Retinopathy of Prematurity
Conditions
Keywords
Retinopathy of Prematurity, Bevacizumab, ROP
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 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.
Interventions
DRUGBevacizumab
Varying dosages in 10µl
Sponsors
Pediatric Eye Disease Investigator Group
National Eye Institute (NEI)
Jaeb Center for Health Research
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
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
Eligibility
Sex/Gender
ALL
Age
No minimum to 6 Months
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Successful Treatment of ROP | 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
| Measure | Time frame | Description |
|---|---|---|
| Distribution of Avastin Levels | 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. |
| Number of Study Eyes Requiring Additional Treatment/s for ROP | 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 | 12-month corrected age | 12-month corrected age calculated as the estimated date of confinement (EDC), or due date, plus 12 months |
| Visual Fixation Status at 12 Months | 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 | 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 |
| Distribution of VEGF Levels | 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. |
| Count of Infants for Whom at Least One Serious Adverse Event Was Reported | 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. |
| Number of Infant Deaths | 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 |
| Number of Infants With 24-Month Extended Follow Up Exam | 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. |
| Number of Fellow Eyes Requiring Additional Treatment/s for ROP | 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 With an Adverse Event Thought by Investigator to be Related to Study Drug | 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 |
Countries
United States
Participant flow
Recruitment details
Original reported enrollment was 121, however upon further review 2 patient identifiers were found to be the same patient, incorrectly enrolled twice, bringing the correct count to 120.
Participants by arm
| Arm | Count |
|---|---|
| Bevacizumab (0.25 mg) Dosage of injected Bevacizumab to be studied | 11 |
| Bevacizumab (0.125 mg) Dosage of injected Bevacizumab to be studied | 16 |
| Bevacizumab (0.0625 mg) Dosage of injected Bevacizumab to be studied | 24 |
| Bevacizumab (0.031 mg) Dosage of injected Bevacizumab to be studied | 10 |
| Bevacizumab (0.016 mg) Dosage of injected Bevacizumab to be studied | 14 |
| Bevacizumab (0.008 mg) Dosage of injected Bevacizumab to be studied | 9 |
| Bevacizumab (0.004 mg) Dosage of injected Bevacizumab to be studied | 12 |
| Bevacizumab (0.002 mg) Dosage of injected Bevacizumab to be studied | 24 |
| Total | 120 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 0 | 2 | 0 | 1 | 0 | 0 | 0 | 1 |
| Overall Study | Protocol Violation | 0 | 0 | 0 | 0 | 1 | 0 | 2 | 0 |
Baseline characteristics
| Characteristic | Bevacizumab (0.25 mg) | Bevacizumab (0.125 mg) | Bevacizumab (0.0625 mg) | Bevacizumab (0.031 mg) | Bevacizumab (0.016 mg) | Bevacizumab (0.008 mg) | Bevacizumab (0.004 mg) | Bevacizumab (0.002 mg) | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous Gestational age at enrollment | 24.81 Weeks STANDARD_DEVIATION 1.49 | 25.21 Weeks STANDARD_DEVIATION 2.22 | 24.82 Weeks STANDARD_DEVIATION 1.42 | 24.73 Weeks STANDARD_DEVIATION 1.12 | 24.48 Weeks STANDARD_DEVIATION 1.14 | 24.63 Weeks STANDARD_DEVIATION 1.48 | 24.45 Weeks STANDARD_DEVIATION 1.23 | 25.14 Weeks STANDARD_DEVIATION 2.02 | 24.84 Weeks STANDARD_DEVIATION 1.61 |
| Birth Weight | 726.27 grams STANDARD_DEVIATION 219.23 | 801.31 grams STANDARD_DEVIATION 514.35 | 652.08 grams STANDARD_DEVIATION 156.88 | 680.60 grams STANDARD_DEVIATION 167.17 | 677.93 grams STANDARD_DEVIATION 147.02 | 539.44 grams STANDARD_DEVIATION 133.19 | 624.67 grams STANDARD_DEVIATION 155.14 | 722.00 grams STANDARD_DEVIATION 357.65 | 686.97 grams STANDARD_DEVIATION 281.43 |
| Race/Ethnicity, Customized American Indian/Alaskan Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 5 Participants |
| Race/Ethnicity, Customized Black/African American | 2 Participants | 2 Participants | 3 Participants | 4 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 19 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 2 Participants | 3 Participants | 3 Participants | 2 Participants | 2 Participants | 1 Participants | 2 Participants | 2 Participants | 17 Participants |
| Race/Ethnicity, Customized More than 1 race | 0 Participants | 1 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 4 Participants |
| Race/Ethnicity, Customized Native Hawaiian/Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Unknown/Not Reported | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 3 Participants | 7 Participants |
| Race/Ethnicity, Customized White | 7 Participants | 10 Participants | 12 Participants | 2 Participants | 9 Participants | 3 Participants | 7 Participants | 15 Participants | 65 Participants |
| Sex: Female, Male Female | 6 Participants | 4 Participants | 12 Participants | 4 Participants | 3 Participants | 7 Participants | 3 Participants | 10 Participants | 49 Participants |
| Sex: Female, Male Male | 5 Participants | 12 Participants | 12 Participants | 6 Participants | 11 Participants | 2 Participants | 9 Participants | 14 Participants | 71 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 3 / 16 | 2 / 24 | 2 / 10 | 1 / 14 | 0 / 9 | 0 / 12 | 1 / 24 |
| other Total, other adverse events | 4 / 11 | 3 / 16 | 4 / 24 | 1 / 10 | 4 / 14 | 1 / 9 | 5 / 12 | 9 / 24 |
| serious Total, serious adverse events | 1 / 11 | 3 / 16 | 3 / 24 | 1 / 10 | 1 / 14 | 1 / 9 | 5 / 12 | 4 / 24 |
Outcome results
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.
Time frame: 4 weeks post-injection
Population: Seven infants were excluded (4 infants died prior to 4-week outcome examination; 1 failed, but it was not confirmed by second examiner; 1 was injected with the wrong dose in the study eye; and 1 had the fellow eye treated in the absence of type 1 ROP within one week of the study eye).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Bevacizumab | Number of Participants With Successful Treatment of ROP | 0.250 mg Bevacizumab | 11 Participants |
| Bevacizumab | Number of Participants With Successful Treatment of ROP | 0.125 mg Bevacizumab | 14 Participants |
| Bevacizumab | Number of Participants With Successful Treatment of ROP | 0.063 mg Bevacizumab | 21 Participants |
| Bevacizumab | Number of Participants With Successful Treatment of ROP | 0.031 mg Bevacizumab | 9 Participants |
| Bevacizumab | Number of Participants With Successful Treatment of ROP | 0.016 mg Bevacizumab | 13 Participants |
| Bevacizumab | Number of Participants With Successful Treatment of ROP | 0.008 mg Bevacizumab | 9 Participants |
| Bevacizumab | Number of Participants With Successful Treatment of ROP | 0.004 mg Bevacizumab | 9 Participants |
| Bevacizumab | Number of Participants With Successful Treatment of ROP | 0.002 mg Bevacizumab | 17 Participants |
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
Time frame: 12-month corrected age
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Bevacizumab | Any Adverse Events or Complications Since the 4-week Exam | 4 Participants |
| Bevacizumab (0.0125 mg) | Any Adverse Events or Complications Since the 4-week Exam | 3 Participants |
| Bevacizumab (0.0625 mg) | Any Adverse Events or Complications Since the 4-week Exam | 4 Participants |
| Bevacizumab (0.031 mg) | Any Adverse Events or Complications Since the 4-week Exam | 1 Participants |
| Bevacizumab (0.016 mg) | Any Adverse Events or Complications Since the 4-week Exam | 4 Participants |
| Bevacizumab (0.008 mg) | Any Adverse Events or Complications Since the 4-week Exam | 1 Participants |
| Bevacizumab (0.004 mg) | Any Adverse Events or Complications Since the 4-week Exam | 5 Participants |
| Bevacizumab (0.002 mg) | Any Adverse Events or Complications Since the 4-week Exam | 9 Participants |
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.
Time frame: Enrollment to 12-month corrected age
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Bevacizumab | Count of Infants for Whom at Least One Serious Adverse Event Was Reported | 4 Participants |
| Bevacizumab (0.0125 mg) | Count of Infants for Whom at Least One Serious Adverse Event Was Reported | 2 Participants |
| Bevacizumab (0.0625 mg) | Count of Infants for Whom at Least One Serious Adverse Event Was Reported | 3 Participants |
| Bevacizumab (0.031 mg) | Count of Infants for Whom at Least One Serious Adverse Event Was Reported | 1 Participants |
| Bevacizumab (0.016 mg) | Count of Infants for Whom at Least One Serious Adverse Event Was Reported | 1 Participants |
| Bevacizumab (0.008 mg) | Count of Infants for Whom at Least One Serious Adverse Event Was Reported | 0 Participants |
| Bevacizumab (0.004 mg) | Count of Infants for Whom at Least One Serious Adverse Event Was Reported | 5 Participants |
| Bevacizumab (0.002 mg) | Count of Infants for Whom at Least One Serious Adverse Event Was Reported | 4 Participants |
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.
Time frame: 2 weeks post-injection
Population: Given the optional nature of this blood draw, outcomes were only collected for 56 infants. Given small sample size, we combined all dose levels and reported for those who were enrolled in this optional portion of the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab | Distribution of Avastin Levels | 364 ng/mL |
| Bevacizumab (0.0125 mg) | Distribution of Avastin Levels | 231 ng/mL |
| Bevacizumab (0.0625 mg) | Distribution of Avastin Levels | 292 ng/mL |
| Bevacizumab (0.031 mg) | Distribution of Avastin Levels | 167 ng/mL |
| Bevacizumab (0.016 mg) | Distribution of Avastin Levels | 79 ng/mL |
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.
Time frame: 4 weeks post-injection
Population: Given the optional nature of the blood draw and loss to follow up, 4 week data was only collected for 49 infants. Given small sample size, we combined all dose levels and reported for those who were enrolled in this optional portion of the study. Reporting the results overall matches the published MS.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bevacizumab | Distribution of Avastin Levels | 281 ng/mL |
| Bevacizumab (0.0125 mg) | Distribution of Avastin Levels | 196 ng/mL |
| Bevacizumab (0.0625 mg) | Distribution of Avastin Levels | 254 ng/mL |
| Bevacizumab (0.031 mg) | Distribution of Avastin Levels | 115 ng/mL |
| Bevacizumab (0.016 mg) | Distribution of Avastin Levels | 67 ng/mL |
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.
Time frame: 4 weeks post-injection
Population: In this optional portion of the study, data is available for 61 infants.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Bevacizumab | Distribution of VEGF Levels | Decrease in VEGF by 1% to <25% | 2 Participants |
| Bevacizumab | Distribution of VEGF Levels | Any increase in VEGF | 1 Participants |
| Bevacizumab | Distribution of VEGF Levels | Decrease in VEGF by greater than or equal to 50% | 3 Participants |
| Bevacizumab | Distribution of VEGF Levels | Decrease in VEGF by 25% to <50% | 3 Participants |
| Bevacizumab (0.0125 mg) | Distribution of VEGF Levels | Decrease in VEGF by greater than or equal to 50% | 7 Participants |
| Bevacizumab (0.0125 mg) | Distribution of VEGF Levels | Decrease in VEGF by 1% to <25% | 1 Participants |
| Bevacizumab (0.0125 mg) | Distribution of VEGF Levels | Any increase in VEGF | 0 Participants |
| Bevacizumab (0.0125 mg) | Distribution of VEGF Levels | Decrease in VEGF by 25% to <50% | 2 Participants |
| Bevacizumab (0.0625 mg) | Distribution of VEGF Levels | Decrease in VEGF by 25% to <50% | 3 Participants |
| Bevacizumab (0.0625 mg) | Distribution of VEGF Levels | Any increase in VEGF | 2 Participants |
| Bevacizumab (0.0625 mg) | Distribution of VEGF Levels | Decrease in VEGF by 1% to <25% | 1 Participants |
| Bevacizumab (0.0625 mg) | Distribution of VEGF Levels | Decrease in VEGF by greater than or equal to 50% | 7 Participants |
| Bevacizumab (0.031 mg) | Distribution of VEGF Levels | Any increase in VEGF | 1 Participants |
| Bevacizumab (0.031 mg) | Distribution of VEGF Levels | Decrease in VEGF by 1% to <25% | 0 Participants |
| Bevacizumab (0.031 mg) | Distribution of VEGF Levels | Decrease in VEGF by greater than or equal to 50% | 4 Participants |
| Bevacizumab (0.031 mg) | Distribution of VEGF Levels | Decrease in VEGF by 25% to <50% | 1 Participants |
| Bevacizumab (0.016 mg) | Distribution of VEGF Levels | Decrease in VEGF by 1% to <25% | 1 Participants |
| Bevacizumab (0.016 mg) | Distribution of VEGF Levels | Decrease in VEGF by 25% to <50% | 1 Participants |
| Bevacizumab (0.016 mg) | Distribution of VEGF Levels | Any increase in VEGF | 2 Participants |
| Bevacizumab (0.016 mg) | Distribution of VEGF Levels | Decrease in VEGF by greater than or equal to 50% | 4 Participants |
| Bevacizumab (0.008 mg) | Distribution of VEGF Levels | Decrease in VEGF by greater than or equal to 50% | 4 Participants |
| Bevacizumab (0.008 mg) | Distribution of VEGF Levels | Decrease in VEGF by 1% to <25% | 0 Participants |
| Bevacizumab (0.008 mg) | Distribution of VEGF Levels | Decrease in VEGF by 25% to <50% | 1 Participants |
| Bevacizumab (0.008 mg) | Distribution of VEGF Levels | Any increase in VEGF | 1 Participants |
| Bevacizumab (0.004 mg) | Distribution of VEGF Levels | Decrease in VEGF by greater than or equal to 50% | 0 Participants |
| Bevacizumab (0.004 mg) | Distribution of VEGF Levels | Decrease in VEGF by 25% to <50% | 0 Participants |
| Bevacizumab (0.004 mg) | Distribution of VEGF Levels | Decrease in VEGF by 1% to <25% | 0 Participants |
| Bevacizumab (0.004 mg) | Distribution of VEGF Levels | Any increase in VEGF | 4 Participants |
| Bevacizumab (0.002 mg) | Distribution of VEGF Levels | Decrease in VEGF by greater than or equal to 50% | 2 Participants |
| Bevacizumab (0.002 mg) | Distribution of VEGF Levels | Any increase in VEGF | 3 Participants |
| Bevacizumab (0.002 mg) | Distribution of VEGF Levels | Decrease in VEGF by 25% to <50% | 0 Participants |
| Bevacizumab (0.002 mg) | Distribution of VEGF Levels | Decrease in VEGF by 1% to <25% | 0 Participants |
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.
Time frame: 2 weeks post-injection
Population: In this optional portion of the study, data is available for 66 infants.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Bevacizumab | Distribution of VEGF Levels | Any increase in VEGF | 0 Participants |
| Bevacizumab | Distribution of VEGF Levels | Decrease in VEGF by 1% to <25% | 2 Participants |
| Bevacizumab | Distribution of VEGF Levels | Decrease in VEGF by 25% to <50% | 4 Participants |
| Bevacizumab | Distribution of VEGF Levels | Decrease in VEGF by greater than or equal to 50% | 3 Participants |
| Bevacizumab (0.0125 mg) | Distribution of VEGF Levels | Decrease in VEGF by 25% to <50% | 2 Participants |
| Bevacizumab (0.0125 mg) | Distribution of VEGF Levels | Decrease in VEGF by 1% to <25% | 0 Participants |
| Bevacizumab (0.0125 mg) | Distribution of VEGF Levels | Any increase in VEGF | 0 Participants |
| Bevacizumab (0.0125 mg) | Distribution of VEGF Levels | Decrease in VEGF by greater than or equal to 50% | 8 Participants |
| Bevacizumab (0.0625 mg) | Distribution of VEGF Levels | Any increase in VEGF | 4 Participants |
| Bevacizumab (0.0625 mg) | Distribution of VEGF Levels | Decrease in VEGF by greater than or equal to 50% | 9 Participants |
| Bevacizumab (0.0625 mg) | Distribution of VEGF Levels | Decrease in VEGF by 1% to <25% | 1 Participants |
| Bevacizumab (0.0625 mg) | Distribution of VEGF Levels | Decrease in VEGF by 25% to <50% | 2 Participants |
| Bevacizumab (0.031 mg) | Distribution of VEGF Levels | Any increase in VEGF | 0 Participants |
| Bevacizumab (0.031 mg) | Distribution of VEGF Levels | Decrease in VEGF by 1% to <25% | 1 Participants |
| Bevacizumab (0.031 mg) | Distribution of VEGF Levels | Decrease in VEGF by 25% to <50% | 1 Participants |
| Bevacizumab (0.031 mg) | Distribution of VEGF Levels | Decrease in VEGF by greater than or equal to 50% | 6 Participants |
| Bevacizumab (0.016 mg) | Distribution of VEGF Levels | Decrease in VEGF by 25% to <50% | 1 Participants |
| Bevacizumab (0.016 mg) | Distribution of VEGF Levels | Any increase in VEGF | 2 Participants |
| Bevacizumab (0.016 mg) | Distribution of VEGF Levels | Decrease in VEGF by 1% to <25% | 0 Participants |
| Bevacizumab (0.016 mg) | Distribution of VEGF Levels | Decrease in VEGF by greater than or equal to 50% | 6 Participants |
| Bevacizumab (0.008 mg) | Distribution of VEGF Levels | Decrease in VEGF by greater than or equal to 50% | 5 Participants |
| Bevacizumab (0.008 mg) | Distribution of VEGF Levels | Any increase in VEGF | 0 Participants |
| Bevacizumab (0.008 mg) | Distribution of VEGF Levels | Decrease in VEGF by 25% to <50% | 0 Participants |
| Bevacizumab (0.008 mg) | Distribution of VEGF Levels | Decrease in VEGF by 1% to <25% | 0 Participants |
| Bevacizumab (0.004 mg) | Distribution of VEGF Levels | Decrease in VEGF by greater than or equal to 50% | 0 Participants |
| Bevacizumab (0.004 mg) | Distribution of VEGF Levels | Decrease in VEGF by 25% to <50% | 0 Participants |
| Bevacizumab (0.004 mg) | Distribution of VEGF Levels | Decrease in VEGF by 1% to <25% | 0 Participants |
| Bevacizumab (0.004 mg) | Distribution of VEGF Levels | Any increase in VEGF | 4 Participants |
| Bevacizumab (0.002 mg) | Distribution of VEGF Levels | Decrease in VEGF by 1% to <25% | 0 Participants |
| Bevacizumab (0.002 mg) | Distribution of VEGF Levels | Decrease in VEGF by 25% to <50% | 1 Participants |
| Bevacizumab (0.002 mg) | Distribution of VEGF Levels | Any increase in VEGF | 1 Participants |
| Bevacizumab (0.002 mg) | Distribution of VEGF Levels | Decrease in VEGF by greater than or equal to 50% | 3 Participants |
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
Time frame: 12-month corrected age
Population: Eyes, Seven enrolled study eyes and 11 enrolled fellow eyes missing from the table due to lack of 4-week follow-up, including death or deviation. Of these eyes, 5 study eyes and 4 fellow eyes were missing due to death. Eleven additional enrolled fellow eyes missing due to lack of need for initial injection.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Bevacizumab | Number of Fellow Eyes Requiring Additional Treatment/s for ROP | Additional Treatment Needed : Severe ROP: Late Reactivation | 2 Participants |
| Bevacizumab | Number of Fellow Eyes Requiring Additional Treatment/s for ROP | Additional Treatment Needed : Severe ROP: Early Reactivation | 0 Participants |
| Bevacizumab | Number of Fellow Eyes Requiring Additional Treatment/s for ROP | Additional Treatment Needed : Persistent Avascular Retina | 3 Participants |
| Bevacizumab | Number of Fellow Eyes Requiring Additional Treatment/s for ROP | Additional Treatment Needed : Severe ROP: Initial Treatment Failure | 0 Participants |
| Bevacizumab | Number of Fellow Eyes Requiring Additional Treatment/s for ROP | No Additional Treatment | 5 Participants |
| Bevacizumab (0.0125 mg) | Number of Fellow Eyes Requiring Additional Treatment/s for ROP | No Additional Treatment | 8 Participants |
| Bevacizumab (0.0125 mg) | Number of Fellow Eyes Requiring Additional Treatment/s for ROP | Additional Treatment Needed : Severe ROP: Late Reactivation | 3 Participants |
| Bevacizumab (0.0125 mg) | Number of Fellow Eyes Requiring Additional Treatment/s for ROP | Additional Treatment Needed : Severe ROP: Early Reactivation | 0 Participants |
| Bevacizumab (0.0125 mg) | Number of Fellow Eyes Requiring Additional Treatment/s for ROP | Additional Treatment Needed : Severe ROP: Initial Treatment Failure | 0 Participants |
| Bevacizumab (0.0125 mg) | Number of Fellow Eyes Requiring Additional Treatment/s for ROP | Additional Treatment Needed : Persistent Avascular Retina | 3 Participants |
| Bevacizumab (0.0625 mg) | Number of Fellow Eyes Requiring Additional Treatment/s for ROP | No Additional Treatment | 11 Participants |
| Bevacizumab (0.0625 mg) | Number of Fellow Eyes Requiring Additional Treatment/s for ROP | Additional Treatment Needed : Severe ROP: Early Reactivation | 0 Participants |
| Bevacizumab (0.0625 mg) | Number of Fellow Eyes Requiring Additional Treatment/s for ROP | Additional Treatment Needed : Severe ROP: Initial Treatment Failure | 3 Participants |
| Bevacizumab (0.0625 mg) | Number of Fellow Eyes Requiring Additional Treatment/s for ROP | Additional Treatment Needed : Severe ROP: Late Reactivation | 5 Participants |
| Bevacizumab (0.0625 mg) | Number of Fellow Eyes Requiring Additional Treatment/s for ROP | Additional Treatment Needed : Persistent Avascular Retina | 2 Participants |
| Bevacizumab (0.031 mg) | Number of Fellow Eyes Requiring Additional Treatment/s for ROP | No Additional Treatment | 4 Participants |
| Bevacizumab (0.031 mg) | Number of Fellow Eyes Requiring Additional Treatment/s for ROP | Additional Treatment Needed : Severe ROP: Initial Treatment Failure | 0 Participants |
| Bevacizumab (0.031 mg) | Number of Fellow Eyes Requiring Additional Treatment/s for ROP | Additional Treatment Needed : Severe ROP: Early Reactivation | 0 Participants |
| Bevacizumab (0.031 mg) | Number of Fellow Eyes Requiring Additional Treatment/s for ROP | Additional Treatment Needed : Severe ROP: Late Reactivation | 0 Participants |
| Bevacizumab (0.031 mg) | Number of Fellow Eyes Requiring Additional Treatment/s for ROP | Additional Treatment Needed : Persistent Avascular Retina | 2 Participants |
| Bevacizumab (0.016 mg) | Number of Fellow Eyes Requiring Additional Treatment/s for ROP | Additional Treatment Needed : Severe ROP: Initial Treatment Failure | 0 Participants |
| Bevacizumab (0.016 mg) | Number of Fellow Eyes Requiring Additional Treatment/s for ROP | Additional Treatment Needed : Severe ROP: Early Reactivation | 0 Participants |
| Bevacizumab (0.016 mg) | Number of Fellow Eyes Requiring Additional Treatment/s for ROP | Additional Treatment Needed : Persistent Avascular Retina | 7 Participants |
| Bevacizumab (0.016 mg) | Number of Fellow Eyes Requiring Additional Treatment/s for ROP | No Additional Treatment | 1 Participants |
| Bevacizumab (0.016 mg) | Number of Fellow Eyes Requiring Additional Treatment/s for ROP | Additional Treatment Needed : Severe ROP: Late Reactivation | 2 Participants |
| Bevacizumab (0.008 mg) | Number of Fellow Eyes Requiring Additional Treatment/s for ROP | Additional Treatment Needed : Severe ROP: Late Reactivation | 2 Participants |
| Bevacizumab (0.008 mg) | Number of Fellow Eyes Requiring Additional Treatment/s for ROP | No Additional Treatment | 3 Participants |
| Bevacizumab (0.008 mg) | Number of Fellow Eyes Requiring Additional Treatment/s for ROP | Additional Treatment Needed : Severe ROP: Early Reactivation | 0 Participants |
| Bevacizumab (0.008 mg) | Number of Fellow Eyes Requiring Additional Treatment/s for ROP | Additional Treatment Needed : Persistent Avascular Retina | 2 Participants |
| Bevacizumab (0.008 mg) | Number of Fellow Eyes Requiring Additional Treatment/s for ROP | Additional Treatment Needed : Severe ROP: Initial Treatment Failure | 1 Participants |
| Bevacizumab (0.004 mg) | Number of Fellow Eyes Requiring Additional Treatment/s for ROP | Additional Treatment Needed : Severe ROP: Initial Treatment Failure | 2 Participants |
| Bevacizumab (0.004 mg) | Number of Fellow Eyes Requiring Additional Treatment/s for ROP | Additional Treatment Needed : Severe ROP: Late Reactivation | 2 Participants |
| Bevacizumab (0.004 mg) | Number of Fellow Eyes Requiring Additional Treatment/s for ROP | Additional Treatment Needed : Severe ROP: Early Reactivation | 0 Participants |
| Bevacizumab (0.004 mg) | Number of Fellow Eyes Requiring Additional Treatment/s for ROP | No Additional Treatment | 5 Participants |
| Bevacizumab (0.004 mg) | Number of Fellow Eyes Requiring Additional Treatment/s for ROP | Additional Treatment Needed : Persistent Avascular Retina | 2 Participants |
| Bevacizumab (0.002 mg) | Number of Fellow Eyes Requiring Additional Treatment/s for ROP | Additional Treatment Needed : Severe ROP: Early Reactivation | 1 Participants |
| Bevacizumab (0.002 mg) | Number of Fellow Eyes Requiring Additional Treatment/s for ROP | No Additional Treatment | 6 Participants |
| Bevacizumab (0.002 mg) | Number of Fellow Eyes Requiring Additional Treatment/s for ROP | Additional Treatment Needed : Severe ROP: Initial Treatment Failure | 1 Participants |
| Bevacizumab (0.002 mg) | Number of Fellow Eyes Requiring Additional Treatment/s for ROP | Additional Treatment Needed : Severe ROP: Late Reactivation | 2 Participants |
| Bevacizumab (0.002 mg) | Number of Fellow Eyes Requiring Additional Treatment/s for ROP | Additional Treatment Needed : Persistent Avascular Retina | 8 Participants |
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
Time frame: Enrollment to 12-month corrected age
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Bevacizumab | Number of Infant Deaths | 0 Participants |
| Bevacizumab (0.0125 mg) | Number of Infant Deaths | 2 Participants |
| Bevacizumab (0.0625 mg) | Number of Infant Deaths | 2 Participants |
| Bevacizumab (0.031 mg) | Number of Infant Deaths | 2 Participants |
| Bevacizumab (0.016 mg) | Number of Infant Deaths | 1 Participants |
| Bevacizumab (0.008 mg) | Number of Infant Deaths | 0 Participants |
| Bevacizumab (0.004 mg) | Number of Infant Deaths | 0 Participants |
| Bevacizumab (0.002 mg) | Number of Infant Deaths | 1 Participants |
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.
Time frame: 24-month corrected age
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Bevacizumab | Number of Infants With 24-Month Extended Follow Up Exam | 6 Participants |
| Bevacizumab (0.0125 mg) | Number of Infants With 24-Month Extended Follow Up Exam | 8 Participants |
| Bevacizumab (0.0625 mg) | Number of Infants With 24-Month Extended Follow Up Exam | 15 Participants |
| Bevacizumab (0.031 mg) | Number of Infants With 24-Month Extended Follow Up Exam | 7 Participants |
| Bevacizumab (0.016 mg) | Number of Infants With 24-Month Extended Follow Up Exam | 11 Participants |
| Bevacizumab (0.008 mg) | Number of Infants With 24-Month Extended Follow Up Exam | 6 Participants |
| Bevacizumab (0.004 mg) | Number of Infants With 24-Month Extended Follow Up Exam | 5 Participants |
| Bevacizumab (0.002 mg) | Number of Infants With 24-Month Extended Follow Up Exam | 12 Participants |
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
Time frame: 12-month corrected age
Population: Eyes, Seven enrolled study eyes and 11 enrolled fellow eyes missing from the table due to lack of 4-week follow-up, including death or deviation. Of these eyes, 5 study eyes and 4 fellow eyes were missing due to death. Eleven additional enrolled fellow eyes missing due to lack of need for initial injection.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Bevacizumab | Number of Study Eyes Requiring Additional Treatment/s for ROP | Additional Treatment Needed : Severe ROP: Initial Treatment Failure | 0 Participants |
| Bevacizumab | Number of Study Eyes Requiring Additional Treatment/s for ROP | No Additional Treatment | 6 Participants |
| Bevacizumab | Number of Study Eyes Requiring Additional Treatment/s for ROP | Additional Treatment Needed : Persistent Avascular Retina | 3 Participants |
| Bevacizumab | Number of Study Eyes Requiring Additional Treatment/s for ROP | Additional Treatment Needed : Severe ROP: Late Reactivation | 2 Participants |
| Bevacizumab | Number of Study Eyes Requiring Additional Treatment/s for ROP | Additional Treatment Needed : Severe ROP: Early Reactivation | 0 Participants |
| Bevacizumab (0.0125 mg) | Number of Study Eyes Requiring Additional Treatment/s for ROP | Additional Treatment Needed : Severe ROP: Early Reactivation | 0 Participants |
| Bevacizumab (0.0125 mg) | Number of Study Eyes Requiring Additional Treatment/s for ROP | Additional Treatment Needed : Persistent Avascular Retina | 2 Participants |
| Bevacizumab (0.0125 mg) | Number of Study Eyes Requiring Additional Treatment/s for ROP | No Additional Treatment | 8 Participants |
| Bevacizumab (0.0125 mg) | Number of Study Eyes Requiring Additional Treatment/s for ROP | Additional Treatment Needed : Severe ROP: Late Reactivation | 4 Participants |
| Bevacizumab (0.0125 mg) | Number of Study Eyes Requiring Additional Treatment/s for ROP | Additional Treatment Needed : Severe ROP: Initial Treatment Failure | 0 Participants |
| Bevacizumab (0.0625 mg) | Number of Study Eyes Requiring Additional Treatment/s for ROP | Additional Treatment Needed : Severe ROP: Early Reactivation | 0 Participants |
| Bevacizumab (0.0625 mg) | Number of Study Eyes Requiring Additional Treatment/s for ROP | No Additional Treatment | 13 Participants |
| Bevacizumab (0.0625 mg) | Number of Study Eyes Requiring Additional Treatment/s for ROP | Additional Treatment Needed : Severe ROP: Initial Treatment Failure | 3 Participants |
| Bevacizumab (0.0625 mg) | Number of Study Eyes Requiring Additional Treatment/s for ROP | Additional Treatment Needed : Persistent Avascular Retina | 3 Participants |
| Bevacizumab (0.0625 mg) | Number of Study Eyes Requiring Additional Treatment/s for ROP | Additional Treatment Needed : Severe ROP: Late Reactivation | 5 Participants |
| Bevacizumab (0.031 mg) | Number of Study Eyes Requiring Additional Treatment/s for ROP | Additional Treatment Needed : Severe ROP: Late Reactivation | 0 Participants |
| Bevacizumab (0.031 mg) | Number of Study Eyes Requiring Additional Treatment/s for ROP | No Additional Treatment | 6 Participants |
| Bevacizumab (0.031 mg) | Number of Study Eyes Requiring Additional Treatment/s for ROP | Additional Treatment Needed : Severe ROP: Initial Treatment Failure | 0 Participants |
| Bevacizumab (0.031 mg) | Number of Study Eyes Requiring Additional Treatment/s for ROP | Additional Treatment Needed : Severe ROP: Early Reactivation | 0 Participants |
| Bevacizumab (0.031 mg) | Number of Study Eyes Requiring Additional Treatment/s for ROP | Additional Treatment Needed : Persistent Avascular Retina | 3 Participants |
| Bevacizumab (0.016 mg) | Number of Study Eyes Requiring Additional Treatment/s for ROP | Additional Treatment Needed : Severe ROP: Late Reactivation | 4 Participants |
| Bevacizumab (0.016 mg) | Number of Study Eyes Requiring Additional Treatment/s for ROP | Additional Treatment Needed : Severe ROP: Initial Treatment Failure | 0 Participants |
| Bevacizumab (0.016 mg) | Number of Study Eyes Requiring Additional Treatment/s for ROP | Additional Treatment Needed : Severe ROP: Early Reactivation | 0 Participants |
| Bevacizumab (0.016 mg) | Number of Study Eyes Requiring Additional Treatment/s for ROP | Additional Treatment Needed : Persistent Avascular Retina | 8 Participants |
| Bevacizumab (0.016 mg) | Number of Study Eyes Requiring Additional Treatment/s for ROP | No Additional Treatment | 1 Participants |
| Bevacizumab (0.008 mg) | Number of Study Eyes Requiring Additional Treatment/s for ROP | Additional Treatment Needed : Severe ROP: Late Reactivation | 3 Participants |
| Bevacizumab (0.008 mg) | Number of Study Eyes Requiring Additional Treatment/s for ROP | Additional Treatment Needed : Persistent Avascular Retina | 2 Participants |
| Bevacizumab (0.008 mg) | Number of Study Eyes Requiring Additional Treatment/s for ROP | Additional Treatment Needed : Severe ROP: Early Reactivation | 0 Participants |
| Bevacizumab (0.008 mg) | Number of Study Eyes Requiring Additional Treatment/s for ROP | Additional Treatment Needed : Severe ROP: Initial Treatment Failure | 0 Participants |
| Bevacizumab (0.008 mg) | Number of Study Eyes Requiring Additional Treatment/s for ROP | No Additional Treatment | 4 Participants |
| Bevacizumab (0.004 mg) | Number of Study Eyes Requiring Additional Treatment/s for ROP | Additional Treatment Needed : Severe ROP: Late Reactivation | 3 Participants |
| Bevacizumab (0.004 mg) | Number of Study Eyes Requiring Additional Treatment/s for ROP | Additional Treatment Needed : Severe ROP: Initial Treatment Failure | 1 Participants |
| Bevacizumab (0.004 mg) | Number of Study Eyes Requiring Additional Treatment/s for ROP | Additional Treatment Needed : Severe ROP: Early Reactivation | 0 Participants |
| Bevacizumab (0.004 mg) | Number of Study Eyes Requiring Additional Treatment/s for ROP | No Additional Treatment | 5 Participants |
| Bevacizumab (0.004 mg) | Number of Study Eyes Requiring Additional Treatment/s for ROP | Additional Treatment Needed : Persistent Avascular Retina | 1 Participants |
| Bevacizumab (0.002 mg) | Number of Study Eyes Requiring Additional Treatment/s for ROP | No Additional Treatment | 8 Participants |
| Bevacizumab (0.002 mg) | Number of Study Eyes Requiring Additional Treatment/s for ROP | Additional Treatment Needed : Persistent Avascular Retina | 9 Participants |
| Bevacizumab (0.002 mg) | Number of Study Eyes Requiring Additional Treatment/s for ROP | Additional Treatment Needed : Severe ROP: Initial Treatment Failure | 2 Participants |
| Bevacizumab (0.002 mg) | Number of Study Eyes Requiring Additional Treatment/s for ROP | Additional Treatment Needed : Severe ROP: Late Reactivation | 0 Participants |
| Bevacizumab (0.002 mg) | Number of Study Eyes Requiring Additional Treatment/s for ROP | Additional Treatment Needed : Severe ROP: Early Reactivation | 4 Participants |
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
Time frame: Enrollment to 12-month corrected age
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Bevacizumab | Proportion of Infants for Whom at Least One Event Was Reported | 6 Participants |
| Bevacizumab (0.0125 mg) | Proportion of Infants for Whom at Least One Event Was Reported | 4 Participants |
| Bevacizumab (0.0625 mg) | Proportion of Infants for Whom at Least One Event Was Reported | 5 Participants |
| Bevacizumab (0.031 mg) | Proportion of Infants for Whom at Least One Event Was Reported | 1 Participants |
| Bevacizumab (0.016 mg) | Proportion of Infants for Whom at Least One Event Was Reported | 5 Participants |
| Bevacizumab (0.008 mg) | Proportion of Infants for Whom at Least One Event Was Reported | 1 Participants |
| Bevacizumab (0.004 mg) | Proportion of Infants for Whom at Least One Event Was Reported | 5 Participants |
| Bevacizumab (0.002 mg) | Proportion of Infants for Whom at Least One Event Was Reported | 11 Participants |
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
Time frame: Enrollment to 12-month corrected age
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Bevacizumab | Proportion of Infants With an Adverse Event Thought by Investigator to be Related to Study Drug | 0 Participants |
| Bevacizumab (0.0125 mg) | Proportion of Infants With an Adverse Event Thought by Investigator to be Related to Study Drug | 0 Participants |
| Bevacizumab (0.0625 mg) | Proportion of Infants With an Adverse Event Thought by Investigator to be Related to Study Drug | 0 Participants |
| Bevacizumab (0.031 mg) | Proportion of Infants With an Adverse Event Thought by Investigator to be Related to Study Drug | 0 Participants |
| Bevacizumab (0.016 mg) | Proportion of Infants With an Adverse Event Thought by Investigator to be Related to Study Drug | 1 Participants |
| Bevacizumab (0.008 mg) | Proportion of Infants With an Adverse Event Thought by Investigator to be Related to Study Drug | 1 Participants |
| Bevacizumab (0.004 mg) | Proportion of Infants With an Adverse Event Thought by Investigator to be Related to Study Drug | 0 Participants |
| Bevacizumab (0.002 mg) | Proportion of Infants With an Adverse Event Thought by Investigator to be Related to Study Drug | 0 Participants |
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
Time frame: 12-month corrected age
Population: 8 Infants died before exam, exam not completed for 5 participants, and 16 patients were lost to follow up and did not complete.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Bevacizumab | Visual Fixation Status at 12 Months | Central Fixation in Both Eyes | 9 Participants |
| Bevacizumab | Visual Fixation Status at 12 Months | No Central Fixation in either eye | 1 Participants |
| Bevacizumab | Visual Fixation Status at 12 Months | Central Fixation in One Eye | 0 Participants |
| Bevacizumab (0.0125 mg) | Visual Fixation Status at 12 Months | No Central Fixation in either eye | 0 Participants |
| Bevacizumab (0.0125 mg) | Visual Fixation Status at 12 Months | Central Fixation in One Eye | 0 Participants |
| Bevacizumab (0.0125 mg) | Visual Fixation Status at 12 Months | Central Fixation in Both Eyes | 13 Participants |
| Bevacizumab (0.0625 mg) | Visual Fixation Status at 12 Months | No Central Fixation in either eye | 0 Participants |
| Bevacizumab (0.0625 mg) | Visual Fixation Status at 12 Months | Central Fixation in Both Eyes | 16 Participants |
| Bevacizumab (0.0625 mg) | Visual Fixation Status at 12 Months | Central Fixation in One Eye | 0 Participants |
| Bevacizumab (0.031 mg) | Visual Fixation Status at 12 Months | Central Fixation in Both Eyes | 6 Participants |
| Bevacizumab (0.031 mg) | Visual Fixation Status at 12 Months | Central Fixation in One Eye | 0 Participants |
| Bevacizumab (0.031 mg) | Visual Fixation Status at 12 Months | No Central Fixation in either eye | 0 Participants |
| Bevacizumab (0.016 mg) | Visual Fixation Status at 12 Months | Central Fixation in One Eye | 0 Participants |
| Bevacizumab (0.016 mg) | Visual Fixation Status at 12 Months | Central Fixation in Both Eyes | 11 Participants |
| Bevacizumab (0.016 mg) | Visual Fixation Status at 12 Months | No Central Fixation in either eye | 2 Participants |
| Bevacizumab (0.008 mg) | Visual Fixation Status at 12 Months | Central Fixation in One Eye | 0 Participants |
| Bevacizumab (0.008 mg) | Visual Fixation Status at 12 Months | Central Fixation in Both Eyes | 8 Participants |
| Bevacizumab (0.008 mg) | Visual Fixation Status at 12 Months | No Central Fixation in either eye | 0 Participants |
| Bevacizumab (0.004 mg) | Visual Fixation Status at 12 Months | Central Fixation in One Eye | 0 Participants |
| Bevacizumab (0.004 mg) | Visual Fixation Status at 12 Months | Central Fixation in Both Eyes | 10 Participants |
| Bevacizumab (0.004 mg) | Visual Fixation Status at 12 Months | No Central Fixation in either eye | 0 Participants |
| Bevacizumab (0.002 mg) | Visual Fixation Status at 12 Months | Central Fixation in Both Eyes | 12 Participants |
| Bevacizumab (0.002 mg) | Visual Fixation Status at 12 Months | Central Fixation in One Eye | 1 Participants |
| Bevacizumab (0.002 mg) | Visual Fixation Status at 12 Months | No Central Fixation in either eye | 2 Participants |