Clinical trial NCT02390531: Phase 1 Trial of Bevacizumab Treatment for Severe Retinopathy of Prematurity
Official title: Phase 1 Trial of Bevacizumab Treatment for Severe Retinopathy of Prematurity
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Retinopathy of Prematurity
Keywords: Retinopathy of Prematurity
Bevacizumab
ROP
Lead sponsor: Jaeb Center for Health Research
Sponsor class: OTHER
Collaborators: name: Pediatric Eye Disease Investigator Group
name: National Eye Institute (NEI)
First posted: 2015-03-17
Enrollment: 120
Sex: ALL
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
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
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Successful Treatment of ROP
timeFrame: 4 weeks post-injection
Secondary outcomes:
measure: Distribution of VEGF Levels
timeFrame: 2 weeks post-injection
measure: Distribution of VEGF Levels
timeFrame: 4 weeks post-injection
measure: Distribution of Avastin Levels
timeFrame: 2 weeks post-injection
measure: Distribution of Avastin Levels
timeFrame: 4 weeks post-injection
measure: Number of Study Eyes Requiring Additional Treatment/s for ROP
timeFrame: 12-month corrected age
measure: Any Adverse Events or Complications Since the 4-week Exam
timeFrame: 12-month corrected age
measure: Visual Fixation Status at 12 Months
timeFrame: 12-month corrected age
measure: Proportion of Infants for Whom at Least One Event Was Reported
timeFrame: Enrollment to 12-month corrected age
measure: Proportion of Infants With an Adverse Event Thought by Investigator to be Related to Study Drug
timeFrame: Enrollment to 12-month corrected age
measure: Count of Infants for Whom at Least One Serious Adverse Event Was Reported
timeFrame: Enrollment to 12-month corrected age
measure: Number of Infant Deaths
timeFrame: Enrollment to 12-month corrected age
measure: Number of Infants With 24-Month Extended Follow Up Exam
timeFrame: 24-month corrected age
measure: Number of Fellow Eyes Requiring Additional Treatment/s for ROP
timeFrame: 12-month corrected age
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: The Emory Eye Center
state: Georgia
city: Indianapolis
country: United States
facility: Riley Hospital for Children
state: Indiana
city: Baltimore
country: United States
facility: Wilmer Institute
state: Maryland
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Durham
country: United States
facility: Duke University Eye Center
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital
state: Ohio
city: Columbus
country: United States
facility: Pediatric Ophthalmology Associates, Inc.
state: Ohio
city: Oklahoma City
country: United States
facility: Dean A. McGee Eye Institute, University of Oklahoma
state: Oklahoma
city: Houston
country: United States
facility: Texas Children's Hospital - Dept. Of Ophthalmology
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Moran Eye Center
state: Utah
city: Norfolk
country: United States
facility: Virginia Pediatric Eye Center
state: Virginia
Study officials:
affiliation: Indiana University
name: David K Wallace, MD, MPH
role: STUDY_CHAIR
References:
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.
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.
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 Additional Treatments. Ophthalmology. 2018 Dec;125(12):1961-1966. doi: 10.1016/j.ophtha.2018.05.001. Epub 2018 Jun 7.
citation: 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.
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 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.