NCT02390531

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
120

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Apr 2015

Longer than P75 for phase_1

Geographic Reach
1 country

11 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 17, 2015

Completed
28 days until next milestone

First Posted

Study publicly available on registry

March 17, 2015

Completed
1 month until next milestone

Study Start

First participant enrolled

April 28, 2015

Completed
4.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 4, 2019

Completed
1.9 years until next milestone

Study Completion

Last participant's last visit for all outcomes

May 11, 2021

Completed
1.5 years until next milestone

Results Posted

Study results publicly available

November 3, 2022

Completed
Last Updated

November 3, 2022

Status Verified

November 1, 2022

Enrollment Period

4.1 years

First QC Date

February 17, 2015

Results QC Date

April 28, 2022

Last Update Submit

November 1, 2022

Conditions

Retinopathy of Prematurity

Keywords

Retinopathy of PrematurityBevacizumabROP

Outcome Measures

Primary Outcomes (1)

  • Number of Participants With Successful Treatment of ROP

    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 Outcomes (13)

  • Distribution of VEGF Levels

    2 weeks post-injection

  • Distribution of VEGF Levels

    4 weeks post-injection

  • Distribution of Avastin Levels

    2 weeks post-injection

  • Distribution of Avastin Levels

    4 weeks post-injection

  • Number of Study Eyes Requiring Additional Treatment/s for ROP

    12-month corrected age

  • +8 more secondary outcomes

Study Arms (8)

Bevacizumab 0.250 mg

EXPERIMENTAL

Dosage of injected Bevacizumab to be studied

Drug: Bevacizumab

Bevacizumab 0.125 mg

EXPERIMENTAL

Dosage of injected Bevacizumab to be studied

Drug: Bevacizumab

Bevacizumab 0.063 mg

EXPERIMENTAL

Dosage of injected Bevacizumab to be studied

Drug: Bevacizumab

Bevacizumab 0.031 mg

EXPERIMENTAL

Dosage of injected Bevacizumab to be studied

Drug: Bevacizumab

Bevacizumab 0.016 mg

EXPERIMENTAL

Dosage of injected Bevacizumab to be studied

Drug: Bevacizumab

Bevacizumab 0.008 mg

EXPERIMENTAL

Dosage of injected Bevacizumab to be studied

Drug: Bevacizumab

Bevacizumab 0.004 mg

EXPERIMENTAL

Dosage of injected Bevacizumab to be studied

Drug: Bevacizumab

Bevacizumab 0.002 mg

EXPERIMENTAL

Dosage of injected Bevacizumab to be studied

Drug: Bevacizumab

Interventions

BevacizumabDRUG

Varying dosages in 10µl

Also known as: Avastin
Bevacizumab 0.002 mgBevacizumab 0.004 mgBevacizumab 0.008 mgBevacizumab 0.016 mgBevacizumab 0.031 mgBevacizumab 0.063 mgBevacizumab 0.125 mgBevacizumab 0.250 mg

Eligibility Criteria

AgeUp to 6 Months
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • 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

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (11)

The Emory Eye Center

Atlanta, Georgia, 30322, United States

Location

Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

Location

Wilmer Institute

Baltimore, Maryland, 21287, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Duke University Eye Center

Durham, North Carolina, 27710, United States

Location

Cincinnati Children's Hospital

Cincinnati, Ohio, 45229, United States

Location

Pediatric Ophthalmology Associates, Inc.

Columbus, Ohio, 43205, United States

Location

Dean A. McGee Eye Institute, University of Oklahoma

Oklahoma City, Oklahoma, 73104, United States

Location

Texas Children's Hospital - Dept. Of Ophthalmology

Houston, Texas, 77030, United States

Location

University of Utah Moran Eye Center

Salt Lake City, Utah, 84132, United States

Location

Virginia Pediatric Eye Center

Norfolk, Virginia, 23502, United States

Location

Related Publications (5)

  • Wallace DK, Kraker RT, Freedman SF, Crouch ER, Hutchinson AK, Bhatt AR, Rogers DL, Yang MB, Haider KM, VanderVeen DK, Siatkowski RM, Dean TW, Beck RW, Repka MX, Smith LE, Good WV, Hartnett ME, Kong L, Holmes JM; Pediatric Eye Disease Investigator Group (PEDIG). Assessment of Lower Doses of Intravitreous Bevacizumab for Retinopathy of Prematurity: A Phase 1 Dosing Study. JAMA Ophthalmol. 2017 Jun 1;135(6):654-656. doi: 10.1001/jamaophthalmol.2017.1055.

    PMID: 28448664BACKGROUND

  • Kraker RT, Wallace DK, Beck RW, Saunders CT, Lorenzi E, Melia BM, Li Z; Pediatric Eye Disease Investigator Group. Choice of Dose Level for a Randomized Clinical Trial of Low-Dose Bevacizumab vs Laser for Type 1 Retinopathy of Prematurity. JAMA Ophthalmol. 2021 Oct 1;139(10):1143-1144. doi: 10.1001/jamaophthalmol.2021.3192.

    PMID: 34410311BACKGROUND

  • Wallace DK, Dean TW, Hartnett ME, Kong L, Smith LE, Hubbard GB, McGregor ML, Jordan CO, Mantagos IS, Bell EF, Kraker RT; Pediatric Eye Disease Investigator Group. A Dosing Study of Bevacizumab for Retinopathy of Prematurity: Late Recurrences and Additional Treatments. Ophthalmology. 2018 Dec;125(12):1961-1966. doi: 10.1016/j.ophtha.2018.05.001. Epub 2018 Jun 7.

    PMID: 29887334RESULT

  • Crouch ER, Kraker RT, Wallace DK, Holmes JM, Repka MX, Collinge JE, Bremer DL, Gray ME, Smith HA, Steinkuller PG; Writing Committee for Pediatric Eye Disease Investigator Group. Secondary 12-Month Ocular Outcomes of a Phase 1 Dosing Study of Bevacizumab for Retinopathy of Prematurity. JAMA Ophthalmol. 2020 Jan 1;138(1):14-20. doi: 10.1001/jamaophthalmol.2019.4488.

    PMID: 31697304RESULT

  • Wallace DK, Kraker RT, Freedman SF, Crouch ER, Bhatt AR, Hartnett ME, Yang MB, Rogers DL, Hutchinson AK, VanderVeen DK, Haider KM, Siatkowski RM, Dean TW, Beck RW, Repka MX, Smith LE, Good WV, Kong L, Cotter SA, Holmes JM; Pediatric Eye Disease Investigator Group (PEDIG). Short-term Outcomes After Very Low-Dose Intravitreous Bevacizumab for Retinopathy of Prematurity. JAMA Ophthalmol. 2020 Jun 1;138(6):698-701. doi: 10.1001/jamaophthalmol.2020.0334.

    PMID: 32324197RESULT

Related Links

MeSH Terms

Conditions

Retinopathy of Prematurity

Interventions

Bevacizumab

Condition Hierarchy (Ancestors)

Retinal DiseasesEye DiseasesInfant, Premature, DiseasesInfant, Newborn, DiseasesCongenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Results Point of Contact

Title
Raymond Kraker, PEDIG Coordinating Center Director
Organization
Jaeb Center for Health Research
rkraker@jaeb.org
8139758690

Study Officials

  • David K Wallace, MD, MPH

    Indiana University

    STUDY CHAIR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Model Details: 8 bevacizumab doses were evaluated in this dose de-escalation study in the following dosage amounts: 0.250mg, 0.125mg, 0.063mg, 0.031mg, 0.016mg, 0.008mg, 0.004mg, 0.002mg. Each dose was planned to be used in up to 14 infants to ensure at least 10 infants with 4-week outcomes
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 17, 2015

First Posted

March 17, 2015

Study Start

April 28, 2015

Primary Completion

June 4, 2019

Study Completion

May 11, 2021

Last Updated

November 3, 2022

Results First Posted

November 3, 2022

Record last verified: 2022-11

Data Sharing

IPD Sharing
Will share

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.

Locations

US(11)