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

Primary Purpose

Retinopathy of Prematurity

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
aflibercept
laser photocoagulation
Sponsored by
Regeneron Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Retinopathy of Prematurity

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Regeneron Study Site
  • Regeneron Study Site
  • Regeneron Study Site
  • Regeneron Study Site
  • Regeneron Study Site
  • Regeneron Study Site
  • Regeneron Study Site
  • Regeneron Study Site
  • Regeneron Study Site
  • Regeneron Study Site
  • Regeneron Study Site
  • Regeneron Study Site
  • Regeneron Study Site
  • Regeneron Study Site
  • Regeneron Study Site
  • Regeneron Study Site
  • Regeneron Study Site
  • Regeneron Study Site
  • Regeneron Study Site
  • Regeneron Study Site
  • Regeneron Study Site
  • Regeneron Study Site
  • Regeneron Study Site
  • Regeneron Study Site
  • Regeneron Study Site
  • Regeneron Study Site
  • Regeneron Study Site
  • Regeneron Study Site
  • Regeneron Study Site
  • Regeneron Study Site
  • Regeneron Study Site
  • Regeneron Study Site
  • Regeneron Study Site
  • Regeneron Study Site
  • Regeneron Study Site
  • Regeneron Study Site
  • Regeneron Study Site
  • Regeneron Study Site
  • Regeneron Study Site
  • Regeneron Study Site
  • Regeneron Study Site
  • Regeneron Study Site
  • Regeneron Study Site
  • Regeneron Study Site
  • Regeneron Study Site
  • Regeneron Study Site
  • Regeneron Study Site
  • Regeneron Study Site
  • Regeneron Study Site
  • Regeneron Study Site
  • Regeneron Study Site
  • Regeneron Study Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Aflibercept Group

Laser Group

Arm Description

Patients will receive a single intravitreal (IVT) injection per eligible eye at baseline.

Patients will undergo laser treatment in each eligible eye at baseline.

Outcomes

Primary Outcome Measures

Percentage of Participants With Absence of Active Retinopathy of Prematurity (ROP) and Unfavorable Structural Outcomes From 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.

Secondary Outcome Measures

Percentage of Participants Requiring Intervention With a Second Treatment Modality From Baseline 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).
Percentage of Participants With Recurrence of ROP Through 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."
Percentage of Participants With Ocular Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
Percentage of Participants With Systematic (Non-ocular) TEAEs and TESAEs

Full Information

First Posted
September 23, 2019
Last Updated
July 19, 2023
Sponsor
Regeneron Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT04101721
Brief Title
Study to Assess the Efficacy, Safety, and Tolerability of Intravitreal Aflibercept Compared to Laser Photocoagulation in Patients With Retinopathy of Prematurity
Acronym
BUTTERFLEYE
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Completed
Study Start Date
October 30, 2019 (Actual)
Primary Completion Date
August 18, 2022 (Actual)
Study Completion Date
August 18, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Regeneron Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Retinopathy of Prematurity

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Masking Description
Open-Label
Allocation
Randomized
Enrollment
127 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Aflibercept Group
Arm Type
Experimental
Arm Description
Patients will receive a single intravitreal (IVT) injection per eligible eye at baseline.
Arm Title
Laser Group
Arm Type
Experimental
Arm Description
Patients will undergo laser treatment in each eligible eye at baseline.
Intervention Type
Drug
Intervention Name(s)
aflibercept
Other Intervention Name(s)
EYLEA®, REGN3, VEGF trap-eye, BAY86-5321
Intervention Description
Administered IVT
Intervention Type
Procedure
Intervention Name(s)
laser photocoagulation
Intervention Description
Transpupillary conventional laser will be administered according to standard local procedures.
Primary Outcome Measure Information:
Title
Percentage of Participants With Absence of Active Retinopathy of Prematurity (ROP) and Unfavorable Structural Outcomes From Baseline to Week 52 of Chronological Age
Description
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.
Time Frame
Baseline to week 52 of chronological age
Secondary Outcome Measure Information:
Title
Percentage of Participants Requiring Intervention With a Second Treatment Modality From Baseline to Week 52 of Chronological Age
Description
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).
Time Frame
Baseline to to week 52 of chronological age
Title
Percentage of Participants With Recurrence of ROP Through Week 52 of Chronological Age
Description
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."
Time Frame
Baseline to week 52 of chronological age
Title
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
Title
Percentage of Participants With Systematic (Non-ocular) TEAEs and TESAEs
Time Frame
Baseline to Week 52 of chronological age

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trial Management
Organizational Affiliation
Regeneron Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Regeneron Study Site
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85016
Country
United States
Facility Name
Regeneron Study Site
City
La Jolla
State/Province
California
ZIP/Postal Code
92093
Country
United States
Facility Name
Regeneron Study Site
City
Loma Linda
State/Province
California
ZIP/Postal Code
92354
Country
United States
Facility Name
Regeneron Study Site
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
Regeneron Study Site
City
Palo Alto
State/Province
California
ZIP/Postal Code
94303
Country
United States
Facility Name
Regeneron Study Site
City
San Diego
State/Province
California
ZIP/Postal Code
92123
Country
United States
Facility Name
Regeneron Study Site
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
Regeneron Study Site
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32608
Country
United States
Facility Name
Regeneron Study Site
City
Augusta
State/Province
Georgia
ZIP/Postal Code
78705
Country
United States
Facility Name
Regeneron Study Site
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Regeneron Study Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02111
Country
United States
Facility Name
Regeneron Study Site
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48105
Country
United States
Facility Name
Regeneron Study Site
City
Royal Oak
State/Province
Michigan
ZIP/Postal Code
48073
Country
United States
Facility Name
Regeneron Study Site
City
Bronx
State/Province
New York
ZIP/Postal Code
10462
Country
United States
Facility Name
Regeneron Study Site
City
Brooklyn
State/Province
New York
ZIP/Postal Code
11203
Country
United States
Facility Name
Regeneron Study Site
City
Brooklyn
State/Province
New York
ZIP/Postal Code
11213
Country
United States
Facility Name
Regeneron Study Site
City
Buffalo
State/Province
New York
ZIP/Postal Code
14209
Country
United States
Facility Name
Regeneron Study Site
City
New York
State/Province
New York
ZIP/Postal Code
10017
Country
United States
Facility Name
Regeneron Study Site
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Regeneron Study Site
City
Valhalla
State/Province
New York
ZIP/Postal Code
10595
Country
United States
Facility Name
Regeneron Study Site
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Regeneron Study Site
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Facility Name
Regeneron Study Site
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02905
Country
United States
Facility Name
Regeneron Study Site
City
Austin
State/Province
Texas
ZIP/Postal Code
78705
Country
United States
Facility Name
Regeneron Study Site
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
Regeneron Study Site
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78240
Country
United States
Facility Name
Regeneron Study Site
City
Morgantown
State/Province
West Virginia
ZIP/Postal Code
26506
Country
United States
Facility Name
Regeneron Study Site
City
Sofia
ZIP/Postal Code
1407
Country
Bulgaria
Facility Name
Regeneron Study Site
City
Sofia
ZIP/Postal Code
1504
Country
Bulgaria
Facility Name
Regeneron Study Site
City
Varna
ZIP/Postal Code
9002
Country
Bulgaria
Facility Name
Regeneron Study Site
City
Medellin
State/Province
Antioquia
ZIP/Postal Code
50034
Country
Colombia
Facility Name
Regeneron Study Site
City
Floridablanca
State/Province
Santander
ZIP/Postal Code
681004
Country
Colombia
Facility Name
Regeneron Study Site
City
Ostrava-Poruba
ZIP/Postal Code
708 52
Country
Czechia
Facility Name
Regeneron Study Site
City
Debrecen
ZIP/Postal Code
H-4032
Country
Hungary
Facility Name
Regeneron Study Site
City
Cheonan
ZIP/Postal Code
31151
Country
Korea, Republic of
Facility Name
Regeneron Study Site
City
Iași
ZIP/Postal Code
700038
Country
Romania
Facility Name
Regeneron Study Site
City
Saint-Petersburg
State/Province
Sankt-Peterburg
ZIP/Postal Code
194100
Country
Russian Federation
Facility Name
Regeneron Study Site
City
Moscow
ZIP/Postal Code
119571
Country
Russian Federation
Facility Name
Regeneron Study Site
City
Moscow
ZIP/Postal Code
119620
Country
Russian Federation
Facility Name
Regeneron Study Site
City
Bratislava
ZIP/Postal Code
833 40
Country
Slovakia
Facility Name
Regeneron Study Site
City
Kaohsiung
ZIP/Postal Code
81346
Country
Taiwan
Facility Name
Regeneron Study Site
City
Pathum Wan
State/Province
Bangkok
ZIP/Postal Code
10330
Country
Thailand
Facility Name
Regeneron Study Site
City
Ratchathewi
State/Province
Bangkok
ZIP/Postal Code
10400
Country
Thailand
Facility Name
Regeneron Study Site
City
Chiangmai
State/Province
Chiang Mai
ZIP/Postal Code
50200
Country
Thailand
Facility Name
Regeneron Study Site
City
Hat Yai
State/Province
Songkhla
ZIP/Postal Code
90110
Country
Thailand
Facility Name
Regeneron Study Site
City
Khon Kaen
ZIP/Postal Code
40002
Country
Thailand
Facility Name
Regeneron Study Site
City
Adana
ZIP/Postal Code
4522
Country
Turkey
Facility Name
Regeneron Study Site
City
Ankara
ZIP/Postal Code
06100
Country
Turkey
Facility Name
Regeneron Study Site
City
Ankara
ZIP/Postal Code
06560
Country
Turkey
Facility Name
Regeneron Study Site
City
Eskisehir
ZIP/Postal Code
26480
Country
Turkey
Facility Name
Regeneron Study Site
City
Ho Chi Minh
ZIP/Postal Code
70000
Country
Vietnam
Facility Name
Regeneron Study Site
City
Hue
ZIP/Postal Code
100000
Country
Vietnam

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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 URL
https://vivli.org/

Learn more about this trial

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

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