Phase 1 Trial of Bevacizumab Treatment for Severe Retinopathy of Prematurity

Retinopathy of Prematurity Clinical Trial

— ROP1  

Official title:

Phase 1 Trial of Bevacizumab Treatment for Severe Retinopathy of Prematurity

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02390531
• Other study ID #: ROP1
• Secondary ID: 2U10EY011751
• Status: Completed
• Phase: Phase 1
• Start date: April 28, 2015
• Est. completion date: May 11, 2021

Study information

• Verified date: November 2022
• Source: Jaeb Center for Health Research
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 120
• Est. completion date: May 11, 2021
• Est. primary completion date: June 4, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 6 Months

Eligibility

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.

Related Conditions & MeSH terms

• Premature Birth
• Retinal Diseases
• Retinopathy of Prematurity

Intervention

Drug:
• Bevacizumab
Varying dosages in 10µl

Locations

Country	Name	City	State
United States	The Emory Eye Center	Atlanta	Georgia
United States	Wilmer Institute	Baltimore	Maryland
United States	Boston Children's Hospital	Boston	Massachusetts
United States	Cincinnati Children's Hospital	Cincinnati	Ohio
United States	Pediatric Ophthalmology Associates, Inc.	Columbus	Ohio
United States	Duke University Eye Center	Durham	North Carolina
United States	Texas Children's Hospital - Dept. Of Ophthalmology	Houston	Texas
United States	Riley Hospital for Children	Indianapolis	Indiana
United States	Virginia Pediatric Eye Center	Norfolk	Virginia
United States	Dean A. McGee Eye Institute, University of Oklahoma	Oklahoma City	Oklahoma
United States	University of Utah Moran Eye Center	Salt Lake City	Utah

Sponsors (3)

Lead Sponsor	Collaborator
Jaeb Center for Health Research	National Eye Institute (NEI), Pediatric Eye Disease Investigator Group

Country where clinical trial is conducted

United States, 

References & Publications (5)

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 f — View Citation

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. — View Citation

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 Additiona — View Citation

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 Investigat — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Distribution of VEGF Levels	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
Secondary	Distribution of VEGF Levels	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
Secondary	Distribution of Avastin Levels	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
Secondary	Distribution of Avastin Levels	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
Secondary	Number of Study Eyes Requiring Additional Treatment/s for ROP	12-month corrected age calculated as the estimated date of confinement (EDC), or due date, plus 12 months	12-month corrected age
Secondary	Any Adverse Events or Complications Since the 4-week Exam	12-month corrected age calculated as the estimated date of confinement (EDC), or due date, plus 12 months	12-month corrected age
Secondary	Visual Fixation Status at 12 Months	12-month corrected age calculated as the estimated date of confinement (EDC), or due date, plus 12 months	12-month corrected age
Secondary	Proportion of Infants for Whom at Least One Event Was Reported	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
Secondary	Proportion of Infants With an Adverse Event Thought by Investigator to be Related to Study Drug	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
Secondary	Count of Infants for Whom at Least One Serious Adverse Event Was Reported	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
Secondary	Number of Infant Deaths	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
Secondary	Number of Infants With 24-Month Extended Follow Up Exam	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
Secondary	Number of Fellow Eyes Requiring Additional Treatment/s for ROP	12-month corrected age calculated as the estimated date of confinement (EDC), or due date, plus 12 months	12-month corrected age

External Links

•   PEDIG Public Website