Use of Pan-Vascular Endothelial Growth Factor Receptor (Pan-VEGF) Blockade for the Treatment of Retinopathy of Prematurity (ROP) (Compassionate Use BLOCK-ROP)

Expanded access is temporarily not available for this treatment.
Sponsor:
Information provided by:
Children's Hospital Los Angeles
ClinicalTrials.gov Identifier:
NCT00870636
First received: March 26, 2009
Last updated: March 27, 2009
Last verified: March 2009
  Purpose

The purpose of this study is to provide access to intravitreal injection of Avastin in high-risk infants who do not otherwise qualify for study NCT00702819, an investigational multi-site study examining Avastin use for retinopathy of prematurity.


Condition Intervention
Retinopathy of Prematurity
Drug: Bevacizumab (Avastin)

Study Type: Expanded Access     What is Expanded Access?
Official Title: Compassionate Use Pan-VEGF Blockade for the Treatment of ROP (Compassionate Use BLOCK-ROP) Trial

Resource links provided by NLM:


Further study details as provided by Children's Hospital Los Angeles:

Intervention Details:
    Drug: Bevacizumab (Avastin)
    Dosage of 0.75mg/0.03ml intravitreal injectable, one time only.
    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 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.

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, 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.

There is a nearly identical multi-site trial (NCT00702819) currently recruiting, which Childrens Hospital Los Angeles is a part of. However, that study has limiting enrollment criteria; this compassionate-use study was created to provide access to bevacizumab (Avastin) for high-risk infants who do not qualify for study NCT00702819.

  Eligibility

Ages Eligible for Study:   30 Weeks and older
Genders Eligible for Study:   Both
Criteria

Inclusion Criteria:

  • Inborn babies at CHLA NICU
  • Outborn babies transferred to CHLA NICU
  • Zone 1 or 2 ROP
  • Adequate/appropriate laser ablation
  • Failed standard laser treatment (persistent Plus disease at a minimum of 1 week post-laser)
  • Post-menstrual age greater than 30 weeks

Exclusion Criteria:

  • Zone 3 ROP
  • Inadequate initial laser treatment
  • Most recent laser treatment less than 1 week
  • Evidence of tractional retinal detachment (exudative retinal detachment may be included in study group)
  • Post-menstrual age less than 30 weeks
  • Health not allowing for full protocol participation (determined by neonatologist)
  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: NCT00870636

Locations
United States, California
Childrens Hospital Los Angeles
Los Angeles, California, United States, 90027
Sponsors and Collaborators
Children's Hospital Los Angeles
Investigators
Principal Investigator: Thomas Lee, M.D. Children's Hospital Los Angeles
  More Information

No publications provided

Responsible Party: Thomas Lee, M.D., Childrens Hospital Los Angeles
ClinicalTrials.gov Identifier: NCT00870636     History of Changes
Other Study ID Numbers: 09-00044
Study First Received: March 26, 2009
Last Updated: March 27, 2009
Health Authority: United States: Food and Drug Administration

Keywords provided by Children's Hospital Los Angeles:
Pan-Vascular Endothelial Growth Factor Blockade
Safety
ROP
Bevacizumab
Avastin

Additional relevant MeSH terms:
Retinal Diseases
Retinopathy of Prematurity
Eye Diseases
Infant, Premature, Diseases
Infant, Newborn, Diseases
Mitogens
Endothelial Growth Factors
Bevacizumab
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Growth Substances
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 18, 2014