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

• ClinicalTrials.gov Identifier: NCT04101721
• Recruitment Status: Recruiting
• First Posted: September 24, 2019
• Last Update Posted: January 7, 2020
• Sponsor: Regeneron Pharmaceuticals
• Information provided by (Responsible Party): Regeneron Pharmaceuticals

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.

Condition or disease	Intervention/treatment	Phase
Retinopathy of Prematurity	Drug: aflibercept; Procedure: laser photocoagulation	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 112 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Masking Description: Open-Label
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: October 30, 2019
• Estimated Primary Completion Date: April 1, 2022
• Estimated Study Completion Date: April 1, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Proportion of patients with absence of active retinopathy of prematurity (ROP) and of unfavorable structural outcomes [ Time Frame: At Week 52 of chronological age ]
   For patients with both eyes enrolled in the study, both eyes must meet the endpoint.

Secondary Outcome Measures :

1. Proportion of patients requiring intervention with a second treatment modality [ Time Frame: Baseline to Week 52 of chronological age ]
2. Proportion of patients with recurrence of ROP [ Time Frame: Through Week 52 of chronological age ]
3. Proportion of patients with ocular treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) [ Time Frame: Baseline to Week 52 of chronological age ]
4. Proportion of patients with systematic TEAEs and SAEs [ Time Frame: Baseline to Week 52 of chronological age ]

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Contacts

Contact: Clinical Trials Administrator; 844-734-6643; clinicaltrials@regeneron.com

Locations

United States, Colorado

Regeneron Study Site; Not yet recruiting

Aurora, Colorado, United States, 80045

United States, New York

Regeneron Study Site; Not yet recruiting

Jamaica, New York, United States, 11418

United States, West Virginia

Regeneron Study Site; Recruiting

Morgantown, West Virginia, United States, 26506

Colombia

Regeneron Study Site; Not yet recruiting

Medellin, Antioquia, Colombia, 050034

Regeneron Study Site; Not yet recruiting

Floridablanca, Santander, Colombia, 681004

Thailand

Regeneron Study Site; Not yet recruiting

Chiangmai, Chiang Mai, Thailand, 50200

Regeneron Study Site; Not yet recruiting

Hat Yai, Songkhla, Thailand, 90110

Regeneron Study Site; Not yet recruiting

Bangkok, Thailand, 10330

Regeneron Study Site; Not yet recruiting

Bangkok, Thailand, 10400

Sponsors and Collaborators

Regeneron Pharmaceuticals

Investigators

• Study Director: Clinical Trial Management; Regeneron Pharmaceuticals

More Information

• Responsible Party: Regeneron Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT04101721
• Other Study ID Numbers: VGFTe-ROP-1920
• First Posted: September 24, 2019
• Last Update Posted: January 7, 2020
• Last Verified: November 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code
• 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.
• 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).
• URL: https://errs.regeneron.com/external

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Retinal Diseases; Retinopathy of Prematurity; Premature Birth; Eye Diseases; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Infant, Premature, Diseases; Infant, Newborn, Diseases