Aflibercept for Retinopathy of Prematurity - Intravitreal Injection Versus Laser Therapy

NCT04004208 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: 200902018-002611-99
• Study Type: interventional
• Target: 113
• Locations: 27 countries
• Sites: 90

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)

Outcome Measures

Primary Outcomes (1)

• Proportion of Participants With Absence of Active ROP and Unfavorable Structural Outcomes

  Active ROP was defined as ROP requiring treatment. Unfavorable structural outcomes included retinal detachment, macular dragging, macular fold, or retrolental opacity.

  At 24 weeks after starting study treatment

Secondary Outcomes (12)

• Proportion of Participants Requiring Intervention With a Second Treatment Modality

  From baseline (treatment) up to week 24.

• Proportion of Participants With Recurrence of ROP

  From baseline (treatment) up to week 24.

• Exploration of ROP Activity Scale Proposed by the International Neonatal Consortium

  From baseline (treatment) up to week 24.

• Percentage of Participants With Ocular Treatment-emergent Adverse Events (TEAEs)

  From baseline (treatment) up to week 24

• Percentage of Participants With Ocular Serious Adverse Events (SAEs)

  From baseline (treatment) up to week 24

Study Arms (2)

Aflibercept arm

EXPERIMENTAL

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.

Drug: Eylea (Aflibercept, BAY86-5321)

Laser photocoagulation arm

ACTIVE COMPARATOR

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

Procedure: Laser photocoagulation

Interventions

Eylea (Aflibercept, BAY86-5321) DRUG

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

Aflibercept arm

Laser photocoagulation PROCEDURE

Transpupillary conventional laser ablative therapy

Laser photocoagulation arm

Eligibility Criteria

• Age: Up to 32 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Bayer: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (90)

Many Locations

Multiple Locations, Argentina

Location

Hospital Público Descentralizado "Dr. Guillermo Rawson"

San Juan, 5400, Argentina

Location

Kepler Universitätsklinikum Campus III

Linz, 4021, Austria

Location

Many Locations

Multiple Locations, Austria

Location

AZ St-Jan Brugge Oostende AV

Bruges, 8000, Belgium

Location

Many Locations

Multiple Locations, Belgium

Location

Hospital das Clínicas de Botucatu - UNESP Botucatu

Botucatu, São Paulo, 18618 970, Brazil

Location

Many Locations

Multiple Locations, Brazil

Location

Unifesp/Epm

São Paulo, 04023-061, Brazil

Location

Many Locations

Multiple Locations, Bulgaria

Location

UMHAT Sveti Georgi

Plovdiv, 4002, Bulgaria

Location

Acibadem City Clinic Multiprofile Hospital for Active Treatm

Sofia, 1407, Bulgaria

Location

II SOGHAT Sheinovo

Sofia, 1504, Bulgaria

Location

SHOGAT Prof Dimitar Stamatov

Varna, 9000, Bulgaria

Location

Many Locations

Multiple Locations, Czechia

Location

Fakultni nemocnice Ostrava

Ostrava, 708 52, Czechia

Location

Vseobecna fakultni nemocnice v Praze

Prague, 12808, Czechia

Location

P & A KYRIAKOU Children's Hospital

Athens, 11527, Greece

Location

University General Hospital of Ioannina

Ioannina, 45500, Greece

Location

Many Locations

Multiple Locations, Greece

Location

Papageorgiou General Hospital of Thessaloniki

Thessaloniki, 56403, Greece

Location

Queen Mary Hospital

Hong Kong, Hong Kong

Location

Many Locations

Multiple Locations, Hong Kong

Location

EKBC, Uj Szent Janos Korhaz es Szakrendelo

Budapest, 1125, Hungary

Location

Many Locations

Multiple Locations, Hungary

Location

Many Locations

Multiple Locations, Israel

Location

Kaplan Medical Center

Rehovot, 7661041, Israel

Location

IRCCS Ospedale Pediatrico Bambino Gesù

Rome, Lazio, 00165, Italy

Location

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Rome, Lazio, 00168, Italy

Location

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, Lombardy, 20122, Italy

Location

A.O. di Perugia

Perugia, Umbria, 06129, Italy

Location

Many Locations

Multiple Locations, Italy

Location

University of Occupational and Environmental Health

Kitakyushu, Fukuoka, 807-8556, Japan

Location

Kurume University Hospital

Kurume, Fukuoka, 830-0011, Japan

Location

Okinawa Prefectural Nanbu Medical Center and Children's MC

Shimajiri-gun, Okinawa, 901-1193, Japan

Location

Tokyo Metropolitan Children's Medical Center

Fuchū, Tokyo, 183-8561, Japan

Location

Showa University Hospital

Shinagawa, Tokyo, 142-8666, Japan

Location

Tokyo Metropolitan Bokutoh Hospital

Sumida-ku, Tokyo, 130-8575, Japan

Location

Tokyo Metropolitan Ohtsuka Hospital

Toshima-ku, Tokyo, 170-8476, Japan

Location

Kyushu University Hospital

Fukuoka, 812-8582, Japan

Location

Fukuoka University Hospital

Fukuoka, 814-0180, Japan

Location

Fukushima Medical University Hospital

Fukushima, 960-1295, Japan

Location

Many Locations

Multiple Locations, Japan

Location

Saitama Children's Medical Center

Saitama, 330-8777, Japan

Location

Hospital Kuala Lumpur

Kuala Lumpur, 50586, Malaysia

Location

Many Locations

Multiple Locations, Malaysia

Location

Many Locations

Multiple Locations, Netherlands

Location

Maxima Medisch Centrum, locatie Veldhoven

Veldhoven, 5504 DB, Netherlands

Location

Many Locations

Multiple Locations, Poland

Location

Ginekologiczno-Polozniczy SK UM im. K. Marcinkowskiego

Poznan, 60-535, Poland

Location

Hospital Prof. Dr. Fernando Fonseca

Amadora, Lisbon District, 2720-276, Portugal

Location

CHLO - Hospital Sao Francisco Xavier

Lisbon, 1449-005, Portugal

Location

Many Locations

Multiple Locations, Portugal

Location

Clinical Emergency County Hospital

Cluj-Napoca, Cluj, 400006, Romania

Location

Spitalul Clinic de Obstretica si Ginecologie "Cuza Voda"

Iași, 700038, Romania

Location

Many Locations

Multiple Locations, Romania

Location

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

Kaluga, 248007, Russia

Location

Russian National Scientific Medical University

Moscow, 117997, Russia

Location

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

Moscow, 119620, Russia

Location

Many Locations

Multiple Locations, Russia

Location

Pediatric Medical University

Saint Petersburg, 194100, Russia

Location

City Children Hospital ¿1

Saint Petersburg, 198205, Russia

Location

Many Locations

Multiple Locations, Singapore

Location

KK Women's and Children's Hospital

Singapore, 229899, Singapore

Location

Narodny ustav detskych chorob

Bratislava, 833 41, Slovakia

Location

Many Locations

Multiple Locations, Slovakia

Location

Soon Chun Hyang University Cheonan Hospital

Cheonan-si, Chungcheongnam-do, South Korea

Location

Many Locations

Multiple Locations, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario "La Paz"

Madrid, 28046, Spain

Location

Hospital Regional de Málaga

Málaga, 29011, Spain

Location

Many Locations

Multiple Locations, Spain

Location

Sahlgrenska Universitetssjukhuset

Gothenburg, Sweden

Location

Many Locations

Multiple Locations, Sweden

Location

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, 80756, Taiwan

Location

Many Locations

Multiple Locations, Taiwan

Location

Mackay Memorial Hospital

Taipei, 10449, Taiwan

Location

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

Adana, 4522, Turkey (Türkiye)

Location

Hacettepe Universitesi Tip Fakultesi

Ankara, 06100, Turkey (Türkiye)

Location

Baskent Universitesi Tip Fakultesi Hastanesi

Ankara, 06490, Turkey (Türkiye)

Location

Gazi Universitesi Tip Fakultesi

Ankara, 06500, Turkey (Türkiye)

Location

Saglik Bilimleri Universitesi Antalya EA Hastanesi

Antalya, 07100, Turkey (Türkiye)

Location

Eskisehir Osmangazi Universitesi Tip Fakultesi

Eskişehir, 26480, Turkey (Türkiye)

Location

Many Locations

Multiple Locations, Turkey (Türkiye)

Location

Many Locations

Multiple Locations, Ukraine

Location

MI"Odesa Regional Children's Clinical Hospital"

Odesa, 65031, Ukraine

Location

Birmingham Womens Hospital

Birmingham, B15 2TG, United Kingdom

Location

Many Locations

Multiple Locations, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 38200320 DERIVED

• 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.

  PMID: 35881122 DERIVED

Related Links

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

MeSH Terms

Conditions

Retinopathy of Prematurity

Interventions

aflibercept

Condition Hierarchy (Ancestors)

Retinal Diseases; Eye Diseases; Infant, Premature, Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Therapeutic Area Head
• Organization: Bayer

clinical-trials-contact@bayer.com

(+) 1-888-8422937

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 28, 2019
• First Posted: July 1, 2019
• Study Start: September 25, 2019
• Primary Completion: February 12, 2021
• Study Completion: February 12, 2021
• Last Updated: May 6, 2022
• Results First Posted: May 6, 2022

Record last verified: 2022-05

Locations

PL (2); RO (3); TU (7); UA (2); SL (2); JP (12); BU (5); RU (6); AR (2); HK (2); MY (2); IT (5); BE (2); ES (4); KR (4); GB (2); BR (3); AU (2); GR (4); HU (2); CZ (3); PT (3); SG (2); IL (2); SE (2); TW (3); NL (2)