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

This study has been withdrawn prior to enrollment.
(Lack of funding)
Sponsor:
Information provided by (Responsible Party):
Michael T. Trese, M.D., Vision Research Foundation
ClinicalTrials.gov Identifier:
NCT01232777
First received: October 26, 2010
Last updated: October 16, 2013
Last verified: October 2013
  Purpose

The purpose of this study is to determine whether a single intravitreal (into the gel of the eye) injection of Avastin 0.625mg or 0.75mg is equivalent (non-inferior) to treatment with standard of care laser in infants with Type I pre-threshold retinopathy of prematurity (ROP) diagnosed at 30-36 weeks gestational age.


Condition Intervention Phase
Retinopathy of Prematurity
Drug: Bevacizumab
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pan-VEGF Blockade for the Treatment of Retinopathy of Prematurity (BLOCK-ROP)

Resource links provided by NLM:


Further study details as provided by Vision Research Foundation:

Primary Outcome Measures:
  • To demonstrate non-inferiority of Anti-VEGF treatment to standard-of-care laser [ Time Frame: With patient #58, 116 and 174 (within 3 months after each patient being enrolled) ] [ Designated as safety issue: Yes ]
    It is the intent of this clinical study to develop alternative therapy (a single bevacizumab injection) to standard therapy (laser ablation) and to show that bevacizumab is as safe and efficacious as laser.


Secondary Outcome Measures:
  • Decreased laser ablation and improved vascular maturity [ Time Frame: With patient #58, 116 & 174 (within 3 months after each patient being enrolled) ] [ Designated as safety issue: No ]
    These 2 end-points will be monitored by evidence of persistent disease and presence/absence of progression to retinal detachment. If either or both of these objectives are not met, it is indicative of failure of treatment.


Enrollment: 0
Study Start Date: June 2012
Estimated Study Completion Date: July 2018
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Bevacizumab (Avastin) 0.75mg/0.03cc
1/3 of study participants will be randomized to this treatment in one eye (study eye) and the other eye will receive laser (fellow eye)
Drug: Bevacizumab
A single dosage of: 0.625mg(0.025cc)or 0.75mg(0.03cc) will be given intravitreally.
Other Name: Avastin
Active Comparator: Bevacizumab (Avastin) 0.625mg/0.025cc
1/3 of patients will be randomized to this treatment in 1 eye (study eye) and the other eye will receive laser (fellow eye).
Drug: Bevacizumab
A single dosage of: 0.625mg(0.025cc)or 0.75mg(0.03cc) will be given intravitreally.
Other Name: Avastin
Active Comparator: Laser ablation
1/3 of study participants will be randomized to this treatment in both eyes (study eye and fellow eye)
Drug: Bevacizumab
A single dosage of: 0.625mg(0.025cc)or 0.75mg(0.03cc) will be given intravitreally.
Other Name: Avastin

Detailed Description:

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 grow 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 multi-center 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 amendable 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 sick neonates. In this subset of infants, progression of ROP to retinal detachments in both eyes and even blindness may occur despite timely and complete peripheral retinal laser ablation.

RATIONALE:

The development of ROP is largely dependant on vascular endothelial growth factor (VEGF). When an infant is born prematurely, the relatively hyperoxic environment that the baby is introduced to shuts down the production of VEGF. Retinal maturation is thus delayed. Subsequently, at a time when intraocular VEGF levels would 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 eye off-label. Available drugs include pegaptanib sodium (Macugen) for partial blockage of VEGF-A, or drugs such a 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, we 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.

  Eligibility

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

Inclusion Criteria:

  • Inborn babies at participating NICU's who meet inclusion criteria
  • Outborn babies transferred to participating NICU's who meet inclusion criteria
  • Type 1 pre-threshold ROP
  • No prior treatment
  • Post menstrual age less than 36 1/7 weeks
  • Post menstrual age greater than 30 weeks

Exclusion Criteria:

  • Fatal systemic anomaly
  • An ocular anomaly of one or both eye affecting the retina or choroid
  • An ocular anomaly precluding use of the RetCam (ex., microphthalmia)
  • Neonatologist feels inclusion will unduly challenge the infant
  • Refusal of initial consent
  • Refusal of subsequent evaluation
  • Media opacity precluding fundus visualization (ex., 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: NCT01232777

Locations
United States, California
Jules Stein Eye Institute, UCLA
Los Angeles, California, United States, 90095
Children's Hospital Los Angeles
Los Angeles, California, United States, 90027
Eye Insitute at Stanford
Palo Alto, California, United States, 94303
United States, Florida
Bascon 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. of Ophthalmology
Boston, Massachusetts, United States, 02115
United States, Michigan
Associated Retinal Consultants/William Beaumont Hospital
Royal Oak, Michigan, United States, 48073
United States, New Jersey
Insitute of Ophthalmology and Medical Science, New Jersey Medical School
Newark, New Jersey, United States, 07103
United States, New York
Department of Ophthalmology, Weill Cornell Medical College
New York, New York, United States, 10021
United States, Ohio
Abrahamson Pediatric Eye Institute, Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
Cleveland Clinic
Cleveland, Ohio, United States, 44105
Midwest Retina
Dublin, Ohio, United States, 43016
University Hospitals Eye Insitute, Rainbow Babies & Children's Hospital
Mayfield Heights, Ohio, United States, 44134
United States, Pennsylvania
St. Christopher's Hospital for Children, Drexel Univ. School of Medicine
Philadelphia, Pennsylvania, United States, 19134
United States, Texas
Austin Retina Associates
Austin, Texas, United States, 78705
Texas Children's Hospital
Houston, Texas, United States, 77030
United States, Utah
University of Utah, Moran Eye Center
Salt Lake City, Utah, United States, 84132
United States, Wisconsin
Medical College of Wisconsin--Eye Insititute
Milwaukee, Wisconsin, United States, 53266
Canada, Alberta
Ells Retina Centre
Calgary, Alberta, Canada, T2T 5R6
Sponsors and Collaborators
Vision Research Foundation
Investigators
Principal Investigator: Michael T Trese, MD Vision Research Foundation
  More Information

No publications provided

Responsible Party: Michael T. Trese, M.D., VitreoRetinal Surgeon & Researcher, Vision Research Foundation
ClinicalTrials.gov Identifier: NCT01232777     History of Changes
Other Study ID Numbers: 002
Study First Received: October 26, 2010
Last Updated: October 16, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Vision Research Foundation:
Retinopathy of Prematurity
Bevacizumab
Avastin
Vascular Endothelial Growth Factor

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 20, 2014