Pan-VEGF Blockade for the Treatment of Retinopathy of Prematurity

Retinopathy of Prematurity Clinical Trial

— BLOCK-ROP  

Official title:

Phase 1 Trial of Pan-VEGF Blockade for the Treatment of Retinopathy of Prematurity

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00702819
• Other study ID #: IND # 100,633
• Secondary ID: IND # 100,633
• Status: Terminated
• Phase: Phase 1
• First received: June 19, 2008
• Last updated: January 26, 2010
• Start date: June 2008
• Est. completion date: July 2009

Study information

• Verified date: June 2008
• Source: Vision Research Foundation
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Retinopathy of Prematurity (ROP) is a leading cause of blindness in children in developed countries around the world, and an increasing cause of blindness in developing countries.

The retina lines the inside of the eye. It functions as "film" within the camera which is the eye. When an infant is born prematurely, the vascular network necessary to nourish the retina has not fully developed. As a consequence, in some infants abnormal vessels proliferate instead of the normal ones - a condition known as ROP. The abnormal vessels carry scar tissue along with them, and may lead to retinal detachment and blindness if the eye is not treated.

The Multicenter Trial of Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) Study demonstrated that ablation of the peripheral avascular retina reduced the risk of poor structural and visual outcome due to retinal distortion or detachment in ROP (1980's). The ablated retina is not functional and is not amenable to regeneration.

Peripheral retinal ablation is not universally effective in fostering regression of ROP. This is particularly true for an aggressive form of ROP (aggressive posterior ROP, or APROP) which typically afflicts profoundly premature and infirm neonates. In this subset of infants, progression of ROP to bilateral retinal detachment and blindness occurs despite timely and complete peripheral retinal laser ablation.

Rationale The development of ROP is largely dependent on vascular endothelial growth factor (VEGF). When an infant is born prematurely the relatively hyperoxic environment the baby is introduced to shuts down the production of VEGF. Retinal maturation is delayed. Subsequently, at a time when intraocular VEGF levels would normally be declining late in the third trimester of pregnancy, abnormally high levels of VEGF are seen due to large areas of avascular retina and associated tissue hypoxia.

The availability of FDA-approved drugs for anti-VEGF treatment renders it possible to treat such eyes off-label. Available drugs include pegaptanib sodium (Macugen) for partial blockage of VEGF-A, or drugs such as ranibizumab (Lucentis) and bevacizumab (Avastin), which cause complete blockage of VEGF-A.

As VEGF is required in the developing retina for normal angiogenesis, and our goal is not to penetrate tissue, but to block the excessive levels of VEGF trapped within the overlying vitreous which is responsible for the abnormal vasculature in ROP.

For purposes of this study the investigators have chosen bevacizumab (Avastin), which will:

a) attain complete blockage (vs. Macugen) of intravitreal VEGF-A, and; b) which is limited in its ability to penetrate tissues because it is a full antibody (vs. Lucentis, an antibody fragment specifically designed for better tissue penetration), and is more likely to restore VEGF homeostasis within the developing retina.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 2
• Est. completion date: July 2009
• Est. primary completion date: June 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 30 Weeks to 36 Weeks

Eligibility

Eligibility criteria

• Premature newborn infants with bilateral progressive APROP despite complete peripheral retinal ablation.

Inclusion Criteria:

• Inborn babies at participating NICUs (must meet inclusion criteria 3 through 7)

• Outborn babies transferred to participating NICU (must meet inclusion criteria 3 through 7)

• Aggressive posterior ROP

• Adequate/appropriate laser ablation

• Failed standard laser treatment (persistent Plus or recurrent Plus at a minimum of 1 week post-laser)

• Post-menstrual age less than 36 weeks

• Post-menstrual age greater than 30 weeks

Exclusion Criteria:

• Fatal systemic anomaly

• An ocular anomaly of one or both eyes affecting the retina or choroid

• An ocular anomaly precluding use of the RetCam (eg: microphthalmia)

• Neonatologist feels inclusion will unduly challenge the infant

• Refusal of initial consent

• Refusal of subsequent evaluation

• Media opacity precluding fundus visualization (eg: cataract)

• Any ocular or periocular infection(s)

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Premature Birth
• Retinal Diseases
• Retinopathy of Prematurity

Intervention

Drug:
• Bevacizumab
Dosage of 0.75mg/0.03ml injectable, one time only.

Locations

Country	Name	City	State
Canada	Calgary Health	Calgary	Alberta
United States	Emory Eye Center	Atlanta	Georgia
United States	Children's Hospital / Dept. Ophthalmology	Boston	Massachusetts
United States	University of North Carolina/Ophthalmology	Chapel Hill	North Carolina
United States	Baylor College of Medicine	Houston	Texas
United States	Childrens Hospital	Los Angeles	California
United States	Jules Stein Eye Center	Los Angeles	California
United States	California Vitreoretinal Center	Menlo Park	California
United States	Bascom Palmer Eye Institute	Miami	Florida
United States	University of Pennsylvania/Scheie Eye Institute	Philadelphia	Pennsylvania
United States	William Beaumont Hospital	Royal Oak	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
Vision Research Foundation

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (1)

Bakri SJ, Snyder MR, Pulido JS, McCannel CA, Weiss WT, Singh RJ. Six-month stability of bevacizumab (Avastin) binding to vascular endothelial growth factor after withdrawal into a syringe and refrigeration or freezing. Retina. 2006 May-Jun;26(5):519-22. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary aim is to evaluate the safety of Bevacizumab (Avastin) administered in a single dose into the vitreous cavity.		Weekly	Yes
Secondary	The secondary therapeutic study aim is to determine the efficacy of treatment with Bevacizumab (Avastin) for improving structural outcome without surgical intervention.		Weekly	No