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

Vision Research Foundation

Status and phase: Withdrawn; Phase 2

Conditions: Retinopathy of Prematurity

Treatments: Drug: Bevacizumab

Study type: Interventional

Funder types: Other

Identifiers

NCT01232777

002

Details and patient eligibility

About

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.

Full 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.

Sex: All

Ages: 30 to 36 weeks old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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0 participants in 3 patient groups

Bevacizumab (Avastin) 0.75mg/0.03cc

Active Comparator group

Description:

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)

Treatment:

Drug: Bevacizumab

Bevacizumab (Avastin) 0.625mg/0.025cc

Active Comparator group

Description:

1/3 of patients will be randomized to this treatment in 1 eye (study eye) and the other eye will receive laser (fellow eye).

Treatment:

Drug: Bevacizumab

Laser ablation

Active Comparator group

Description:

1/3 of study participants will be randomized to this treatment in both eyes (study eye and fellow eye)

Treatment:

Drug: Bevacizumab