Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03506750
Recruitment Status : Recruiting
First Posted : April 24, 2018
Last Update Posted : April 24, 2018
Sponsor:
Information provided by (Responsible Party):
Zizhong Hu, The First Affiliated Hospital with Nanjing Medical University

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Proliferative Diabetic Retinopathy VEGF Overexpression Drug: IVC Procedure: Blood and aqueous humor at the time of IVC Procedure: Collect blood, aqueous humor, and initial vitreous at the time of surgery. Procedure: IVC-sham Phase 4

Detailed Description:

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).


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Investigator)
Primary Purpose: Treatment
Official Title: Different Day Regimes of Preoperative CONbercept Administration on CytokinEs of Proliferative Diabetic Retinopathy Patients Undergoing Vitrectomy: a Prospective Randomized Controlled Clinical Trial (CONCEPT)
Actual Study Start Date : June 3, 2017
Estimated Primary Completion Date : September 1, 2018
Estimated Study Completion Date : December 31, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: IVC-1day
patients with proliferative diabetic retinopathy receiving IVC 1 days before surgery
Drug: 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.

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

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.

Experimental: IVC-2day
patients with proliferative diabetic retinopathy receiving IVC 2 days before surgery
Drug: 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.

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

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.

Experimental: IVC-3day
patients with proliferative diabetic retinopathy receiving IVC 3 days before surgery
Drug: 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.

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

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.

Experimental: IVC-4day
patients with proliferative diabetic retinopathy receiving IVC 4 days before surgery
Drug: 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.

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

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.

Experimental: IVC-5day
patients with proliferative diabetic retinopathy receiving IVC 5 days before surgery
Drug: 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.

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

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.

Experimental: IVC-6day
patients with proliferative diabetic retinopathy receiving IVC 6 days before surgery
Drug: 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.

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

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.

Experimental: IVC-7day
patients with proliferative diabetic retinopathy receiving IVC 7 days before surgery
Drug: 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.

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

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.

Sham Comparator: IVC-sham
patients with proliferative diabetic retinopathy receiving sham IVC
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.

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.

Placebo Comparator: non-DR
patients with other retinopathy (idiopathic macular hole or epiretinal membrane)
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.




Primary Outcome Measures :
  1. Changes of intraocular VEGF and PLGF of patients with proliferative diabetic retinopathy post-IVC (intravitreous injection of Conbercept). [ Time Frame: 1-7 days ]

Secondary Outcome Measures :
  1. Changes of serum angiogenesis-related pro-cytokines in patients with proliferative diabetic retinopathy [ Time Frame: 1-7 days ]
  2. Changes of intraocular and serum profibrotic cytokines in patients with proliferative diabetic retinopathy post-IVC. [ Time Frame: 1-7 days ]
  3. Changes of intraocular and serum inflammatory cytokines in patients with proliferative diabetic retinopathy post-IVC. [ Time Frame: 1-7 days ]
  4. Vitreous concentration of Conbercept [ Time Frame: 1-7 days ]
    Detection of Vitreous concentration of the drug of Conbercept (Conbercept is a kind of fusion protein)

  5. Effect of IVC on surgery time of surgery [ Time Frame: Surgery day ]
    surgery time of vitrectomy

  6. Effect of IVC on intraoperative complication of surgery [ Time Frame: Surgery day ]
    Record the intraoperative complication: bleeding and iatrogenic retinal hole when surgically removing the proliferative membranes.

  7. Effect of IVC on regression of neovascularization on vitreous fibrovascular membrane with optic coherence tomography angiography (OCTA) [ Time Frame: 1 to 7 days ]
    OCTA monitor the changes of neovascularization on vitreous fibrovascular membrane after IVC and before surgery

  8. Effect of IVC on postoperative visual acuity [ Time Frame: 1 to12 months ]
    Best-corrected visual acuity postoperatively

  9. Effect of IVC on postoperative complications [ Time Frame: 1 to12 months ]
    Record number of patient with vitreous re-bleeding and iris neovascularization postoperatively.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03506750


Contacts
Layout table for location contacts
Contact: Zizhong Hu, Dr 15195960100 huzizhong@njmu.edu.cn
Contact: Ping Xie 13915975130 xieping9@126.com

Locations
Layout table for location information
China, Jiangsu
First Affiliated Hospital of Nanjing Medical University Recruiting
Nanjing, Jiangsu, China, 210029
Contact: Zizhong Hu, Dr    15195960100    huzizhong@njmu.edu.cn   
Sponsors and Collaborators
The First Affiliated Hospital with Nanjing Medical University
Investigators
Layout table for investigator information
Study Director: Qinghuai Liu The First Affiliated Hospital with Nanjing Medical University

Layout table for additonal information
Responsible Party: Zizhong Hu, Dr., The First Affiliated Hospital with Nanjing Medical University
ClinicalTrials.gov Identifier: NCT03506750     History of Changes
Other Study ID Numbers: CONCEPT
First Posted: April 24, 2018    Key Record Dates
Last Update Posted: April 24, 2018
Last Verified: April 2018

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Zizhong Hu, The First Affiliated Hospital with Nanjing Medical University:
Conbercept
PLGF

Additional relevant MeSH terms:
Layout table for MeSH terms
Retinal Diseases
Diabetic Retinopathy
Eye Diseases
Diabetic Angiopathies
Vascular Diseases
Cardiovascular Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases