (PPV) surgery.

Blood and aqueous humor at the time of IVC

Intervention Type PROCEDURE

Initial blood and aqueous humor will be harvested at the time of IVC.

Collect blood, aqueous humor, and initial vitreous at the time of surgery.

Intervention Type PROCEDURE

Blood, aqueous humor, and vitreous will be collected at the time of surgery.

IVC-3day

patients with proliferative diabetic retinopathy receiving IVC 3 days before surgery

Group Type EXPERIMENTAL

IVC

Intervention Type DRUG

Patients with PDR will receive intravitreal injection of conbercept (0.5 mg/0.05 mL; Chengdu Kanghong Biotech, Inc., Chengdu, Sichuan, China) in the inferior-temporal sector 4 mm from the sclerocorneal limbus before pars plana vitrectomy (PPV) surgery.

Blood and aqueous humor at the time of IVC

Intervention Type PROCEDURE

Initial blood and aqueous humor will be harvested at the time of IVC.

Collect blood, aqueous humor, and initial vitreous at the time of surgery.

Intervention Type PROCEDURE

Blood, aqueous humor, and vitreous will be collected at the time of surgery.

IVC-4day

patients with proliferative diabetic retinopathy receiving IVC 4 days before surgery

Group Type EXPERIMENTAL

IVC

Intervention Type DRUG

Patients with PDR will receive intravitreal injection of conbercept (0.5 mg/0.05 mL; Chengdu Kanghong Biotech, Inc., Chengdu, Sichuan, China) in the inferior-temporal sector 4 mm from the sclerocorneal limbus before pars plana vitrectomy (PPV) surgery.

Blood and aqueous humor at the time of IVC

Intervention Type PROCEDURE

Initial blood and aqueous humor will be harvested at the time of IVC.

Collect blood, aqueous humor, and initial vitreous at the time of surgery.

Intervention Type PROCEDURE

Blood, aqueous humor, and vitreous will be collected at the time of surgery.

IVC-5day

patients with proliferative diabetic retinopathy receiving IVC 5 days before surgery

Group Type EXPERIMENTAL

IVC

Intervention Type DRUG

Patients with PDR will receive intravitreal injection of conbercept (0.5 mg/0.05 mL; Chengdu Kanghong Biotech, Inc., Chengdu, Sichuan, China) in the inferior-temporal sector 4 mm from the sclerocorneal limbus before pars plana vitrectomy (PPV) surgery.

Blood and aqueous humor at the time of IVC

Intervention Type PROCEDURE

Initial blood and aqueous humor will be harvested at the time of IVC.

Collect blood, aqueous humor, and initial vitreous at the time of surgery.

Intervention Type PROCEDURE

Blood, aqueous humor, and vitreous will be collected at the time of surgery.

IVC-6day

patients with proliferative diabetic retinopathy receiving IVC 6 days before surgery

Group Type EXPERIMENTAL

IVC

Intervention Type DRUG

Patients with PDR will receive intravitreal injection of conbercept (0.5 mg/0.05 mL; Chengdu Kanghong Biotech, Inc., Chengdu, Sichuan, China) in the inferior-temporal sector 4 mm from the sclerocorneal limbus before pars plana vitrectomy (PPV) surgery.

Blood and aqueous humor at the time of IVC

Intervention Type PROCEDURE

Initial blood and aqueous humor will be harvested at the time of IVC.

Collect blood, aqueous humor, and initial vitreous at the time of surgery.

Intervention Type PROCEDURE

Blood, aqueous humor, and vitreous will be collected at the time of surgery.

IVC-7day

patients with proliferative diabetic retinopathy receiving IVC 7 days before surgery

Group Type EXPERIMENTAL

IVC

Intervention Type DRUG

Patients with PDR will receive intravitreal injection of conbercept (0.5 mg/0.05 mL; Chengdu Kanghong Biotech, Inc., Chengdu, Sichuan, China) in the inferior-temporal sector 4 mm from the sclerocorneal limbus before pars plana vitrectomy (PPV) surgery.

Blood and aqueous humor at the time of IVC

Intervention Type PROCEDURE

Initial blood and aqueous humor will be harvested at the time of IVC.

Collect blood, aqueous humor, and initial vitreous at the time of surgery.

Intervention Type PROCEDURE

Blood, aqueous humor, and vitreous will be collected at the time of surgery.

IVC-sham

patients with proliferative diabetic retinopathy receiving sham IVC

Group Type SHAM_COMPARATOR

Collect blood, aqueous humor, and initial vitreous at the time of surgery.

Intervention Type PROCEDURE

Blood, aqueous humor, and vitreous will be collected at the time of surgery.

IVC-sham

Intervention Type PROCEDURE

Patients with PDR will receive sham intravitreal injection of conbercept in the inferior-temporal sector 4 mm from the sclerocorneal limbus 4 days before PPV surgery.

non-DR

patients with other retinopathy (idiopathic macular hole or epiretinal membrane)

Group Type PLACEBO_COMPARATOR

Collect blood, aqueous humor, and initial vitreous at the time of surgery.

Intervention Type PROCEDURE

Blood, aqueous humor, and vitreous will be collected at the time of surgery.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

IVC

Patients with PDR will receive intravitreal injection of conbercept (0.5 mg/0.05 mL; Chengdu Kanghong Biotech, Inc., Chengdu, Sichuan, China) in the inferior-temporal sector 4 mm from the sclerocorneal limbus before pars plana vitrectomy (PPV) surgery.

Intervention Type DRUG

Blood and aqueous humor at the time of IVC

Initial blood and aqueous humor will be harvested at the time of IVC.

Intervention Type PROCEDURE

Collect blood, aqueous humor, and initial vitreous at the time of surgery.

Blood, aqueous humor, and vitreous will be collected at the time of surgery.

Intervention Type PROCEDURE

IVC-sham

Patients with PDR will receive sham intravitreal injection of conbercept in the inferior-temporal sector 4 mm from the sclerocorneal limbus 4 days before PPV surgery.

Intervention Type PROCEDURE

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* 18 years or older
* Type 1 or 2 diabetes
* PDR patients requiring surgical intervention for complications of vitreous hemorrhage or traction retinal detachment and pre-operative IVC treatment.
* women postmenopausal for 12 months before the study, surgically sterile, or not pregnant and on effective contraception.

Exclusion Criteria

* previous retinal vein occlusion.
* any intraocular surgery within the previous 12 months.
* myopia of \> or = to 8 diopters.
* active ocular or periocular infection
* treatment with an investigational agent for any condition 60 days prior to enrollment.
* evidence of severe cardiac disease.
* clinically significant peripheral vascular disease (previous surgery, amputation, or symptoms of claudication)
* uncontrolled hypertension (treated systolic blood pressure \> 155 mmHg or diastolic blood pressure \> 95 mmHg)
* stroke within the preceding 12 months.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

The First Affiliated Hospital with Nanjing Medical University

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Zizhong Hu

Dr.

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Qinghuai Liu

Role: STUDY_DIRECTOR

The First Affiliated Hospital with Nanjing Medical University

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

First Affiliated Hospital of Nanjing Medical University

Nanjing, Jiangsu, China

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

China

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Zizhong Hu, Dr

Role: CONTACT

15195960100

Ping Xie

Role: CONTACT

13915975130

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Zizhong Hu, Dr

Role: primary

15195960100

References

Explore related publications, articles, or registry entries linked to this study.

Chen DY, Sun NH, Chen X, Gong JJ, Yuan ST, Hu ZZ, Lu NN, Korbelin J, Fukunaga K, Liu QH, Lu YM, Han F. Endothelium-derived semaphorin 3G attenuates ischemic retinopathy by coordinating beta-catenin-dependent vascular remodeling. J Clin Invest. 2021 Feb 15;131(4):e135296. doi: 10.1172/JCI135296.

Reference Type DERIVED
PMID: 33586674 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

CONCEPT

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

PRP vs PRP+IVC for Severe nPDR
NCT03863535 UNKNOWN NA
DIabetic Retinopathy Candesartan Trials
NCT00252694 COMPLETED PHASE3
DIabetic Retinopathy Candesartan Trials.
NCT00252720 COMPLETED PHASE3