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

This study has been terminated.
(Low enrollment due to the stringent enrollment criteria. Unable to answer study questions)
Sponsor:
Information provided by:
Vision Research Foundation
ClinicalTrials.gov Identifier:
NCT00702819
First received: June 19, 2008
Last updated: January 26, 2010
Last verified: June 2008
  Purpose

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.


Condition Intervention Phase
Retinopathy of Prematurity
Drug: Bevacizumab
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 1 Trial of Pan-VEGF Blockade for the Treatment of Retinopathy of Prematurity

Resource links provided by NLM:


Further study details as provided by Vision Research Foundation:

Primary Outcome Measures:
  • The primary aim is to evaluate the safety of Bevacizumab (Avastin) administered in a single dose into the vitreous cavity. [ Time Frame: Weekly ] [ Designated as safety issue: Yes ]

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. [ Time Frame: Weekly ] [ Designated as safety issue: No ]

Enrollment: 2
Study Start Date: June 2008
Study Completion Date: July 2009
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Bevacizumab
    Dosage of 0.75mg/0.03ml injectable, one time only.
    Other Name: Avastin
  Eligibility

Ages Eligible for Study:   30 Weeks to 36 Weeks
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00702819

Locations
United States, California
Jules Stein Eye Center
Los Angeles, California, United States, 90095
Childrens Hospital
Los Angeles, California, United States, 90027
California Vitreoretinal Center
Menlo Park, California, United States, 94025
United States, Florida
Bascom Palmer Eye Institute
Miami, Florida, United States, 33136
United States, Georgia
Emory Eye Center
Atlanta, Georgia, United States, 30322
United States, Massachusetts
Children's Hospital / Dept. Ophthalmology
Boston, Massachusetts, United States, 02115
United States, Michigan
William Beaumont Hospital
Royal Oak, Michigan, United States, 48073
United States, North Carolina
University of North Carolina/Ophthalmology
Chapel Hill, North Carolina, United States, 27599-7040
United States, Pennsylvania
University of Pennsylvania/Scheie Eye Institute
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
Baylor College of Medicine
Houston, Texas, United States, 77030
Canada, Alberta
Calgary Health
Calgary, Alberta, Canada, T2S-=2H4
Sponsors and Collaborators
Vision Research Foundation
Investigators
Study Chair: Michael T Trese, MD Vision Research Foundation
  More Information

Additional Information:
Publications:
Responsible Party: Michael T. Trese, MD, Vision Research Foundation
ClinicalTrials.gov Identifier: NCT00702819     History of Changes
Other Study ID Numbers: IND # 100,633, IND # 100,633
Study First Received: June 19, 2008
Last Updated: January 26, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by Vision Research Foundation:
Pan-Vascular Endothelial Growth Factor Blockade
Safety

Additional relevant MeSH terms:
Retinal Diseases
Retinopathy of Prematurity
Eye Diseases
Infant, Premature, Diseases
Infant, Newborn, Diseases
Bevacizumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 18, 2014