Clinical trial NCT04004208: Aflibercept for Retinopathy of Prematurity - Intravitreal Injection Versus Laser Therapy
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Retinopathy of Prematurity (ROP)
Lead sponsor: Bayer
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2019-07-01
Enrollment: 113
Sex: ALL
Maximum age (years): 32
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Proportion of Participants With Absence of Active ROP and Unfavorable Structural Outcomes
timeFrame: At 24 weeks after starting study treatment
Secondary outcomes:
measure: Proportion of Participants Requiring Intervention With a Second Treatment Modality
timeFrame: From baseline (treatment) up to week 24.
measure: Proportion of Participants With Recurrence of ROP
timeFrame: From baseline (treatment) up to week 24.
measure: Exploration of ROP Activity Scale Proposed by the International Neonatal Consortium
timeFrame: From baseline (treatment) up to week 24.
measure: Percentage of Participants With Ocular Treatment-emergent Adverse Events (TEAEs)
timeFrame: From baseline (treatment) up to week 24
measure: Percentage of Participants With Ocular Serious Adverse Events (SAEs)
timeFrame: From baseline (treatment) up to week 24
measure: Percentage of Participants With Systemic TEAEs
timeFrame: From baseline (treatment) up to week 24
measure: Percentage of Participants With Systemic SAEs
timeFrame: From baseline (treatment) up to week 24
measure: Concentrations of Free Aflibercept in Plasma
timeFrame: From Day 1 up to week 24.
measure: Number of Participants With Anti-drug Antibodies (ADA)
timeFrame: Baseline (treatment) and 12 weeks after aflibercept injection
measure: Number of Participants With Potential Neutralizing Antibodies (NAb)
timeFrame: At 12 weeks after aflibercept injection
measure: Number of Aflibercept Administrations
timeFrame: From baseline (treatment) up to week 24.
measure: Number of Laser Treatments
timeFrame: From baseline (treatment) up to week 24.
Other outcomes:
Locations:
city: Multiple Locations
country: Argentina
facility: Many Locations
city: San Juan
country: Argentina
facility: Hospital Público Descentralizado "Dr. Guillermo Rawson"
city: Linz
country: Austria
facility: Kepler Universitätsklinikum Campus III
city: Multiple Locations
country: Austria
facility: Many Locations
city: Brugge
country: Belgium
facility: AZ St-Jan Brugge Oostende AV
city: Multiple Locations
country: Belgium
facility: Many Locations
city: Botucatu
country: Brazil
facility: Hospital das Clínicas de Botucatu - UNESP Botucatu
state: Sao Paulo
city: Multiple Locations
country: Brazil
facility: Many Locations
city: Sao Paulo
country: Brazil
facility: Unifesp/Epm
city: Multiple Locations
country: Bulgaria
facility: Many Locations
city: Plovdiv
country: Bulgaria
facility: UMHAT Sveti Georgi
city: Sofia
country: Bulgaria
facility: Acibadem City Clinic Multiprofile Hospital for Active Treatm
city: Sofia
country: Bulgaria
facility: II SOGHAT Sheinovo
city: Varna
country: Bulgaria
facility: SHOGAT Prof Dimitar Stamatov
city: Multiple Locations
country: Czechia
facility: Many Locations
city: Ostrava
country: Czechia
facility: Fakultni nemocnice Ostrava
city: Praha 2
country: Czechia
facility: Vseobecna fakultni nemocnice v Praze
city: Athens
country: Greece
facility: P & A KYRIAKOU Children's Hospital
city: Ioannina
country: Greece
facility: University General Hospital of Ioannina
city: Multiple Locations
country: Greece
facility: Many Locations
city: Thessaloniki
country: Greece
facility: Papageorgiou General Hospital of Thessaloniki
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
city: Multiple Locations
country: Hong Kong
facility: Many Locations
city: Budapest
country: Hungary
facility: EKBC, Uj Szent Janos Korhaz es Szakrendelo
city: Multiple Locations
country: Hungary
facility: Many Locations
city: Multiple Locations
country: Israel
facility: Many Locations
city: Rehovot
country: Israel
facility: Kaplan Medical Center
city: Roma
country: Italy
facility: IRCCS Ospedale Pediatrico Bambino Gesù
state: Lazio
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
state: Lazio
city: Milano
country: Italy
facility: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
state: Lombardia
city: Perugia
country: Italy
facility: A.O. di Perugia
state: Umbria
city: Multiple Locations
country: Italy
facility: Many Locations
city: Kitakyushu
country: Japan
facility: University of Occupational and Environmental Health
state: Fukuoka
city: Kurume
country: Japan
facility: Kurume University Hospital
state: Fukuoka
city: Shimajiri-gun
country: Japan
facility: Okinawa Prefectural Nanbu Medical Center and Children's MC
state: Okinawa
city: Fuchu
country: Japan
facility: Tokyo Metropolitan Children's Medical Center
state: Tokyo
city: Shinagawa
country: Japan
facility: Showa University Hospital
state: Tokyo
city: Sumida-ku
country: Japan
facility: Tokyo Metropolitan Bokutoh Hospital
state: Tokyo
city: Toshima-ku
country: Japan
facility: Tokyo Metropolitan Ohtsuka Hospital
state: Tokyo
city: Fukuoka
country: Japan
facility: Kyushu University Hospital
city: Fukuoka
country: Japan
facility: Fukuoka University Hospital
city: Fukushima
country: Japan
facility: Fukushima Medical University Hospital
city: Multiple Locations
country: Japan
facility: Many Locations
city: Saitama
country: Japan
facility: Saitama Children's Medical Center
city: Cheonan-si
country: Korea, Republic of
facility: Soon Chun Hyang University Cheonan Hospital
state: Chungcheongnamdo
city: Multiple Locations
country: Korea, Republic of
facility: Many Locations
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Kuala Lumpur
country: Malaysia
facility: Hospital Kuala Lumpur
city: Multiple Locations
country: Malaysia
facility: Many Locations
city: Multiple Locations
country: Netherlands
facility: Many Locations
city: Veldhoven
country: Netherlands
facility: Maxima Medisch Centrum, locatie Veldhoven
city: Multiple Locations
country: Poland
facility: Many Locations
city: Poznan
country: Poland
facility: Ginekologiczno-Polozniczy SK UM im. K. Marcinkowskiego
city: Amadora
country: Portugal
facility: Hospital Prof. Dr. Fernando Fonseca
state: Lisboa
city: Lisboa
country: Portugal
facility: CHLO - Hospital Sao Francisco Xavier
city: Multiple Locations
country: Portugal
facility: Many Locations
city: Cluj-Napoca
country: Romania
facility: Clinical Emergency County Hospital
state: Cluj
city: Iasi
country: Romania
facility: Spitalul Clinic de Obstretica si Ginecologie "Cuza Voda"
city: Multiple Locations
country: Romania
facility: Many Locations
city: Kaluga
country: Russian Federation
facility: FSAI NMRC IRTC "Eye Microsurgery", Kaluga's Branch
city: Moscow
country: Russian Federation
facility: Russian National Scientific Medical University
city: Moscow
country: Russian Federation
facility: FGBUZ "NPC of special children care n.a. Voino-Yaseneckogo"
city: Multiple Locations
country: Russian Federation
facility: Many Locations
city: Saint-Petersburg
country: Russian Federation
facility: Pediatric Medical University
city: Saint-Petersburg
country: Russian Federation
facility: City Children Hospital ¿1
city: Multiple Locations
country: Singapore
facility: Many Locations
city: Singapore
country: Singapore
facility: KK Women's and Children's Hospital
city: Bratislava
country: Slovakia
facility: Narodny ustav detskych chorob
city: Multiple Locations
country: Slovakia
facility: Many Locations
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario "La Paz"
city: Multiple Locations
country: Spain
facility: Many Locations
city: Málaga
country: Spain
facility: Hospital Regional de Málaga
city: Göteborg
country: Sweden
facility: Sahlgrenska Universitetssjukhuset
city: Multiple Locations
country: Sweden
facility: Many Locations
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Chung-Ho Memorial Hospital
city: Multiple Locations
country: Taiwan
facility: Many Locations
city: Taipei
country: Taiwan
facility: Mackay Memorial Hospital
city: Adana
country: Turkey
facility: S.B.U. Adana Sehir Egitim ve Arastirma Hastanesi
city: Ankara
country: Turkey
facility: Hacettepe Universitesi Tip Fakultesi
city: Ankara
country: Turkey
facility: Baskent Universitesi Tip Fakultesi Hastanesi
city: Ankara
country: Turkey
facility: Gazi Universitesi Tip Fakultesi
city: Antalya
country: Turkey
facility: Saglik Bilimleri Universitesi Antalya EA Hastanesi
city: Eskisehir
country: Turkey
facility: Eskisehir Osmangazi Universitesi Tip Fakultesi
city: Multiple Locations
country: Turkey
facility: Many Locations
city: Multiple Locations
country: Ukraine
facility: Many Locations
city: Odesa
country: Ukraine
facility: MI"Odesa Regional Children's Clinical Hospital"
city: Birmingham
country: United Kingdom
facility: Birmingham Womens Hospital
city: Multiple Locations
country: United Kingdom
facility: Many Locations
Study officials:
References:
citation: 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.