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

Retinopathy of Prematurity Clinical Trial

— BLOCK-ROP  

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01232777
• Other study ID #: 002
• Status: Withdrawn
• Phase: Phase 2
• First received: October 26, 2010
• Last updated: October 16, 2013
• Start date: June 2012
• Est. completion date: July 2018

Study information

• Verified date: October 2013
• 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

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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: July 2018
• Est. primary completion date: April 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 30 Weeks to 36 Weeks

Eligibility

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)

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Premature Birth
• Retinal Diseases
• Retinopathy of Prematurity

Intervention

Drug:
• Bevacizumab
A single dosage of: 0.625mg(0.025cc)or 0.75mg(0.03cc) will be given intravitreally.

Locations

Country	Name	City	State
Canada	Ells Retina Centre	Calgary	Alberta
United States	Emory Eye Center	Atlanta	Georgia
United States	Austin Retina Associates	Austin	Texas
United States	Children's Hospital, Dept. of Ophthalmology	Boston	Massachusetts
United States	Abrahamson Pediatric Eye Institute, Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Cleveland Clinic	Cleveland	Ohio
United States	Midwest Retina	Dublin	Ohio
United States	Texas Children's Hospital	Houston	Texas
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	Jules Stein Eye Institute, UCLA	Los Angeles	California
United States	University Hospitals Eye Insitute, Rainbow Babies & Children's Hospital	Mayfield Heights	Ohio
United States	Bascon Palmer Eye Institute	Miami	Florida
United States	Medical College of Wisconsin--Eye Insititute	Milwaukee	Wisconsin
United States	Department of Ophthalmology, Weill Cornell Medical College	New York	New York
United States	Insitute of Ophthalmology and Medical Science, New Jersey Medical School	Newark	New Jersey
United States	Eye Insitute at Stanford	Palo Alto	California
United States	St. Christopher's Hospital for Children, Drexel Univ. School of Medicine	Philadelphia	Pennsylvania
United States	Associated Retinal Consultants/William Beaumont Hospital	Royal Oak	Michigan
United States	University of Utah, Moran Eye Center	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Vision Research Foundation

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To demonstrate non-inferiority of Anti-VEGF treatment to standard-of-care laser	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.	With patient #58, 116 and 174 (within 3 months after each patient being enrolled)	Yes
Secondary	Decreased laser ablation and improved vascular maturity	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.	With patient #58, 116 & 174 (within 3 months after each patient being enrolled)	No