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

Nanjing Medical University

Status and phase: Unknown; Phase 4

Conditions: Proliferative Diabetic Retinopathy; VEGF Overexpression

Treatments: Procedure: IVC-sham; Procedure: Blood and aqueous humor at the time of IVC; Procedure: Collect blood, aqueous humor, and initial vitreous at the time of surgery.; Drug: IVC

Study type: Interventional

Funder types: Other

Identifiers

NCT03506750

CONCEPT

Details and patient eligibility

About

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.

Full 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).

Enrollment: 200 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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200 participants in 9 patient groups, including a placebo group

IVC-1day

Experimental group

Description:

patients with proliferative diabetic retinopathy receiving IVC 1 days before surgery

Treatment:

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.

IVC-2day

Experimental group

Description:

patients with proliferative diabetic retinopathy receiving IVC 2 days before surgery

Treatment:

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.

IVC-3day

Experimental group

Description:

patients with proliferative diabetic retinopathy receiving IVC 3 days before surgery

Treatment:

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.

IVC-4day

Experimental group

Description:

patients with proliferative diabetic retinopathy receiving IVC 4 days before surgery

Treatment:

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.

IVC-5day

Experimental group

Description:

patients with proliferative diabetic retinopathy receiving IVC 5 days before surgery

Treatment:

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.

IVC-6day

Experimental group

Description:

patients with proliferative diabetic retinopathy receiving IVC 6 days before surgery

Treatment:

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.

IVC-7day

Experimental group

Description:

patients with proliferative diabetic retinopathy receiving IVC 7 days before surgery

Treatment:

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.

IVC-sham

Sham Comparator group

Description:

patients with proliferative diabetic retinopathy receiving sham IVC

Treatment:

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

Procedure: IVC-sham

non-DR

Placebo Comparator group

Description:

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

Treatment:

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