Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Phase 1 Trial of Bevacizumab Treatment for Severe Retinopathy of Prematurity (ROP1)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02390531
Recruitment Status : Active, not recruiting
First Posted : March 17, 2015
Last Update Posted : September 1, 2020
Sponsor:
Collaborators:
Pediatric Eye Disease Investigator Group
National Eye Institute (NEI)
Information provided by (Responsible Party):
Jaeb Center for Health Research

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.

Condition or disease Intervention/treatment Phase
Retinopathy of Prematurity Drug: Bevacizumab Phase 1

Detailed Description:
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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 121 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Phase 1 Trial of Bevacizumab Treatment for Severe Retinopathy of Prematurity
Actual Study Start Date : April 28, 2015
Actual Primary Completion Date : June 4, 2019
Estimated Study Completion Date : September 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Bevacizumab

Arm Intervention/treatment
Experimental: Bevacizumab
Dosage if injected Bevacizumab to be studied
Drug: Bevacizumab
Varying dosages in 10µl
Other Name: Avastin




Primary Outcome Measures :
  1. 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 Outcome Measures :
  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, and a 95% confidence interval calculated for the change.

  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, and a 95% confidence interval calculated for the change.

  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 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

  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. 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

  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. 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

  11. Proportion 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. 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


  12. 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.




Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   up to 6 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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
  2. 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:

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

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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02390531


Locations
Layout table for location information
United States, Georgia
The Emory Eye Center
Atlanta, Georgia, United States, 30322
United States, Indiana
Riley Hospital for Children
Indianapolis, Indiana, United States, 46202
United States, Maryland
Wilmer Institute
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Boston Children's Hospital
Boston, Massachusetts, United States, 02115
United States, North Carolina
Duke University Eye Center
Durham, North Carolina, United States, 27710
United States, Ohio
Cincinnati Children's Hospital
Cincinnati, Ohio, United States, 45229
Pediatric Ophthalmology Associates, Inc.
Columbus, Ohio, United States, 43205
United States, Oklahoma
Dean A. McGee Eye Institute, University of Oklahoma
Oklahoma City, Oklahoma, United States, 73104
United States, Texas
Texas Children's Hospital - Dept. Of Ophthalmology
Houston, Texas, United States, 77030
United States, Utah
University of Utah Moran Eye Center
Salt Lake City, Utah, United States, 84132
United States, Virginia
Virginia Pediatric Eye Center
Norfolk, Virginia, United States, 23502
Sponsors and Collaborators
Jaeb Center for Health Research
Pediatric Eye Disease Investigator Group
National Eye Institute (NEI)
Investigators
Layout table for investigator information
Study Chair: David K Wallace, MD, MPH Duke Eye Center
  Study Documents (Full-Text)

Documents provided by Jaeb Center for Health Research:
Informed Consent Form  [PDF] April 13, 2018

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Jaeb Center for Health Research
ClinicalTrials.gov Identifier: NCT02390531    
Other Study ID Numbers: ROP1
2U10EY011751 ( U.S. NIH Grant/Contract )
First Posted: March 17, 2015    Key Record Dates
Last Update Posted: September 1, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: In accordance with the NIH data sharing policy, a de-identified database is placed in the public domain on the PEDIG public website after the completion of each protocol and publication of the primary manuscript.
Time Frame: Data will be made available after publication of each primary manuscript.
Access Criteria: Users accessing the data must enter an email address.
Keywords provided by Jaeb Center for Health Research:
Retinopathy of Prematurity
Bevacizumab
ROP
Additional relevant MeSH terms:
Layout table for MeSH terms
Retinal Diseases
Retinopathy of Prematurity
Premature Birth
Eye Diseases
Obstetric Labor, Premature
Obstetric Labor Complications
Pregnancy Complications
Infant, Premature, Diseases
Infant, Newborn, Diseases
Bevacizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors