BLOCK-ROP: Pan-VEGF Blockade for the Treatment of Retinopathy of Prematurity

Sponsor

Vision Research Foundation (Other)

Overall Status

Terminated

CT.gov ID

NCT00702819

Collaborator

(none)

Enrollment

Locations

Duration (Months)

0.2

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief 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:

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.

Condition or Disease	Intervention/Treatment	Phase
Retinopathy of Prematurity	Drug: Bevacizumab	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

2 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jun 1, 2008

Actual Primary Completion Date :

Jun 1, 2009

Actual Study Completion Date :

Jul 1, 2009

Outcome Measures

Primary Outcome Measures

The primary aim is to evaluate the safety of Bevacizumab (Avastin) administered in a single dose into the vitreous cavity. [Weekly]

Secondary Outcome Measures

The secondary therapeutic study aim is to determine the efficacy of treatment with Bevacizumab (Avastin) for improving structural outcome without surgical intervention. [Weekly]

Eligibility Criteria

Criteria

Ages Eligible for Study:

30 Weeks to 36 Weeks

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Childrens Hospital	Los Angeles	California	United States	90027
2	Jules Stein Eye Center	Los Angeles	California	United States	90095
3	California Vitreoretinal Center	Menlo Park	California	United States	94025
4	Bascom Palmer Eye Institute	Miami	Florida	United States	33136
5	Emory Eye Center	Atlanta	Georgia	United States	30322
6	Children's Hospital / Dept. Ophthalmology	Boston	Massachusetts	United States	02115
7	William Beaumont Hospital	Royal Oak	Michigan	United States	48073
8	University of North Carolina/Ophthalmology	Chapel Hill	North Carolina	United States	27599-7040
9	University of Pennsylvania/Scheie Eye Institute	Philadelphia	Pennsylvania	United States	19104
10	Baylor College of Medicine	Houston	Texas	United States	77030
11	Calgary Health	Calgary	Alberta	Canada	T2S-=2H4