Bevacizumab Treatment For Posterior Zone I ROP (ROP4)

• ClinicalTrials.gov Identifier: NCT04634578
• Recruitment Status: Recruiting
• First Posted: November 18, 2020
• Last Update Posted: October 19, 2022
• Sponsor: Jaeb Center for Health Research
• Collaborators: Pediatric Eye Disease Investigator Group; National Eye Institute (NEI)
• Information provided by (Responsible Party): Jaeb Center for Health Research

Tracking Information

• First Submitted Date: November 16, 2020
• First Posted Date: November 18, 2020
• Last Update Posted Date: October 19, 2022
• Actual Study Start Date: May 18, 2022
• Estimated Primary Completion Date: December 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 16, 2020)

Treatment Success at 4 Weeks Post Injection [ Time Frame: 4 weeks ]

Treatment success, determined at 4 weeks, post injection, and meeting all the following criteria:

• Improvement by the 4-day exam (3 to 5 days)
• No recurrence of type 1 ROP or severe neovascularization requiring additional treatment within 4 weeks of injection.

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Bevacizumab Treatment For Posterior Zone I ROP
• Official Title: Bevacizumab Treatment For Posterior Zone I Retinopathy of Prematurity
• Brief Summary: Type 1 retinopathy of prematurity in zone I represents the most severe type of ROP and has the worst prognosis. It is unknown whether low-dose bevacizumab will be successful in these severe cases. Also unknown is the timing and extent of peripheral retinal vascularization after low-dose bevacizumab compared with the standard dose. The current study will evaluate whether doses of 0.063 mg and 0.25mg are effective as treatment for type 1 ROP, with ROP and retinal vessels all in zone I.
• Detailed Description: Infants with type 1 ROP and no prior treatment for ROP will be randomly assigned (1:1) to treatment with either intravitreous bevacizumab 0.063 mg or either intravitreous bevacizumab 0.25 mg. Study exams will be at 1 day, 4 days (if no improvement on day 1), 1, 2, 3, and 4 weeks, and at 2 and 4-months post-treatment (and re-treatment when indicated). Additional study exams will occur at adjusted age 6 and 12 months. Non-study examinations will be at clinician discretion and are likely to occur more often. The primary outcome will be treatment success within each dose group, defined as improvement by the day 4 exam and no recurrence of type 1 ROP or severe neovascularization requiring additional treatment within 4 weeks of injection. Important secondary outcomes include safety and efficacy. refractive outcomes, and the extent of retinal vascularization at 2 and 4 months post-injection between the two dose groups.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Retinopathy of Prematurity

Intervention

Drug: Bevacizumab

All participants will receive a single intravitreal injection of bevacizumab in one or both eyes following enrollment into the study. The injection/s should be given as soon as possible but no later than 2 days after the diagnosis of type 1 ROP meeting all of the inclusion criteria and none of the exclusion criteria.

Eyes meeting eligibility criteria will receive a single dose of 0.063 mg or 0.25mg bevacizumab provided by the pharmacy at the investigator's institution.

Other Name: Avastin

Study Arms

• Experimental: Bevacizumab- 0.063 mg
  Participants will receive a single intravitreal injection of 0.063 mg of bevacizumab in one or both eyes following enrollment into the study. The injection/s should be given as soon as possible but no later than 2 days after the diagnosis of type 1 ROP meeting all of the inclusion criteria and none of the exclusion criteria.
  Intervention: Drug: Bevacizumab
• Experimental: Bevacizumab- 0.25 mg
  Participants will receive a single intravitreal injection of 0.25 mg of bevacizumab in one or both eyes following enrollment into the study. The injection/s should be given as soon as possible but no later than 2 days after the diagnosis of type 1 ROP meeting all of the inclusion criteria and none of the exclusion criteria.
  Intervention: Drug: Bevacizumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 16, 2020): 80
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 2024
• Estimated Primary Completion Date: December 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

The study participant must have at least one eye meeting all of the inclusion criteria in order to be eligible to participate:

1. Birth weight < 1251 grams
2. Newly diagnosed (within 2 days) type 1 ROP in zone I in one or both eyes

Exclusion Criteria:

Participants meeting any of the following exclusion criteria will be excluded from study participation.

1. Previous treatment for ROP
2. Stage 4 or 5 ROP in either eye
3. Treatment could not be done within 2 days of diagnosis of type 1 ROP
4. Investigator unwilling to randomize or parent unwilling to accept randomized assignment to either treatment
5. Transfer to another hospital anticipated within the next 4 weeks where exams by study-certified examiners are not available. If hospital discharge is anticipated within the next 4 weeks, parents unable or unwilling to return to the PEDIG site for outpatient follow-up visits.
6. Active ocular infection or purulent nasolacrimal duct obstruction in either eye

One eye will be excluded, and other eye may be eligible, if either of the following are present:

• Visually significant ocular anomaly (e.g., cataract, coloboma)
• Opacity that precludes an adequate view of the retina

Sex/Gender

• Sexes Eligible for Study: All

• Ages: up to 6 Months (Child)
• Accepts Healthy Volunteers: No

Contacts

Contact: Raymond T Kraker, MSPH; 8139758690; rkraker@jaeb.org

Contact: Brooke P Fimbel; 8139758690; bfimbel@jaeb.org

• Listed Location Countries: Canada, United States

Administrative Information

• NCT Number: NCT04634578
• Other Study ID Numbers: ROP4; UG1EY011751 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

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 Pediatric Eye Disease Investigator Group (PEDIG) public website after the completion of each protocol and publication of the primary manuscript.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Time Frame: Data will be made available after publication of each primary manuscript.
• Access Criteria: Users accessing the data must enter an email address.

• Current Responsible Party: Jaeb Center for Health Research
• Original Responsible Party: Same as current
• Current Study Sponsor: Jaeb Center for Health Research
• Original Study Sponsor: Same as current

Collaborators

• Pediatric Eye Disease Investigator Group
• National Eye Institute (NEI)

Investigators

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

• PRS Account: Jaeb Center for Health Research
• Verification Date: October 2022