Retinopathy of PrematurityPhase 3BUTTERFLEYENCT04101721
Study to Assess the Efficacy, Safety, and Tolerability of Intravitreal Aflibercept Compared to Laser Photocoagulation in Patients With Retinopathy of Prematurity
A Phase 3 study testing aflibercept and laser photocoagulation in people with Retinopathy of Prematurity, run by Regeneron Pharmaceuticals at 52 sites in 13 countries.
Trial 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… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Retinopathy of Prematurity
- What is being tested?
- aflibercept and laser photocoagulation
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 127 participants
- Where
- 52 sitesin 13 countries
- Study dates
- 30 Oct 2019to 18 Aug 2022
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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.
Trial locations and contacts
52 sites in 13 countries.
52 sites in 13 countries
United States27 sites
Regeneron Study Site
Ann Arbor, Michigan, 48105
Regeneron Study Site
Augusta, Georgia, 78705
Regeneron Study Site
Austin, Texas, 78705
Regeneron Study Site
Boston, Massachusetts, 02111
Regeneron Study Site
Brooklyn, New York, 11203
Regeneron Study Site
Brooklyn, New York, 11213
Regeneron Study Site
Buffalo, New York, 14209
Regeneron Study Site
Chicago, Illinois, 60612
Regeneron Study Site
Cleveland, Ohio, 44106
Regeneron Study Site
Gainesville, Florida, 32608
Regeneron Study Site
La Jolla, California, 92093
Regeneron Study Site
Loma Linda, California, 92354
Regeneron Study Site
Morgantown, West Virginia, 26506
Regeneron Study Site
New York, New York, 10017
Regeneron Study Site
New York, New York, 10029
Regeneron Study Site
Oklahoma City, Oklahoma, 73104
Regeneron Study Site
Orange, California, 92868
Regeneron Study Site
Palo Alto, California, 94303
Regeneron Study Site
Phoenix, Arizona, 85016
Regeneron Study Site
Providence, Rhode Island, 02905
Regeneron Study Site
Royal Oak, Michigan, 48073
Regeneron Study Site
San Antonio, Texas, 78229
Regeneron Study Site
San Antonio, Texas, 78240
Regeneron Study Site
San Diego, California, 92123
Regeneron Study Site
San Francisco, California, 94143
Regeneron Study Site
The Bronx, New York, 10462
Regeneron Study Site
Valhalla, New York, 10595
Thailand5 sites
Regeneron Study Site
Chiang Mai, Chiang Mai, 50200
Regeneron Study Site
Hat Yai, Changwat Songkhla, 90110
Regeneron Study Site
Khon Kaen, 40002
Regeneron Study Site
Pathum Wan, Bangkok, 10330
Regeneron Study Site
Ratchathewi, Bangkok, 10400
Turkey (Türkiye)4 sites
Regeneron Study Site
Adana, 4522
Regeneron Study Site
Ankara, 06100
Regeneron Study Site
Ankara, 06560
Regeneron Study Site
Eskişehir, 26480
Bulgaria3 sites
Regeneron Study Site
Sofia, 1407
Regeneron Study Site
Sofia, 1504
Regeneron Study Site
Varna, 9002
Russia3 sites
Regeneron Study Site
Moscow, 119571
Regeneron Study Site
Moscow, 119620
Regeneron Study Site
Saint Petersburg, Sankt-Peterburg, 194100
Colombia2 sites
Regeneron Study Site
Floridablanca, Santander Department, 681004
Regeneron Study Site
Medellín, Antioquia, 50034
Vietnam2 sites
Regeneron Study Site
Ho Chi Minh City, 70000
Regeneron Study Site
Huế, 100000
About this study
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
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.
- Conditions
- Retinopathy of Prematurity
- Being tested
- aflibercept, laser photocoagulation
- Medical subject headings
- Retinopathy of Prematurity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
afliberceptDrug
Also called EYLEA®, REGN3, VEGF trap-eye, BAY86-5321
Administered IVT
laser photocoagulationProcedure or surgery
Transpupillary conventional laser will be administered according to standard local procedures.
| Study group | Role | What they receive |
|---|---|---|
| Aflibercept Group | Experimental | Patients will receive a single intravitreal (IVT) injection per eligible eye at baseline. Receives: Drug: aflibercept |
| Laser Group | Experimental | Patients will undergo laser treatment in each eligible eye at baseline. Receives: Procedure: laser photocoagulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline to week 52 of chronological age
Secondary outcomes (4)
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).
Measured: Baseline to to week 52 of chronological age
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."
Measured: Baseline to week 52 of chronological age
Percentage of Participants With Ocular Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
Measured: Baseline to Week 52 of chronological age
Percentage of Participants With Systematic (Non-ocular) TEAEs and TESAEs
Measured: Baseline to Week 52 of chronological age
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Sep 2019
- Study start30 Oct 2019
- Primary completion18 Aug 2022
- Study completion18 Aug 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Retinopathy of PrematurityStudies of the same condition, open and under way.
- More trials run by Regeneron PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 127 participants (actual)
Sponsor and investigators
- Lead sponsor
- Regeneron Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trial Management, Study director, Regeneron Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04101721
- Sponsor's protocol ID
- VGFTe-ROP-1920
- Other IDs
- 2019-001764-29, 2019
- Acronym
- BUTTERFLEYE
- Status last verified
- Jul 2023
- First submitted
- 23 Sep 2019
- Last updated
- 20 Jul 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
Study at a glance
From the registry record, last updated by the sponsor on 20 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04101721
- Acronym / sponsor ID
- BUTTERFLEYE / VGFTe-ROP-1920
- Conditions
- Retinopathy of Prematurity
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 127 participants (actual)
- Lead sponsor
- Regeneron PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 30 Oct 2019 (actual)
- Primary completion
- 18 Aug 2022 (actual)
- Study completion
- 18 Aug 2022 (actual)
- First posted
- 24 Sep 2019 (actual)
- Results
- Posted 20 Jul 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Aflibercept Group | Experimental | Drug: afliberceptPatients will receive a single intravitreal (IVT) injection per eligible eye at baseline. |
| Laser Group | Experimental | Procedure: laser photocoagulationPatients will undergo laser treatment in each eligible eye at baseline. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- 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:
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| afliberceptAlso: EYLEA®, REGN3, VEGF trap-eye, BAY86-5321Administered IVT | Drug | Aflibercept Group |
| laser photocoagulationTranspupillary conventional laser will be administered according to standard local procedures. | Procedure or surgery | Laser Group |
Primary outcome
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.
4 secondary outcomes
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
Percentage of Participants With Recurrence of ROP Through Week 52 of Chronological Age
Time frame: 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
Percentage of Participants With Systematic (Non-ocular) TEAEs and TESAEs
Time frame: Baseline to Week 52 of chronological age
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jul 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trial Management study director
Regeneron Pharmaceuticals
52 sites in 13 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing aflibercept and laser photocoagulation in people with Retinopathy of Prematurity, run by Regeneron Pharmaceuticals at 52 sites in 13 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 52 sites in United States, Thailand, Turkey (Türkiye), Bulgaria, Russia and 8 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Jul 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jul 2023.