Clinical Trial: Phase 1 Trial of Bevacizumab Treatment for Severe Retinopathy of Prematurity

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Phase 1 Trial of Bevacizumab Treatment for Severe Retinopathy of Prematurity

Brief Summary: 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.

Detailed Summary: 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.
Sponsor: Jaeb Center for Health Research

Current Primary Outcome: 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.



Original Primary Outcome:

  • Successful Treatment of ROP at 0.25mg [ 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.

  • Successful Treatment of ROP at 0.125mg [ 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

    Current Secondary Outcome:

    • 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, and a 95% confidence interval calculated for the change.
    • 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, and a 95% confidence interval calculated for the change.
    • 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.
    • 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.
    • Number of study eye and fellow eyes requiring additional treatment/s for ROP, and if retreated, type of treatment [ Time Frame: 12-month corrected age ]
      12-month corrected age calculated as the estimated date of confinement (EDC), or due date, plus 12 months
    • 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
    • Assessment of vision [ Time Frame: 12-month corrected age ]
      12-month corrected age calculated as the estimated date of confinement (EDC), or due date, plus 12 months
    • 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

    • 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

    • Proportion 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
    • Proportion of infant deaths [ Time Frame: Enrollment to 12-month corrected age ]

    • 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 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.
    • 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, and a 95% confidence interval calculated for the change.
    • 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.
    • 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.
    • Time Since Initial Discharge [ Time Frame: 12-month corrected age ]
      12-month corrected age calculated as the estimated date of confinement (EDC), or due date, plus 12 months
    • Number of Times Re-hospitalized by 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
    • Number of infants with an increase in oxygen requirement prior to injection [ Time Frame: 12-month corrected age ]
      12-month corrected age calculated as the estimated date of confinement (EDC), or due date, plus 12 months
    • Number of infants with periventricular leukomalacia [ Time Frame: 12-month corrected age ]
      12-month corrected age calculated as the estimated date of confinement (EDC), or due date, plus 12 months
    • Number of study eye and fellow eyes requiring additional treatment/s for ROP, and if retreated, type of treatment [ Time Frame: 12-month corrected age ]
      12-month corrected age calculated as the estimated date of confinement (EDC), or due date, plus 12 months
    • 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
    • Assessment of vision [ Time Frame: 12-month corrected age ]
      12-month corrected age calculated as the estimated date of confinement (EDC), or due date, plus 12 months
    • Most recent head circumference [ Time Frame: 12-month corrected age ]

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

      Most recent head circumference (in centimeters), reported by z scores

    • Most recent weight [ Time Frame: 12-month corrected age ]
      12-month corrected age calculated as the estimated date of confinement (EDC), or due date, plus 12 months Most recent weight (in grams), reported by z scores
    • Proportion of infants for whom at least one event was reported [ Time Frame: Enrollment to completion ]

      Information By: Jaeb Center for Health Research

      Dates:
      Date Received: February 17, 2015
      Date Started: April 28, 2015
      Date Completion: March 2018
      Last Updated: April 12, 2017
      Last Verified: April 2017