Aflibercept for Retinopathy of Prematurity - Intravitreal Injection Versus Laser Therapy

NCT ID: NCT04004208

Last Updated: 2022-05-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 113 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-09-25
• Study Completion Date: 2021-02-12

Brief Summary

The purpose of this study is to demonstrate how well aflibercept works in babies with ROP, comparing it with laser therapy. The study also has the objective to demonstrate how safe aflibercept is when used in babies, and describe how the drug moves into, through and out of the body.

Conditions

Retinopathy of Prematurity (ROP)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Aflibercept arm

Subjects randomized to aflibercept will receive a intravitreal (IVT) injection of Dose A aflibercept per eligible eye at baseline and, if needed, up to a defined number of additional injections in each eye.

Group Type: EXPERIMENTAL

Eylea (Aflibercept, BAY86-5321)

Intervention Type: DRUG

Solution in a sterile glass vial, Dose A, IVT injection.

Laser photocoagulation arm

Subjects randomized to laser photocoagulation will receive treatment in each eligible eye at baseline. Retreatments may be administered if needed.

Group Type: ACTIVE_COMPARATOR

Laser photocoagulation

Intervention Type: PROCEDURE

Transpupillary conventional laser ablative therapy

Interventions

Eylea (Aflibercept, BAY86-5321)

Solution in a sterile glass vial, Dose A, IVT injection.

Intervention Type: DRUG

Laser photocoagulation

Transpupillary conventional laser ablative therapy

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Gestational age at birth ≤ 32 weeks or birth weight ≤ 1500 g
• Subjects with treatment-naïve 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)
• Weight at baseline (day of treatment) ≥ 800 g
• Signed informed consent from parent(s)/legally authorized representative(s), which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

Exclusion Criteria

• Known or suspected chromosomal abnormality, genetic disorder or syndrome
• Previous exposure to any 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 NICU 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 Stages 4 and 5)
• ROP involving only Zone III
• Ocular abnormalities that may interfere with the administration of study intervention or assessment of the study primary endpoint
• Postnatal treatment with oral or intravenous corticosteroids at an equivalent dose of prednisone ≥ 1 mg/kg/day for > 2 weeks within 14 days of the first study intervention
• Previous surgical or nonsurgical treatment for ROP (IVT anti-VEGF injection, ablative laser therapy, cryotherapy, and vitrectomy)
• Participation of the subject or the mother in other clinical trials requiring administration of investigational treatments (other than vitamins and minerals) at the time of screening, or within 30 days or 5 half-lives of administration of the previous study drug, whichever is longer

• Maximum Eligible Age: 32 Weeks
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Regeneron Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

Bayer

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Many Locations

Multiple Locations, , Argentina

Hospital Público Descentralizado "Dr. Guillermo Rawson"

San Juan, , Argentina

Kepler Universitätsklinikum Campus III

Linz, , Austria

Many Locations

Multiple Locations, , Austria

AZ St-Jan Brugge Oostende AV

Bruges, , Belgium

Many Locations

Multiple Locations, , Belgium

Hospital das Clínicas de Botucatu - UNESP Botucatu

Botucatu, São Paulo, Brazil

Many Locations

Multiple Locations, , Brazil

Unifesp/Epm

São Paulo, , Brazil

Many Locations

Multiple Locations, , Bulgaria

UMHAT Sveti Georgi

Plovdiv, , Bulgaria

Acibadem City Clinic Multiprofile Hospital for Active Treatm

Sofia, , Bulgaria

II SOGHAT Sheinovo

Sofia, , Bulgaria

SHOGAT Prof Dimitar Stamatov

Varna, , Bulgaria

Many Locations

Multiple Locations, , Czechia

Fakultni nemocnice Ostrava

Ostrava, , Czechia

Vseobecna fakultni nemocnice v Praze

Prague, , Czechia

P & A KYRIAKOU Children's Hospital

Athens, , Greece

University General Hospital of Ioannina

Ioannina, , Greece

Many Locations

Multiple Locations, , Greece

Papageorgiou General Hospital of Thessaloniki

Thessaloniki, , Greece

Queen Mary Hospital

Hong Kong, , Hong Kong

Many Locations

Multiple Locations, , Hong Kong

EKBC, Uj Szent Janos Korhaz es Szakrendelo

Budapest, , Hungary

Many Locations

Multiple Locations, , Hungary

Many Locations

Multiple Locations, , Israel

Kaplan Medical Center

Rehovot, , Israel

IRCCS Ospedale Pediatrico Bambino Gesù

Rome, Lazio, Italy

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Rome, Lazio, Italy

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, Lombardy, Italy

A.O. di Perugia

Perugia, Umbria, Italy

Many Locations

Multiple Locations, , Italy

University of Occupational and Environmental Health

Kitakyushu, Fukuoka, Japan

Kurume University Hospital

Kurume, Fukuoka, Japan

Okinawa Prefectural Nanbu Medical Center and Children's MC

Shimajiri-gun, Okinawa, Japan

Tokyo Metropolitan Children's Medical Center

Fuchū, Tokyo, Japan

Showa University Hospital

Shinagawa, Tokyo, Japan

Tokyo Metropolitan Bokutoh Hospital

Sumida-ku, Tokyo, Japan

Tokyo Metropolitan Ohtsuka Hospital

Toshima-ku, Tokyo, Japan

Kyushu University Hospital

Fukuoka, , Japan

Fukuoka University Hospital

Fukuoka, , Japan

Fukushima Medical University Hospital

Fukushima, , Japan

Many Locations

Multiple Locations, , Japan

Saitama Children's Medical Center

Saitama, , Japan

Hospital Kuala Lumpur

Kuala Lumpur, , Malaysia

Many Locations

Multiple Locations, , Malaysia

Many Locations

Multiple Locations, , Netherlands

Maxima Medisch Centrum, locatie Veldhoven

Veldhoven, , Netherlands

Many Locations

Multiple Locations, , Poland

Ginekologiczno-Polozniczy SK UM im. K. Marcinkowskiego

Poznan, , Poland

Hospital Prof. Dr. Fernando Fonseca

Amadora, Lisbon District, Portugal

CHLO - Hospital Sao Francisco Xavier

Lisbon, , Portugal

Many Locations

Multiple Locations, , Portugal

Clinical Emergency County Hospital

Cluj-Napoca, Cluj, Romania

Spitalul Clinic de Obstretica si Ginecologie "Cuza Voda"

Iași, , Romania

Many Locations

Multiple Locations, , Romania

FSAI NMRC IRTC "Eye Microsurgery", Kaluga's Branch

Kaluga, , Russia

Russian National Scientific Medical University

Moscow, , Russia

FGBUZ "NPC of special children care n.a. Voino-Yaseneckogo"

Moscow, , Russia

Many Locations

Multiple Locations, , Russia

Pediatric Medical University

Saint Petersburg, , Russia

City Children Hospital ¿1

Saint Petersburg, , Russia

Many Locations

Multiple Locations, , Singapore

KK Women's and Children's Hospital

Singapore, , Singapore

Narodny ustav detskych chorob

Bratislava, , Slovakia

Many Locations

Multiple Locations, , Slovakia

Soon Chun Hyang University Cheonan Hospital

Cheonan-si, Chungcheongnam-do, South Korea

Many Locations

Multiple Locations, , South Korea

Asan Medical Center

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

Hospital Universitario 12 de Octubre

Madrid, , Spain

Hospital Universitario "La Paz"

Madrid, , Spain

Hospital Regional de Málaga

Málaga, , Spain

Many Locations

Multiple Locations, , Spain

Sahlgrenska Universitetssjukhuset

Gothenburg, , Sweden

Many Locations

Multiple Locations, , Sweden

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, , Taiwan

Many Locations

Multiple Locations, , Taiwan

Mackay Memorial Hospital

Taipei, , Taiwan

S.B.U. Adana Sehir Egitim ve Arastirma Hastanesi

Adana, , Turkey (Türkiye)

Hacettepe Universitesi Tip Fakultesi

Ankara, , Turkey (Türkiye)

Baskent Universitesi Tip Fakultesi Hastanesi

Ankara, , Turkey (Türkiye)

Gazi Universitesi Tip Fakultesi

Ankara, , Turkey (Türkiye)

Saglik Bilimleri Universitesi Antalya EA Hastanesi

Antalya, , Turkey (Türkiye)

Eskisehir Osmangazi Universitesi Tip Fakultesi

Eskişehir, , Turkey (Türkiye)

Many Locations

Multiple Locations, , Turkey (Türkiye)

Many Locations

Multiple Locations, , Ukraine

MI"Odesa Regional Children's Clinical Hospital"

Odesa, , Ukraine

Birmingham Womens Hospital

Birmingham, , United Kingdom

Many Locations

Multiple Locations, , United Kingdom

Countries

Argentina; Austria; Belgium; Brazil; Bulgaria; Czechia; Greece; Hong Kong; Hungary; Israel; Italy; Japan; Malaysia; Netherlands; Poland; Portugal; Romania; Russia; Singapore; Slovakia; South Korea; Spain; Sweden; Taiwan; Turkey (Türkiye); Ukraine; United Kingdom

References

Stahl A, Azuma N, Wu WC, Lepore D, Sukgen E, Nakanishi H, Mazela J, Leal S, Pieper A, Schlief S, Eissing T, Turner KC, Zhao A, Winkler J, Hochel J, Kofuncu E, Zimmermann T; FIREFLEYE Study Group. Systemic exposure to aflibercept after intravitreal injection in premature neonates with retinopathy of prematurity: results from the FIREFLEYE randomized phase 3 study. Eye (Lond). 2024 Jun;38(8):1444-1453. doi: 10.1038/s41433-023-02919-9. Epub 2024 Jan 10.

Reference Type: DERIVED

PMID: 38200320 (View on PubMed)

Stahl A, Sukgen EA, Wu WC, Lepore D, Nakanishi H, Mazela J, Moshfeghi DM, Vitti R, Athanikar A, Chu K, Iveli P, Zhao F, Schmelter T, Leal S, Kofuncu E, Azuma N; FIREFLEYE Study Group. Effect of Intravitreal Aflibercept vs Laser Photocoagulation on Treatment Success of Retinopathy of Prematurity: The FIREFLEYE Randomized Clinical Trial. JAMA. 2022 Jul 26;328(4):348-359. doi: 10.1001/jama.2022.10564.

Reference Type: DERIVED

PMID: 35881122 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

http://www.clinicaltrialsregister.eu/

Click here to find information about studies related to Bayer Healthcare products conducted in Europe

http://clinicaltrials.bayer.com/

Click here to find results for studies related to Bayer products

Other Identifiers

2018-002611-99

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

20090

Identifier Type: -

Identifier Source: org_study_id