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Completed

NCT Number: NCT02390531

Phase 1 Trial of Bevacizumab Treatment for Severe Retinopathy of Prematurity

The purpose of this study is to find a dose of intravitreal bevacizumab that is lower than currently used for severe retinopathy of prematurity (ROP), is effective in this study, and can be tested in future larger studies.

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Key information

Conditions

Retinopathy of Prematurity Congenital, Hereditary, and Neonatal Diseases and Abnormalities Eye Diseases Infant, Newborn, Diseases Infant, Premature, Diseases Retinal Diseases

Age range

Up to 6 month

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

The Emory Eye Center, Atlanta, Georgia, United States

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About this study

Despite promising initial results using empirical doses of bevacizumab based on half the adult dose for treatment of acute severe ROP, little is known about lower doses of bevacizumab for ROP. An increasing number of ophthalmologists are treating premature infants with severe ROP using bevacizumab. Given the potential systemic and ocular adverse effects of intravitreal bevacizumab injections, determining a lower effective dose of bevacizumab is an important next step. The proposed study will test progressively lower doses to find a dose to take forward to a future larger study.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Type 1 ROP; defined as:
  • Zone I, any stage ROP with plus disease, or
  • Zone I, stage 3 ROP without plus disease, or
  • Zone II, stage 2 or 3 ROP with plus disease
  • No previous treatment for ROP in the study eye; no previous bevacizumab treatment in the non-study eye

Exclusion criteria

The following exclusions apply to the study eye:

  • Nasolacrimal duct obstruction
  • Major ocular anomalies (e.g., cataract, coloboma)
  • Any opacity that precludes an adequate view of the retina

If purulent ocular discharge is present in either eye, then the infant is ineligible.

Treatment and study plan

Bevacizumab

Drug

Varying dosages in 10µl

Other names: Avastin

Primary outcomes

  1. Number of Participants With Successful Treatment of ROP

    Time frame: 4 weeks post-injection

    Success is defined as improvement* by the 4-day exam and no recurrence of type 1 ROP or severe neovascularization requiring additional treatment within 4 weeks of injection.

    • For infants with plus disease, improvement by the 4-day post-injection exam is defined as plus disease no longer being present. For infants with type 1 ROP without plus disease (i.e., zone I, stage 3), improvement by the 4-day post-injection exam is defined as: (1) a significant reduction in severity and/or extent of extraretinal neovascularization, and, (2) if pre-plus was present pre-injection, reduction in the degree of abnormal vascular dilation and/or tortuosity.

    A dose will be considered effective if it successfully treats at least 80% of subjects.

Secondary outcomes

  1. Distribution of VEGF Levels

    Time frame: 2 weeks post-injection

    The parents of each infant enrolled in the study will be given the option to participate in a study to measure levels of vascular endothelial growth factor (VEGF) and Avastin in the plasma. Participants in this optional study will have blood collected for analysis The distribution of VEGF and Avastin levels (median, range, and quartiles) will be described before injection, and at 2 weeks and 4 weeks post-injection. For each dosage level, at 2, and 4-weeks post-injection, the change from pre-injection will be calculated.

  2. Distribution of VEGF Levels

    Time frame: 4 weeks post-injection

    The parents of each infant enrolled in the study will be given the option to participate in a study to measure levels of VEGF and Avastin in the plasma. Participants in this optional study will have blood collected for analysis The distribution of VEGF and Avastin levels (median, range, and quartiles) will be described before injection, and at 2 weeks and 4 weeks post-injection. For each dosage level, at 2, and 4-weeks post-injection, the change from pre-injection will be calculated.

  3. Distribution of Avastin Levels

    Time frame: 2 weeks post-injection

    The parents of each infant enrolled in the study will be given the option to participate in a study to measure levels of VEGF and Avastin in the plasma. Participants in this optional study will have blood collected for analysis The distribution of VEGF and Avastin levels (median, range, and quartiles) will be described before injection, and at 2 weeks and 4 weeks post-injection. For each dosage level, at 2, and 4-weeks post-injection, the change from pre-injection will be calculated, and a 95% confidence interval calculated for the change.

  4. Distribution of Avastin Levels

    Time frame: 4 weeks post-injection

    The parents of each infant enrolled in the study will be given the option to participate in a study to measure levels of VEGF and Avastin in the plasma. Participants in this optional study will have blood collected for analysis The distribution of VEGF and Avastin levels (median, range, and quartiles) will be described before injection, and at 2 weeks and 4 weeks post-injection. For each dosage level, at 2, and 4-weeks post-injection, the change from pre-injection will be calculated, and a 95% confidence interval calculated for the change.

  5. Number of Study Eyes Requiring Additional Treatment/s for ROP

    Time frame: 12-month corrected age

    12-month corrected age calculated as the estimated date of confinement (EDC), or due date, plus 12 months

  6. Any Adverse Events or Complications Since the 4-week Exam

    Time frame: 12-month corrected age

    12-month corrected age calculated as the estimated date of confinement (EDC), or due date, plus 12 months

  7. Visual Fixation Status at 12 Months

    Time frame: 12-month corrected age

    12-month corrected age calculated as the estimated date of confinement (EDC), or due date, plus 12 months

  8. Proportion of Infants for Whom at Least One Event Was Reported

    Time frame: Enrollment to 12-month corrected age

    Adverse events reported at any time during the study will be tabulated for all enrolled infants and coded using the MedRA system. For each dosage level, an estimate and 95% confidence interval of the proportions will be obtained using the exact binomial method

    12-month corrected age calculated as the estimated date of confinement (EDC), or due date, plus 12 months

  9. Proportion of Infants With an Adverse Event Thought by Investigator to be Related to Study Drug

    Time frame: Enrollment to 12-month corrected age

    Adverse events reported at any time during the study will be tabulated for all enrolled infants and coded using the MedRA system. For each dosage level, an estimate and 95% confidence interval of the proportions will be obtained using the exact binomial method

    12-month corrected age calculated as the estimated date of confinement (EDC), or due date, plus 12 months

  10. Count of Infants for Whom at Least One Serious Adverse Event Was Reported

    Time frame: Enrollment to 12-month corrected age

    Adverse events reported at any time during the study will be tabulated for all enrolled infants and coded using the MedRA system. For each dosage level, an estimate and 95% confidence interval of the proportions will be obtained using the exact binomial method.

  11. Number of Infant Deaths

    Time frame: Enrollment to 12-month corrected age

    Adverse events reported at any time during the study will be tabulated for all enrolled infants and coded using the MedRA system.

    12-month corrected age calculated as the estimated date of confinement (EDC), or due date, plus 12 months

  12. Number of Infants With 24-Month Extended Follow Up Exam

    Time frame: 24-month corrected age

    A subset of infants enrolled in ROP1 will have extended follow up consisting of one additional office exam with developmental testing.

    This testing will provide a cross-sectional evaluation of visual acuity, refractive error, and development at the adjusted age 24-month visit.

    24-month corrected age calculated as the estimated date of confinement (EDC), or due date, plus 24 months.

  13. Number of Fellow Eyes Requiring Additional Treatment/s for ROP

    Time frame: 12-month corrected age

    12-month corrected age calculated as the estimated date of confinement (EDC), or due date, plus 12 months

Sponsors and collaborators

Lead sponsor

Jaeb Center for Health Research

Other

Collaborators

  • National Eye Institute (NEI)
  • Pediatric Eye Disease Investigator Group

Registry information

Acronym: ROP1

Important dates

Study start
2015
Primary completion
2019
Study completion
2021
First posted
Mar 17, 2015
Registry last updated
Nov 3, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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