Trial Condition(s):
Retinopathy of prematurity (ROP)
Aflibercept for retinopathy of prematurity – intravitreal injection versus laser therapy (FIREFLEYE)
Bayer Identifier:
20090
ClinicalTrials.gov Identifier:
EudraCT Number:
EU CT Number:
Not Available
Trial Purpose
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.
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
Trial Summary
Enrollment Goal
Trial Dates
Phase
Could I receive a placebo?
Products
Accepts Healthy Volunteers
Where to Participate
| Locations | Status | |
|---|---|---|
Locations Hacettepe Universitesi Tip Fakultesi Ankara, Turkey, 06100 | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Baskent Universitesi Tip Fakultesi Hastanesi Ankara, Turkey, 06490 | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Eskisehir Osmangazi Universitesi Tip Fakultesi Eskisehir, Turkey, 26480 | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Saglik Bilimleri Universitesi Antalya EA Hastanesi Antalya, Turkey, 07100 | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Fondazione Policlinico Universitario Agostino Gemelli IRCCS Roma, Italy, 00168 | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations IRCCS Ospedale Pediatrico Bambino Gesù Roma, Italy, 00165 | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations A.O. di Perugia Perugia, Italy, 06129 | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano, Italy, 20122 | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations S.B.U. Adana Sehir Egitim ve Arastirma Hastanesi Adana, Turkey, 4522 | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Gazi Universitesi Tip Fakultesi Ankara, Turkey, 06500 | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Hospital Regional de Málaga Málaga, Spain, 29011 | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Kepler Universitätsklinikum Campus III Linz, Austria, 4021 | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Samsung Medical Center Seoul, South Korea, 06351 | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Asan Medical Center Seoul, South Korea, 05505 | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Soon Chun Hyang University Cheonan Hospital Cheonan-si, South Korea | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Queen Mary Hospital Hong Kong, Hong Kong, China | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Kaplan Medical Center Rehovot, Israel, 7661041 | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Acibadem City Clinic Multiprofile Hospital for Active Treatm Sofia, Bulgaria, 1407 | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations UMHAT Sveti Georgi Plovdiv, Bulgaria, 4002 | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations II SOGHAT Sheinovo Sofia, Bulgaria, 1504 | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations SHOGAT Prof Dimitar Stamatov Varna, Bulgaria, 9000 | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Hospital Prof. Dr. Fernando Fonseca Amadora, Portugal, 2720-276 | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations CHLO - Hospital Sao Francisco Xavier Lisboa, Portugal, 1449-005 | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Hospital Universitario "La Paz" Madrid, Spain, 28046 | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Hospital Universitario 12 de Octubre Madrid, Spain, 28041 | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations AZ St-Jan Brugge Oostende AV BRUGGE, Belgium, 8000 | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Vseobecna fakultni nemocnice v Praze Praha 2, Czech Republic, 12808 | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Fakultni nemocnice Ostrava Ostrava, Czech Republic, 708 52 | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations EKBC, Uj Szent Janos Korhaz es Szakrendelo Budapest, Hungary, 1125 | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations UNIFESP/EPM Sao Paulo, Brazil, 04023-061 | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations FGBUZ "NPC of special children care n.a. Voino-Yaseneckogo" Moscow, Russia, 119620 | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations FSAI NMRC IRTC "Eye Microsurgery", Kaluga’s Branch Kaluga, Russia, 248007 | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Pediatric Medical University Saint-Petersburg, Russia, 194100 | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations City Children Hospital ¿1 Saint-Petersburg, Russia, 198205 | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Narodny ustav detskych chorob Bratislava, Slovakia, 833 41 | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations MI"Odesa Regional Children's Clinical Hospital" Odesa, Ukraine, 65031 | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Kaohsiung Medical University Chung-Ho Memorial Hospital Kaohsiung, Taiwan, China, 80756 | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Mackay Memorial Hospital Taipei, Taiwan, China, 10449 | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Ginekologiczno-Polozniczy SK UM im. K. Marcinkowskiego Poznan, Poland, 60-535 | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Hospital Público Descentralizado "Dr. Guillermo Rawson" San Juan, Argentina, 5400 | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Russian National Scientific Medical University Moscow, Russia, 117997 | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Sahlgrenska Universitetssjukhuset Göteborg, Sweden | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations P & A KYRIAKOU Children's Hospital Athens, Greece, 11527 | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations University General Hospital of Ioannina Ioannina, Greece, 45500 | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Papageorgiou General Hospital of Thessaloniki Thessaloniki, Greece, 56403 | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Birmingham Womens Hospital Birmingham, United Kingdom, B15 2TG | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Fukushima Medical University Hospital Fukushima, Japan, 960-1295 | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Saitama Children's Medical Center Saitama, Japan, 330-8777 | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Tokyo Metropolitan Bokutoh Hospital Sumida-ku, Japan, 130-8575 | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Tokyo Metropolitan Ohtsuka Hospital Toshima-ku, Japan, 170-8476 | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Tokyo Metropolitan Children's Medical Center Fuchu, Japan, 183-8561 | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Fukuoka University Hospital Fukuoka, Japan, 814-0180 | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Kyushu University Hospital Fukuoka, Japan, 812-8582 | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Kurume University Hospital Kurume, Japan, 830-0011 | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations University of Occupational and Environmental Health Kitakyushu, Japan, 807-8556 | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Okinawa Prefectural Nanbu Medical Center and Children's MC Shimajiri-gun, Japan, 901-1193 | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Showa University Hospital Shinagawa, Japan, 142-8666 | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Maxima Medisch Centrum, locatie Veldhoven VELDHOVEN, Netherlands, 5504 DB | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Hospital das Clínicas de Botucatu - UNESP Botucatu Botucatu, Brazil, 18618 970 | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Hospital Kuala Lumpur Kuala Lumpur, Malaysia, 50586 | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Spitalul Clinic de Obstretica si Ginecologie "Cuza Voda" Iasi, Romania, 700038 | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Clinical Emergency County Hospital Cluj-Napoca, Romania, 400006 | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations KK Women's and Children's Hospital Singapore, Singapore, 229899 | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Many Locations Many Locations, Argentina | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Many Locations Many Locations, Austria | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Many Locations Many Locations, Belgium | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Many Locations Many Locations, Bulgaria | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Many Locations Many Locations, Brazil | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Many Locations Many Locations, Czech Republic | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Many Locations Many Locations, Spain | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Many Locations Many Locations, United Kingdom | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Many Locations Many Locations, Greece | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Many Locations Many Locations, Hong Kong, China | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Many Locations Many Locations, Hungary | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Many Locations Many Locations, Israel | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Many Locations Many Locations, Italy | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Many Locations Many Locations, Japan | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Many Locations Many Locations, South Korea | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Many Locations Many Locations, Malaysia | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Many Locations Many Locations, Netherlands | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Many Locations Many Locations, Poland | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Many Locations Many Locations, Portugal | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Many Locations Many Locations, Romania | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Many Locations Many Locations, Russia | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Many Locations Many Locations, Sweden | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Many Locations Many Locations, Singapore | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Many Locations Many Locations, Slovakia | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Many Locations Many Locations, Turkey | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Many Locations Many Locations, Taiwan, China | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Locations Many Locations Many Locations, Ukraine | Status Completed | Contact Us: E-mail: [email protected] Phone: (+)1-888-84 22937 |
Trial Design
Open-label, randomized, two–arm, controlled study to assess the efficacy, safety, and tolerability of intravitreal (IVT) aflibercept compared to laser photocoagulation in patients with retinopathy of prematurity (ROP)
Trial Type:
Interventional
Intervention Type:
Drug
Trial Purpose:
Treatment
Allocation:
Randomized
Blinding:
N/A
Assignment:
Parallel Assignment
Trial Arms:
2
Primary Outcome
- Proportion of participants with absence of active ROP and unfavorable structural outcomesActive ROP was defined as ROP requiring treatment. Unfavorable structural outcomes included retinal detachment, macular dragging, macular fold, or retrolental opacity.Timeframe: At 24 weeks after starting study treatment
Secondary Outcome
- Proportion of participants requiring intervention with a second treatment modalityA second treatment modality for ROP was either rescue treatment or any other surgical or nonsurgical treatment for ROP (e.g. IVT anti-VEGF injection, ablative laser therapy, cryotherapy, or vitrectomy) captured as concomitant medication or surgery after study start.Timeframe: From baseline (treatment) up to week 24.
- Proportion of participants with recurrence of ROPParticipants with recurrence of ROP were defined as subjects requiring re-treatment or rescue treatment after in the past the absence of treatment-requiring active ROP had been confirmed by the investigator.Timeframe: From baseline (treatment) up to week 24.
- Exploration of ROP activity scale proposed by the International Neonatal ConsortiumEyes were evaluated for change in ROP activity scale proposed by the International Neonatal Consortium (2018). ROP Activity Scale value range is from 0 to 22. Value 0 to 7 are considered mild, 8 to 12 are moderate, and 13 to 22 are severe. Value 0 means the best and value 22 means the worst. Eyes evaluation was done at baseline and each visit.Timeframe: From baseline (treatment) up to week 24.
- Percentage of participants with ocular Treatment-emergent Adverse Events (TEAEs)A treatment-emergent adverse event (TEAE) was defined as an adverse event (AE) that was observed or reported after the first and not later than 30 days after the last administration of study treatment. Participants treated after week 21 were followed-up for adverse events up to week 28. Ocular TEAEs in treated eyes only were reportedTimeframe: From baseline (treatment) up to week 24
- Percentage of participants with ocular Serious Adverse Events (SAEs)Participants treated after week 21 were followed-up for adverse events up to week 28. Ocular SAEs in treated eyes only were reported.Timeframe: From baseline (treatment) up to week 24
- Percentage of participants with systemic TEAEsA treatment-emergent adverse event (TEAE) was defined as an adverse event (AE) that was observed or reported after the first and not later than 30 days after the last administration of study treatment. Participants treated after week 21 were followed-up for adverse events up to week 28. Systemic TEAEs only were reported.Timeframe: From baseline (treatment) up to week 24
- Percentage of participants with systemic SAEsParticipants treated after week 21 were followed-up for adverse events up to week 28. Systemic SAEs only were reported.Timeframe: From baseline (treatment) up to week 24
- Concentrations of free aflibercept in plasmaBlood samples for determination of aflibercept concentrations in plasma were collected in the aflibercept 0.4 mg arm at Day 1 (within 24 hours after injection), and at weeks 2 and 4, and if feasible also at weeks 8, 12 and 24. Statistics for week 8, 12, 24 not calculated as > 1/3 of the concentrations were below the lower limit of quantification. Free Aflibercept Concentrations in Plasma were only measured in the Aflibercept 0.4 mg treatment arm.Timeframe: From Day 1 up to week 24.
- Number of participants with anti-drug antibodies (ADA)Immunogenicity was characterized by anti-drug antibody (ADA) responses in patients in the aflibercept 0.4 mg arm. Serum samples were taken at baseline prior to the injection and at 12 weeks after injection. ADA titers were summarized for 3 categories: Low (titer <1,000); Moderate (1,000 ≤ titer ≤ 10,000); High (titer >10,000). ADA in serum were only measured in the Aflibercept 0.4 mg treatment arm.Timeframe: Baseline (treatment) and 12 weeks after aflibercept injection
- Number of participants with potential neutralizing antibodies (NAb)NAb status was evaluated for the samples that were positive in the ADA assay and had sufficient volume to analyze. NAb were only measured in participants with positive ADA in the Aflibercept 0.4 mg treatment armTimeframe: At 12 weeks after aflibercept injection
- Number of aflibercept administrationsTotal number of injections in both eyes.Timeframe: From baseline (treatment) up to week 24.
- Number of laser treatmentsTotal number of laser treatment in both eyes. If multiple sessions of laser treatment were necessary within 1 week from baseline, they were counted as a single treatment.Timeframe: From baseline (treatment) up to week 24.
Additional Information
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