Study to Assess the Efficacy, Safety, and Tolerability of Intravitreal Aflibercept Compared to Laser Photocoagulation in Patients With Retinopathy of Prematurity (BUTTERFLEYE)

July 19, 2023 updated by: Regeneron Pharmaceuticals

Randomized, Controlled, Multi-Center Study to Assess the Efficacy, Safety, and Tolerability of Intravitreal Aflibercept Compared to Laser Photocoagulation in Patients With Retinopathy of Prematurity

The primary objective of the study is to assess the efficacy of aflibercept compared to laser in patients diagnosed with retinopathy of prematurity (ROP). The secondary objectives of the study are to assess the need for a second treatment modality, to assess the recurrence of ROP in the study and to assess the safety and tolerability of aflibercept.

Study Overview

Study Type

Interventional

Enrollment (Actual)

127

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Sofia, Bulgaria, 1407
        • Regeneron Study Site
      • Sofia, Bulgaria, 1504
        • Regeneron Study Site
      • Varna, Bulgaria, 9002
        • Regeneron Study Site
    • Antioquia
      • Medellin, Antioquia, Colombia, 50034
        • Regeneron Study Site
    • Santander
      • Floridablanca, Santander, Colombia, 681004
        • Regeneron Study Site
      • Ostrava-Poruba, Czechia, 708 52
        • Regeneron Study Site
      • Debrecen, Hungary, H-4032
        • Regeneron Study Site
      • Cheonan, Korea, Republic of, 31151
        • Regeneron Study Site
      • Iași, Romania, 700038
        • Regeneron Study Site
      • Moscow, Russian Federation, 119620
        • Regeneron Study Site
      • Moscow, Russian Federation, 119571
        • Regeneron Study Site
    • Sankt-Peterburg
      • Saint-Petersburg, Sankt-Peterburg, Russian Federation, 194100
        • Regeneron Study Site
      • Bratislava, Slovakia, 833 40
        • Regeneron Study Site
      • Kaohsiung, Taiwan, 81346
        • Regeneron Study Site
      • Khon Kaen, Thailand, 40002
        • Regeneron Study Site
    • Bangkok
      • Pathum Wan, Bangkok, Thailand, 10330
        • Regeneron Study Site
      • Ratchathewi, Bangkok, Thailand, 10400
        • Regeneron Study Site
    • Chiang Mai
      • Chiangmai, Chiang Mai, Thailand, 50200
        • Regeneron Study Site
    • Songkhla
      • Hat Yai, Songkhla, Thailand, 90110
        • Regeneron Study Site
      • Adana, Turkey, 4522
        • Regeneron Study Site
      • Ankara, Turkey, 06560
        • Regeneron Study Site
      • Ankara, Turkey, 06100
        • Regeneron Study Site
      • Eskisehir, Turkey, 26480
        • Regeneron Study Site
    • Arizona
      • Phoenix, Arizona, United States, 85016
        • Regeneron Study Site
    • California
      • La Jolla, California, United States, 92093
        • Regeneron Study Site
      • Loma Linda, California, United States, 92354
        • Regeneron Study Site
      • Orange, California, United States, 92868
        • Regeneron Study Site
      • Palo Alto, California, United States, 94303
        • Regeneron Study Site
      • San Diego, California, United States, 92123
        • Regeneron Study Site
      • San Francisco, California, United States, 94143
        • Regeneron Study Site
    • Florida
      • Gainesville, Florida, United States, 32608
        • Regeneron Study Site
    • Georgia
      • Augusta, Georgia, United States, 78705
        • Regeneron Study Site
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Regeneron Study Site
    • Massachusetts
      • Boston, Massachusetts, United States, 02111
        • Regeneron Study Site
    • Michigan
      • Ann Arbor, Michigan, United States, 48105
        • Regeneron Study Site
      • Royal Oak, Michigan, United States, 48073
        • Regeneron Study Site
    • New York
      • Bronx, New York, United States, 10462
        • Regeneron Study Site
      • Brooklyn, New York, United States, 11203
        • Regeneron Study Site
      • Brooklyn, New York, United States, 11213
        • Regeneron Study Site
      • Buffalo, New York, United States, 14209
        • Regeneron Study Site
      • New York, New York, United States, 10029
        • Regeneron Study Site
      • New York, New York, United States, 10017
        • Regeneron Study Site
      • Valhalla, New York, United States, 10595
        • Regeneron Study Site
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • Regeneron Study Site
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Regeneron Study Site
    • Rhode Island
      • Providence, Rhode Island, United States, 02905
        • Regeneron Study Site
    • Texas
      • Austin, Texas, United States, 78705
        • Regeneron Study Site
      • San Antonio, Texas, United States, 78229
        • Regeneron Study Site
      • San Antonio, Texas, United States, 78240
        • Regeneron Study Site
    • West Virginia
      • Morgantown, West Virginia, United States, 26506
        • Regeneron Study Site
      • Ho Chi Minh, Vietnam, 70000
        • Regeneron Study Site
      • Hue, Vietnam, 100000
        • Regeneron Study Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Key Inclusion Criteria:

  • Gestational age at birth ≤ 32 weeks or birth weight ≤1500 g
  • Patients with treatment-naïve retinopathy of prematurity (ROP) classified according to the International Classification for ROP in at least one eye as:

    • Zone I Stage 1 plus, or 2 plus, or 3 non-plus or 3 plus, or
    • Zone II Stage 2 plus or 3 plus, or
    • Aggressive posterior retinopathy of prematurity (AP-ROP)

Key Exclusion Criteria:

  • Known or suspected chromosomal abnormality, genetic disorder, or syndrome
  • Previous exposure to any Intravitreal (IVT) or systemic anti-vascular endothelial growth factor (VEGF) agent, including maternal exposure during pregnancy and/or during breastfeeding
  • Clinically significant neurological disease (eg, intraventricular hemorrhage grade 3 or higher, periventricular leukomalacia, congenital brain lesions significantly impairing optic nerve function, severe hydrocephalus with significantly increased intracranial pressure)
  • Pediatric conditions rendering the infant ineligible for study intervention at baseline or for repeated blood draws as evaluated by a neonatal intensive care unit specialist and a study ophthalmologist
  • Presence of active ocular infection within 5 days of the first treatment
  • Advanced stages of ROP with partial or complete retinal detachment (ROP stage 4 and stage 5)
  • ROP involving only Zone III

NOTE: Other protocol defined inclusion/exclusion criteria apply.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Aflibercept Group
Patients will receive a single intravitreal (IVT) injection per eligible eye at baseline.
Administered IVT
Other Names:
  • BAY86-5321
  • EYLEA®
  • REGN3
  • VEGF trap-eye
Experimental: Laser Group
Patients will undergo laser treatment in each eligible eye at baseline.
Transpupillary conventional laser will be administered according to standard local procedures.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Absence of Active Retinopathy of Prematurity (ROP) and Unfavorable Structural Outcomes From Baseline to Week 52 of Chronological Age
Time Frame: Baseline to week 52 of chronological age
Active ROP was ROP requiring treatment and unfavorable structural outcome was defined as retinal detachment, macular dragging, macular fold, or retrolental opacity. For participants with both eyes enrolled in the study, both eyes must have met the endpoint. Participants with only one study eye enrolled were responders if the respective eye responded.
Baseline to week 52 of chronological age

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants Requiring Intervention With a Second Treatment Modality From Baseline to Week 52 of Chronological Age
Time Frame: Baseline to to week 52 of chronological age
Second treatment modality includes any treatment in addition to that assigned to the participant at baseline. This includes per-protocol rescue treatment (laser for aflibercept group, aflibercept for laser group), anti-VEGF agents not part of study protocol (e.g., bevacizumab, ranibizumab, commercially-available aflibercept not provided as study medication), or any ocular surgery for the management of any retinal pathology secondary to ROP (e.g., victrectomy, scleral buckle for retinal detachments).
Baseline to to week 52 of chronological age
Percentage of Participants With Recurrence of ROP Through Week 52 of Chronological Age
Time Frame: Baseline to week 52 of chronological age
Recurrence of disease is defined as the reappearance of the disease requiring further treatment (including retreatment or rescue), where both "presence of ROP" and "presence of active ROP requiring treatment" are marked as "Yes", after initial regression. Here, the initial regression is defined as, at a particular visit, absence of ROP or ROP treatment not required for active ROP, i.e., presence of ROP is marked as "No" or the presence of active ROP requiring treatment is marked as "No."
Baseline to week 52 of chronological age
Percentage of Participants With Ocular Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
Time Frame: Baseline to Week 52 of chronological age
Baseline to Week 52 of chronological age
Percentage of Participants With Systematic (Non-ocular) TEAEs and TESAEs
Time Frame: Baseline to Week 52 of chronological age
Baseline to Week 52 of chronological age

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 30, 2019

Primary Completion (Actual)

August 18, 2022

Study Completion (Actual)

August 18, 2022

Study Registration Dates

First Submitted

September 23, 2019

First Submitted That Met QC Criteria

September 23, 2019

First Posted (Actual)

September 24, 2019

Study Record Updates

Last Update Posted (Actual)

July 20, 2023

Last Update Submitted That Met QC Criteria

July 19, 2023

Last Verified

July 1, 2023

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing

IPD Sharing Time Frame

Individual anonymized participant data will be considered for sharing once the indication has been approved by a regulatory body, if there is legal authority to share the data and there is not a reasonable likelihood of participant re-identification.

IPD Sharing Access Criteria

Qualified researchers may request access to anonymized patient level data or aggregate study data when Regeneron has received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc) for the product and indication, has the legal authority to share the data, and has made the study results publicly available (eg, scientific publication, scientific conference, clinical trial registry).

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • ANALYTIC_CODE
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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