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

November 1, 2022 updated by: Jaeb Center for Health Research
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

120

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • The Emory Eye Center
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Riley Hospital for Children
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Wilmer Institute
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Boston Children's Hospital
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University Eye Center
    • Ohio
      • Cincinnati, Ohio, United States, 45229
        • Cincinnati Children's Hospital
      • Columbus, Ohio, United States, 43205
        • Pediatric Ophthalmology Associates, Inc.
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Dean A. McGee Eye Institute, University of Oklahoma
    • Texas
      • Houston, Texas, United States, 77030
        • Texas Children's Hospital - Dept. Of Ophthalmology
    • Utah
      • Salt Lake City, Utah, United States, 84132
        • University of Utah Moran Eye Center
    • Virginia
      • Norfolk, Virginia, United States, 23502
        • Virginia Pediatric Eye Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 6 months (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Bevacizumab 0.250 mg
Dosage of injected Bevacizumab to be studied
Drug: Bevacizumab
Varying dosages in 10µl
Other Names:
  • Avastin
Experimental: Bevacizumab 0.125 mg
Dosage of injected Bevacizumab to be studied
Drug: Bevacizumab
Varying dosages in 10µl
Other Names:
  • Avastin
Experimental: Bevacizumab 0.063 mg
Dosage of injected Bevacizumab to be studied
Drug: Bevacizumab
Varying dosages in 10µl
Other Names:
  • Avastin
Experimental: Bevacizumab 0.031 mg
Dosage of injected Bevacizumab to be studied
Drug: Bevacizumab
Varying dosages in 10µl
Other Names:
  • Avastin
Experimental: Bevacizumab 0.016 mg
Dosage of injected Bevacizumab to be studied
Drug: Bevacizumab
Varying dosages in 10µl
Other Names:
  • Avastin
Experimental: Bevacizumab 0.008 mg
Dosage of injected Bevacizumab to be studied
Drug: Bevacizumab
Varying dosages in 10µl
Other Names:
  • Avastin
Experimental: Bevacizumab 0.004 mg
Dosage of injected Bevacizumab to be studied
Drug: Bevacizumab
Varying dosages in 10µl
Other Names:
  • Avastin
Experimental: Bevacizumab 0.002 mg
Dosage of injected Bevacizumab to be studied
Drug: Bevacizumab
Varying dosages in 10µl
Other Names:
  • Avastin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
4 weeks post-injection

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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 weeks post-injection
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.
4 weeks post-injection
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.
2 weeks post-injection
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.
4 weeks post-injection
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
12-month corrected age
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
12-month corrected age
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
12-month corrected age
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
Enrollment to 12-month corrected age
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
Enrollment to 12-month corrected age
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.
Enrollment to 12-month corrected age
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
Enrollment to 12-month corrected age
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.
24-month corrected age
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
12-month corrected age

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Jaeb Center for Health Research

Collaborators

National Eye Institute (NEI)
Pediatric Eye Disease Investigator Group

Investigators

  • Study Chair: David K Wallace, MD, MPH, Indiana University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 28, 2015

Primary Completion (Actual)

June 4, 2019

Study Completion (Actual)

May 11, 2021

Study Registration Dates

First Submitted

February 17, 2015

First Submitted That Met QC Criteria

March 10, 2015

First Posted (Estimate)

March 17, 2015

Study Record Updates

Last Update Posted (Actual)

November 3, 2022

Last Update Submitted That Met QC Criteria

November 1, 2022

Last Verified

November 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ROP1
  • 2U10EY011751 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD 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.

IPD Sharing Time Frame

Data will be made available after publication of each primary manuscript.

IPD Sharing Access Criteria

Users accessing the data must enter an email address.

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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