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

Retinopathy of Prematurity Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04101721
• Other study ID #: VGFTe-ROP-1920
• Secondary ID: 2019-001764-29
• Status: Completed
• Phase: Phase 3
• Start date: October 30, 2019
• Est. completion date: August 18, 2022

Study information

• Verified date: July 2023
• Source: Regeneron Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 and tolerability of aflibercept.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 127
• Est. completion date: August 18, 2022
• Est. primary completion date: August 18, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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.

Related Conditions & MeSH terms

• Premature Birth
• Retinal Diseases
• Retinopathy of Prematurity

Intervention

Drug:
• aflibercept
Administered IVT

Procedure:
• laser photocoagulation
Transpupillary conventional laser will be administered according to standard local procedures.

Locations

Country	Name	City	State
Bulgaria	Regeneron Study Site	Sofia
Bulgaria	Regeneron Study Site	Sofia
Bulgaria	Regeneron Study Site	Varna
Colombia	Regeneron Study Site	Floridablanca	Santander
Colombia	Regeneron Study Site	Medellin	Antioquia
Czechia	Regeneron Study Site	Ostrava-Poruba
Hungary	Regeneron Study Site	Debrecen
Korea, Republic of	Regeneron Study Site	Cheonan
Romania	Regeneron Study Site	Ia?i
Russian Federation	Regeneron Study Site	Moscow
Russian Federation	Regeneron Study Site	Moscow
Russian Federation	Regeneron Study Site	Saint-Petersburg	Sankt-Peterburg
Slovakia	Regeneron Study Site	Bratislava
Taiwan	Regeneron Study Site	Kaohsiung
Thailand	Regeneron Study Site	Chiangmai	Chiang Mai
Thailand	Regeneron Study Site	Hat Yai	Songkhla
Thailand	Regeneron Study Site	Khon Kaen
Thailand	Regeneron Study Site	Pathum Wan	Bangkok
Thailand	Regeneron Study Site	Ratchathewi	Bangkok
Turkey	Regeneron Study Site	Adana
Turkey	Regeneron Study Site	Ankara
Turkey	Regeneron Study Site	Ankara
Turkey	Regeneron Study Site	Eskisehir
United States	Regeneron Study Site	Ann Arbor	Michigan
United States	Regeneron Study Site	Augusta	Georgia
United States	Regeneron Study Site	Austin	Texas
United States	Regeneron Study Site	Boston	Massachusetts
United States	Regeneron Study Site	Bronx	New York
United States	Regeneron Study Site	Brooklyn	New York
United States	Regeneron Study Site	Brooklyn	New York
United States	Regeneron Study Site	Buffalo	New York
United States	Regeneron Study Site	Chicago	Illinois
United States	Regeneron Study Site	Cleveland	Ohio
United States	Regeneron Study Site	Gainesville	Florida
United States	Regeneron Study Site	La Jolla	California
United States	Regeneron Study Site	Loma Linda	California
United States	Regeneron Study Site	Morgantown	West Virginia
United States	Regeneron Study Site	New York	New York
United States	Regeneron Study Site	New York	New York
United States	Regeneron Study Site	Oklahoma City	Oklahoma
United States	Regeneron Study Site	Orange	California
United States	Regeneron Study Site	Palo Alto	California
United States	Regeneron Study Site	Phoenix	Arizona
United States	Regeneron Study Site	Providence	Rhode Island
United States	Regeneron Study Site	Royal Oak	Michigan
United States	Regeneron Study Site	San Antonio	Texas
United States	Regeneron Study Site	San Antonio	Texas
United States	Regeneron Study Site	San Diego	California
United States	Regeneron Study Site	San Francisco	California
United States	Regeneron Study Site	Valhalla	New York
Vietnam	Regeneron Study Site	Ho Chi Minh
Vietnam	Regeneron Study Site	Hue

Sponsors (1)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals

Countries where clinical trial is conducted

United States,  Vietnam,  Bulgaria,  Colombia,  Czechia,  Hungary,  Korea, Republic of,  Romania,  Russian Federation,  Slovakia,  Taiwan,  Thailand,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline to week 52 of chronological age
Secondary	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).	Baseline to to week 52 of chronological age
Secondary	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."	Baseline to week 52 of chronological age
Secondary	Percentage of Participants With Ocular Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)		Baseline to Week 52 of chronological age
Secondary	Percentage of Participants With Systematic (Non-ocular) TEAEs and TESAEs		Baseline to Week 52 of chronological age