Clinical trial NCT03506750: Day Regimes of CONbercept on CytokinEs of PDR Patients Undergoing Vitrectomy - 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)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Proliferative Diabetic Retinopathy
VEGF Overexpression
Keywords: Conbercept
PLGF
Lead sponsor: The First Affiliated Hospital with Nanjing Medical University
Sponsor class: OTHER
First posted: 2018-04-24
Enrollment: 200
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: 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: 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).

Eligibility 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.

Primary outcomes:
measure: Changes of intraocular VEGF and PLGF of patients with proliferative diabetic retinopathy post-IVC (intravitreous injection of Conbercept).
timeFrame: 1-7 days
Secondary outcomes:
measure: Changes of serum angiogenesis-related pro-cytokines in patients with proliferative diabetic retinopathy
timeFrame: 1-7 days
measure: Changes of intraocular and serum proﬁbrotic cytokines in patients with proliferative diabetic retinopathy post-IVC.
timeFrame: 1-7 days
measure: Changes of intraocular and serum inflammatory cytokines in patients with proliferative diabetic retinopathy post-IVC.
timeFrame: 1-7 days
measure: Vitreous concentration of Conbercept
timeFrame: 1-7 days
measure: Effect of IVC on surgery time of surgery
timeFrame: Surgery day
measure: Effect of IVC on intraoperative complication of surgery
timeFrame: Surgery day
measure: Effect of IVC on regression of neovascularization on vitreous fibrovascular membrane with optic coherence tomography angiography (OCTA)
timeFrame: 1 to 7 days
measure: Effect of IVC on postoperative visual acuity
timeFrame: 1 to12 months
measure: Effect of IVC on postoperative complications
timeFrame: 1 to12 months
Other outcomes:
Locations:
city: Nanjing
country: China
facility: First Affiliated Hospital of Nanjing Medical University
state: Jiangsu
Study officials:
affiliation: The First Affiliated Hospital with Nanjing Medical University
name: Qinghuai Liu
role: STUDY_DIRECTOR
References:
citation: 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.