Pan-VEGF Blockade for the Treatment of Retinopathy of Prematurity

NCT ID: NCT00702819

Last Updated: 2010-01-27

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 2 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-06-30
• Study Completion Date: 2009-07-31

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: 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.

Conditions

Retinopathy of Prematurity

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

Bevacizumab

Dosage of 0.75mg/0.03ml injectable, one time only.

Intervention Type: DRUG

Other Intervention Names

Avastin

Eligibility Criteria

Inclusion Criteria

• 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)

• Minimum Eligible Age: 30 Weeks
• Maximum Eligible Age: 36 Weeks
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Vision Research Foundation

OTHER

Sponsor Role: lead

Responsible Party

Vision Research Foundation

Principal Investigators

Michael T Trese, MD

Role: STUDY_CHAIR

Vision Research Foundation

Locations

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

Emory Eye Center

Atlanta, Georgia, United States

Children's Hospital / Dept. Ophthalmology

Boston, Massachusetts, United States

William Beaumont Hospital

Royal Oak, Michigan, United States

University of North Carolina/Ophthalmology

Chapel Hill, North Carolina, United States

University of Pennsylvania/Scheie Eye Institute

Philadelphia, Pennsylvania, United States

Baylor College of Medicine

Houston, Texas, United States

Calgary Health

Calgary, Alberta, Canada

Countries

United States; Canada

References

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. doi: 10.1097/01.iae.0000225354.92444.7a.

Reference Type: BACKGROUND

PMID: 16770257 (View on PubMed)

Other Identifiers

IND # 100,633

Identifier Type: -

Identifier Source: secondary_id

IND # 100,633

Identifier Type: -

Identifier Source: org_study_id