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

Proliferative Diabetic Retinopathy Clinical Trial

— CONCEPT  

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03506750
• Other study ID #: CONCEPT
• Status: Recruiting
• Phase: Phase 4
• First received: March 9, 2018
• Last updated: April 12, 2018
• Start date: June 3, 2017
• Est. completion date: December 31, 2018

Study information

• Verified date: April 2018
• Source: The First Affiliated Hospital with Nanjing Medical University
• Contact: Zizhong Hu, Dr
• Phone: 15195960100
• Email: huzizhong[@]njmu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: December 31, 2018
• Est. primary completion date: September 1, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Diabetic Retinopathy
• Proliferative Diabetic Retinopathy
• Retinal Diseases
• VEGF Overexpression

Intervention

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.
• 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.
• 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.

Locations

Country	Name	City	State
China	First Affiliated Hospital of Nanjing Medical University	Nanjing	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
The First Affiliated Hospital with Nanjing Medical University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes of intraocular VEGF and PLGF of patients with proliferative diabetic retinopathy post-IVC (intravitreous injection of Conbercept).		1-7 days
Secondary	Changes of serum angiogenesis-related pro-cytokines in patients with proliferative diabetic retinopathy		1-7 days
Secondary	Changes of intraocular and serum pro?brotic cytokines in patients with proliferative diabetic retinopathy post-IVC.		1-7 days
Secondary	Changes of intraocular and serum inflammatory cytokines in patients with proliferative diabetic retinopathy post-IVC.		1-7 days
Secondary	Vitreous concentration of Conbercept	Detection of Vitreous concentration of the drug of Conbercept (Conbercept is a kind of fusion protein)	1-7 days
Secondary	Effect of IVC on surgery time of surgery	surgery time of vitrectomy	Surgery day
Secondary	Effect of IVC on intraoperative complication of surgery	Record the intraoperative complication: bleeding and iatrogenic retinal hole when surgically removing the proliferative membranes.	Surgery day
Secondary	Effect of IVC on regression of neovascularization on vitreous fibrovascular membrane with optic coherence tomography angiography (OCTA)	OCTA monitor the changes of neovascularization on vitreous fibrovascular membrane after IVC and before surgery	1 to 7 days
Secondary	Effect of IVC on postoperative visual acuity	Best-corrected visual acuity postoperatively	1 to12 months
Secondary	Effect of IVC on postoperative complications	Record number of patient with vitreous re-bleeding and iris neovascularization postoperatively.	1 to12 months