Retinopathy of Prematurity (ROP)Phase 3FIREFLEYE nextNCT04015180
Extension Study to Evaluate the Long-term Outcomes of Subjects in Study 20090
A Phase 3 study testing Eylea (Aflibercept, BAY86-5321) and Laser photocoagulation in people with Retinopathy of Prematurity (ROP), run by Bayer at 55 sites in 24 countries.
Trial summary
This is a follow-up study to evaluate the long term outcome of babies treated in the FIREFLEYE study. Read more about this study
- Who is it for?
- Ages Up to 13 months
- Conditions the study is for
- Retinopathy of Prematurity (ROP)
- What is being tested?
- Eylea (Aflibercept, BAY86-5321) 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
- 100 participants
- Where
- 55 sitesin 24 countries
- Study dates
- 18 Mar 2020to 19 Sep 2025
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 Up to 13 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Subject was treated in Study 20090
- Age less than 13 months of chronological age
- 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
Who cannot join
- Subject has a condition preventing participation in the study, or performance of study procedures.
Trial locations and contacts
55 sites in 24 countries.
55 sites in 24 countries
Japan10 sites
Tokyo Metropolitan Hospital Organization Tokyo Metropolitan Children's Medical Center
Fuchū, Tokyo, 183-8561
Kyushu University Hospital
Fukuoka, 812-8582
Fukuoka University Hospital
Fukuoka, 814-0180
Fukushima Medical University Hospital
Fukushima, 960-1295
Hospital of the University of Occupational and Environmental Health, Japan
Kitakyushu, Fukuoka, 807-8556
Kurume University Hospital
Kurume, Fukuoka, 830-0011
Kindai University Hospital
Osakasayama-shi, Osaka, 589-8511
Okinawa Prefectural Nanbu Medical Center and Children's MC
Shimajiri-gun, Okinawa, 901-1193
Tokyo Metropolitan Bokutoh Hospital
Sumida-ku, Tokyo, 130-8575
Tokyo Metropolitan Ohtsuka Hospital
Toshima-ku, Tokyo, 170-8476
Turkey (Türkiye)5 sites
Hacettepe Universitesi Tip Fakultesi
Ankara, 6100
Gazi Universitesi Tip Fakultesi
Ankara, 6560
Saglik Bilimleri Universitesi Antalya EA Hastanesi
Antalya, 7100
Eskisehir Osmangazi Universitesi Tip Fakultesi
Eskişehir, 26480
Adana Sehir Egitim ve Arastirma Hastanesi
Yüreğir, 1370
Bulgaria4 sites
UMHAT Sveti Georgi
Plovdiv, 4002
Acibadem City Clinic Multiprofile Hospital for Active Treatm
Sofia, 1407
Spec. Hospital of Ophthalm. for Active Treatment Visus
Sofia, 1619
Spec. Hosp. of Ophthalm. Disease for Active Treatment Varna
Varna, 9000
Italy4 sites
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico - Oculistica
Milan, Lombardy, 20122
A.O. di Perugia_Hospital Santa Maria della Misericordia - S.C. Oculistica
Perugia, Umbria, 06129
Fondazione Policlinico Universitario Agostino Gemelli IRCCS - UOC Oculistica
Rome, Lazio, 00136
Ospedale Pediatrico Bambino Gesù - Oculistica
Rome, Lazio, 00165
Greece3 sites
Children's Hospital of Athens P&A Kyriakou - Pediatric Nephrology Department
Athens, MISSING
General Hospital Of Thessaloniki Papageorgiou-2nd Ophthalmology Clinic
Efkarpia, 564 29
University General Hospital of Ioannina
Ioannina, 45500
Russia3 sites
FSAI NMRC IRTC "Eye Microsurgery", Kaluga's Branch
Kaluga, 248007
FGBUZ "NPC of special children care n.a. Voino-Yaseneckogo"
Moscow, 119620
City Children Hospital ?1
Saint Petersburg, 198205
Spain3 sites
Hospital Universitario 12 de Octubre
Madrid, 28041
Hospital la Paz - oftalmologia
Madrid, 28046
Hospital Universitario Regional De Malaga - Oftalmologia
Málaga, 29011
Brazil2 sites
Hospital das Clínicas de Botucatu - UNESP Botucatu
Botucatu, São Paulo, TBC
Unifesp/Epm
São Paulo, 04024-002
Czechia2 sites
Fakultní nemocnice Ostrava
Ostrava, 708 52
Všeobecná fakultní nemocnice v Praze
Prague, 12808
Portugal2 sites
Hospital Prof. Dr. Fernando Fonseca
Amadora, Lisbon District, 2720-276
Unidade Local De Saúde De Lisboa Ocidental E.P.E.
Lisbon, 1449-005
Romania2 sites
Clinical Emergency County Hospital
Cluj-Napoca, Cluj, 400347
Spitalul Clinic de Obstretica si Ginecologie "Cuza Voda"
Iași, 700038
South Korea2 sites
Soon Chun Hyang University Cheonan Hospital
Cheonan, Chungcheongnam-do, 31151
Asan Medical Center - Oncology Department
Seoul, Seoul Teugbyeolsi, 05505
Taiwan2 sites
Kaohsiung Medical University Chung-Ho Memorial Hospital
Kaohsiung City, Kaohsiung, 807377
Mackay Memorial Hospital
Taipei, 104
Argentina1 site
Hospital Público Descentralizado "Dr. Guillermo Rawson"
San Juan, 5400
Hungary1 site
Eszak-Kozep-budai Centrum, Uj Szent Janos Korhaz és Szakrendelo
Budapest, H-1125
Netherlands1 site
Maxima Medisch Centrum, locatie Veldhoven
Veldhoven, 5504 DB
Ukraine1 site
Institute of Eye Diseases and Tissue Therapy named after V.I. Filatov, Consultative Polyclinic
Odesa, 65061
About this study
Official title: An Extension Study to Evaluate the Long-term Outcomes of Subjects Who Received Treatment for Retinopathy of Prematurity in Study 20090
This is a follow-up study to evaluate the long term outcome of babies treated in the FIREFLEYE study.
- Conditions
- Retinopathy of Prematurity (ROP)
- Being tested
- Eylea (Aflibercept, BAY86-5321), 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.
Eylea (Aflibercept, BAY86-5321)Drug
Treatment administered in 20090. Solution in a sterile glass vial, Dose A, IVT injection.
Laser photocoagulationProcedure or surgery
Treatment administered in 20090. Transpupillary conventional laser ablative therapy
| Study group | Role | What they receive |
|---|---|---|
| Aflibercept arm | Experimental | No study treatment will be administered. The treatments to be evaluated in this study were administered in Study 20090. Receives: Drug: Eylea (Aflibercept, BAY86-5321) |
| Laser photocoagulation arm | Active comparator | No study treatment will be administered. The treatments to be evaluated in this study were administered in Study 20090. Receives: Procedure: Laser photocoagulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Binocular best-corrected visual acuity in Snellen equivalent
Measured: At 5 years of age.
Proportion of subjects with ocular AEs and SAEs
AE: adverse event SAE: serious adverse event
Measured: Up to 5 years of age.
Proportion of subjects with systemic AEs and SAEs
Measured: Up to 5 years of age.
Secondary outcomes (10)
Proportion of subjects developing unfavorable ocular structural outcome
Unfavorable ocular structural outcome include:
retinal detachment, macular dragging, macular fold, retrolental opacity
Measured: At 1,3 and 5 years of age.
Proportion of subjects with absence of active ROP and unfavorable structural outcomes
Measured: At 1 year of age.
Best-corrected visual acuity in each eye
Measured: At 3 and 5 years of age.
Refractive spherical equivalent in each eye
Measured: At 3 and 5 years of age
Neurodevelopmental outcomes using BSID-III
BSID-III: The Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) is a standard series of tests that will assess the development of children in 3 areas: cognition, language, and motor skills. It is recommended to be assessed at screening, 1 year and 2 years of age. The assessment at 2 years of age is mandatory.
Measured: At 2 years of age
Neurodevelopmental outcomes using WPPSI-IV
WPPSI-IV: The Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition is designed to assess development of older children and is recommended to be performed at 3, 4 and 5 years of age. The assessment at 5 years of age is mandatory. In cases where the WPSSI-IV cannot be used, the Differential Ability Scales II (DAS-II) may be used as an alternative.
Measured: At 5 years of age
Neurodevelopmental outcomes using VABS-II
VABS-II: Vineland Adaptive Behavior Scales, Second Edition Expanded Interview will be included, which includes 4 areas: Communication, Daily Living skills, Socialization and Motor Skills. It is recommended to be assessed at 2, 3, 4 and 5 years of age. The assessments at 2 years and 5 years of age are mandatory.
Measured: At 2 and 5 years of age
Proportion of subjects with recurrence of ROP
Measured: At 3 and 5 years of age.
Proportion of subjects requiring treatment for ROP
Measured: Up to 5 years of age.
Proportion of subjects requiring ophthalmological treatment
Measured: Up to 5 years of age.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jul 2019
- Study start18 Mar 2020
- Primary completion19 Sep 2025
- Study completion19 Sep 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Retinopathy of Prematurity (ROP)Studies of the same condition, open and under way.
- More trials run by BayerThe 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
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bayer
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Regeneron Pharmaceuticals
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04015180
- Sponsor's protocol ID
- 20275
- Other IDs
- 2023-504207-89-00, 2018-003180-54, 2018, 2023
- Acronym
- FIREFLEYE next
- Status last verified
- Oct 2025
- First submitted
- 28 Jun 2019
- Last updated
- 10 Oct 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014. Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.
Publications
Stahl A, Nakanishi H, Lepore D, Wu WC, Azuma N, Jacas C, Vitti R, Athanikar A, Chu K, Iveli P, Zhao F, Leal S, Schlief S, Schmelter T, Miller T, Kofuncu E, Fielder A; FIREFLEYE next Study Group. Intravitreal Aflibercept vs Laser Therapy for Retinopathy of Prematurity: Two-Year Efficacy and Safety Outcomes in the Nonrandomized Controlled Trial FIREFLEYE next. JAMA Netw Open. 2024 Apr 1;7(4):e248383. doi: 10.1001/jamanetworkopen.2024.8383.
PubMed 38687481
Study at a glance
From the registry record, last updated by the sponsor on 10 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Extension Study to Evaluate the Long-term Outcomes of Subjects Who Received Treatment for Retinopathy of Prematurity in Study 20090
- ClinicalTrials.gov ID
- NCT04015180
- Acronym / sponsor ID
- FIREFLEYE next / 20275
- Conditions
- Retinopathy of Prematurity (ROP)
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- BayerIndustry (pharma, biotech, devices)
- Collaborators
- Regeneron Pharmaceuticals
- Study start
- 18 Mar 2020 (actual)
- Primary completion
- 19 Sep 2025 (actual)
- Study completion
- 19 Sep 2025 (actual)
- First posted
- 10 Jul 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a follow-up study to evaluate the long term outcome of babies treated in the FIREFLEYE study.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Aflibercept arm | Experimental | Drug: Eylea (Aflibercept, BAY86-5321)No study treatment will be administered. The treatments to be evaluated in this study were administered in Study 20090. |
| Laser photocoagulation arm | Active comparator | Procedure: Laser photocoagulationNo study treatment will be administered. The treatments to be evaluated in this study were administered in Study 20090. |
Who may qualify
- Ages
- Up to 13 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- Subject was treated in Study 20090
- Age less than 13 months of chronological age
- 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
Key exclusion criteria (1 listed)
- Subject has a condition preventing participation in the study, or performance of study procedures.
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 |
|---|---|---|
| Eylea (Aflibercept, BAY86-5321)Treatment administered in 20090. Solution in a sterile glass vial, Dose A, IVT injection. | Drug | Aflibercept arm |
| Laser photocoagulationTreatment administered in 20090. Transpupillary conventional laser ablative therapy | Procedure or surgery | Laser photocoagulation arm |
Primary outcome
Binocular best-corrected visual acuity in Snellen equivalent
Time frame: At 5 years of age.
Proportion of subjects with ocular AEs and SAEs
Time frame: Up to 5 years of age.
AE: adverse event SAE: serious adverse event
Proportion of subjects with systemic AEs and SAEs
Time frame: Up to 5 years of age.
10 secondary outcomes
Proportion of subjects developing unfavorable ocular structural outcome
Time frame: At 1,3 and 5 years of age.
Proportion of subjects with absence of active ROP and unfavorable structural outcomes
Time frame: At 1 year of age.
Best-corrected visual acuity in each eye
Time frame: At 3 and 5 years of age.
Refractive spherical equivalent in each eye
Time frame: At 3 and 5 years of age
Neurodevelopmental outcomes using BSID-III
Time frame: At 2 years of age
Neurodevelopmental outcomes using WPPSI-IV
Time frame: At 5 years of age
Neurodevelopmental outcomes using VABS-II
Time frame: At 2 and 5 years of age
Proportion of subjects with recurrence of ROP
Time frame: At 3 and 5 years of age.
Proportion of subjects requiring treatment for ROP
Time frame: Up to 5 years of age.
Proportion of subjects requiring ophthalmological treatment
Time frame: Up to 5 years of age.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Oct 2025.
- Derived from this study: PubMed 38687481Stahl A, Nakanishi H, Lepore D, Wu WC, Azuma N, Jacas C, Vitti R, Athanikar A, Chu K, Iveli P, Zhao F, Leal S, Schlief S, Schmelter T, Miller T, Kofuncu E, Fielder A; FIREFLEYE next Study Group. Intravitreal Aflibercept vs Laser Therapy for Retinopathy of Prematurity: Two-Year Efficacy and Safety Outcomes in the Nonrandomized Controlled Trial FIREFLEYE next. JAMA Netw Open. 2024 Apr 1;7(4):e248383. doi: 10.1001/jamanetworkopen.2024.8383.
- Individual participant dataSharing planned: No. Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014. Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.
Related trials for Retinopathy of Prematurity (ROP)
RecruitingObservational study
An Observational Study to Collect Data on How Aflibercept (Eylea) Given Using a Paediatric Dosing Device is Used in Preterm Babies With Retinopathy of Prematurity in the United Kingdom (UK)
Retinopathy of Prematurity, Preterm Infants
RecruitingObservational study
The Correlation Between Red Cell Transfusion and Complications of Prematurity
Retinopathy of Prematurity (ROP), Bronchopulmonary Dysplasia (BPD)
RecruitingObservational study
Imaging Retinal Vasculature in Infant Eyes
Retinopathy of Prematurity
RecruitingPhase 1
Safety, PK and PD of FLQ-101 in Premature Neonates
Retinopathy of Prematurity (ROP)
Recruiting
Analyzing Retinal Microanatomy in Retinopathy of Prematurity to Improve Care
Retinopathy of Prematurity (ROP)
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.
The record lists no contact. Use the official record to reach the sponsor.
55 sites in 24 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Eylea (Aflibercept, BAY86-5321) and Laser photocoagulation in people with Retinopathy of Prematurity (ROP), run by Bayer at 55 sites in 24 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 3 inclusion and 1 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 10 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 55 sites in Japan, Turkey (Türkiye), Bulgaria, Italy, Greece and 19 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Binocular best-corrected visual acuity in Snellen equivalent (time frame: At 5 years of age.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04015180, which also lists 1 linked publication.
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 10 Oct 2025.