check_circleStudy Completed

Retinopathy of prematurity (ROP)

Bayer Identifier:

20090

ClinicalTrials.gov Identifier:

NCT04004208

EudraCT Number:

2018-002611-99

EU CT Number:

Not Available
Aflibercept for retinopathy of prematurity – intravitreal injection versus laser therapy

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.

Key Participants Requirements

Sex

All

Age

NaN - 32 Weeks
  • - 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.
  • - 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
113
Trial Dates
September 2019 - February 2021
Phase
Phase 3
Could I Receive a placebo
No
Products
Eylea (Aflibercept, VEGF Trap-Eye, BAY86-5321)
Accepts Healthy Volunteer
No

Where to participate

StatusInstitutionLocation
Completed
Hacettepe Universitesi Tip FakultesiAnkara, 06100, Turkey
Completed
Baskent Universitesi Tip Fakultesi HastanesiAnkara, 06490, Turkey
Completed
Eskisehir Osmangazi Universitesi Tip FakultesiEskisehir, 26480, Turkey
Withdrawn
Hospital of LT University of Health Sciences Kaunas ClinicsKaunas, LT-50161, Lithuania
Completed
Saglik Bilimleri Universitesi Antalya EA HastanesiAntalya, 07100, Turkey
Withdrawn
A.O.U.I. VeronaVerona, 37126, Italy
Completed
Fondazione Policlinico Universitario Agostino Gemelli IRCCSRoma, 00168, Italy
Completed
IRCCS Ospedale Pediatrico Bambino GesùRoma, 00165, Italy
Completed
A.O. di PerugiaPerugia, 06129, Italy
Completed
Fondazione IRCCS Ca' Granda Ospedale Maggiore PoliclinicoMilano, 20122, Italy
Withdrawn
UZ Leuven GasthuisbergLEUVEN, 3000, Belgium
Completed
S.B.U. Adana Sehir Egitim ve Arastirma HastanesiAdana, 4522, Turkey
Completed
Gazi Universitesi Tip FakultesiAnkara, 06500, Turkey
Withdrawn
Hospital de Sant Joan de DéuEsplugues de LLobregat, 08950, Spain
Completed
Hospital Regional de MálagaMálaga, 29011, Spain
Withdrawn
Medizinische Universität GrazGraz, 8036, Austria
Completed
Kepler Universitätsklinikum Campus IIILinz, 4021, Austria
Completed
Samsung Medical CenterSeoul, 06351, Korea, Republic Of
Completed
Asan Medical CenterSeoul, 05505, Korea, Republic Of
Completed
Soon Chun Hyang University Cheonan HospitalCheonan-si, Korea, Republic Of
Withdrawn
Klinikum Klagenfurt am WörtherseeKlagenfurt, 9020, Austria
Completed
Queen Mary HospitalHong Kong, Hong Kong
Completed
Kaplan Medical CenterRehovot, 7661041, Israel
Withdrawn
Rambam Health CorporationHaifa, 3109601, Israel
Withdrawn
Acibadem Saglik Hizmetleri ve Tic. A.SIstanbul, 34140, Turkey
Withdrawn
Inselspital Universitätsspital BernBern, 3010, Switzerland
Completed
Acibadem City Clinic Multiprofile Hospital for Active TreatmSofia, 1407, Bulgaria
Completed
UMHAT Sveti GeorgiPlovdiv, 4002, Bulgaria
Completed
II SOGHAT SheinovoSofia, 1504, Bulgaria
Completed
SHOGAT Prof Dimitar StamatovVarna, 9000, Bulgaria
Withdrawn
Universitätsklinikum GreifswaldGreifswald, 17475, Germany
Withdrawn
Augenzentrum am St. Franziskus-HospitalMünster, 48145, Germany
Withdrawn
Universitätsklinikum KölnKöln, 50924, Germany
Withdrawn
Universitätsklinikum Carl Gustav Carus DresdenDresden, 01307, Germany
Withdrawn
Medizinische Einrichtungen der Universität BonnBonn, 53105, Germany
Completed
Hospital Prof. Dr. Fernando FonsecaAmadora, 2720-276, Portugal
Withdrawn
Hospital Beatriz AngeloLoures, 2674-514, Portugal
Completed
CHLO - Hospital Sao Francisco XavierLisboa, 1449-005, Portugal
Withdrawn
Clalit Health Services Schneider Children's Medical CenterPetach Tikva, 4920235, Israel
Withdrawn
Luzerner KantonsspitalLuzern, 6000, Switzerland
Withdrawn
Eberhard-Karls-Universität TübingenTübingen, 72076, Germany
Withdrawn
Manchester Eye HospitalManchester, M13 9WH, United Kingdom
Completed
Hospital Universitario "La Paz"Madrid, 28046, Spain
Completed
Hospital Universitario 12 de OctubreMadrid, 28041, Spain
Withdrawn
Hospital Universitari Son EspasesPalma de Mallorca, 07120, Spain
Withdrawn
Hospital for Sick ChildrenToronto, M5G 1X8, Canada
Completed
AZ St-Jan Brugge Oostende AVBRUGGE, 8000, Belgium
Completed
Vseobecna fakultni nemocnice v PrazePraha 2, 12808, Czechia
Completed
Fakultni nemocnice OstravaOstrava, 708 52, Czechia
Withdrawn
Hadassah University Hospital Mount ScopusJerusalem, 9124001, Israel
Withdrawn
Tel-Aviv Sourasky Medical CenterTel Aviv, 6423906, Israel
Withdrawn
Hospital Garcia de OrtaAlmada, 2801-951, Portugal
Completed
EKBC, Uj Szent Janos Korhaz es SzakrendeloBudapest, 1125, Hungary
Withdrawn
Debreceni Egyetem Klinikai KozpontDebrecen, 4032, Hungary
Completed
UNIFESP/EPMSao Paulo, 04023-061, Brazil
Withdrawn
Hospital Municipal Vila Santa CatarinaSão Paulo, 04377-038, Brazil
Completed
FGBUZ "NPC of special children care n.a. Voino-Yaseneckogo"Moscow, 119620, Russian Federation
Withdrawn
FBSI IRTC Eye Microsurgery n.a. acad. S.N. FyodorovMoscow, 127486, Russian Federation
Completed
FSAI NMRC IRTC "Eye Microsurgery", Kaluga’s BranchKaluga, 248007, Russian Federation
Completed
Pediatric Medical UniversitySaint-Petersburg, 194100, Russian Federation
Completed
City Children Hospital ¿1Saint-Petersburg, 198205, Russian Federation
Completed
Narodny ustav detskych chorobBratislava, 833 41, Slovakia
Completed
MI"Odesa Regional Children's Clinical Hospital"Odesa, 65031, Ukraine
Withdrawn
National Pediatric Specialized Hospital "Okhmatdyt"Kyiv, 01135, Ukraine
Completed
Kaohsiung Medical University Chung-Ho Memorial HospitalKaohsiung, 80756, Taiwan
Withdrawn
Chang Gung Memorial Hospital at LinkouTaoyuan, 333423, Taiwan
Completed
Mackay Memorial HospitalTaipei, 10449, Taiwan
Withdrawn
Tallinn Children´s HospitalTallinn, 13419, Estonia
Withdrawn
Children's Clinical University HospitalRiga, LV1004, Latvia
Completed
Ginekologiczno-Polozniczy SK UM im. K. MarcinkowskiegoPoznan, 60-535, Poland
Withdrawn
Hospital de Niños Sor María LudovicaLa Plata, 1900, Argentina
Withdrawn
Hospital Maternal Nuestra Señora del PilarPilar, Argentina
Withdrawn
Inst. de Mater. y Gineco. Nuestra Señora de las MercedesSan MIguel de Tucumán, Argentina
Completed
Hospital Público Descentralizado "Dr. Guillermo Rawson"San Juan, 5400, Argentina
Withdrawn
Sanatorio ArgentinoSan Juan, J5400ANI, Argentina
Completed
Russian National Scientific Medical UniversityMoscow, 117997, Russian Federation
Completed
Sahlgrenska UniversitetssjukhusetGöteborg, Sweden
Withdrawn
Lunds UniversitetssjukhusLund, 221 85, Sweden
Withdrawn
S:t Eriks ÖgonsjukhusStockholm, 112 82, Sweden
Completed
P & A KYRIAKOU Children's HospitalAthens, 11527, Greece
Completed
University General Hospital of IoanninaIoannina, 45500, Greece
Completed
Papageorgiou General Hospital of ThessalonikiThessaloniki, 56403, Greece
Withdrawn
Universitätsklinikum AKH WienWien, 1090, Austria
Completed
Birmingham Womens HospitalBirmingham, B15 2TG, United Kingdom
Withdrawn
Sapporo City General HospitalSapporo, 060-8604, Japan
Completed
Fukushima Medical University HospitalFukushima, 960-1295, Japan
Completed
Saitama Children's Medical CenterSaitama, 330-8777, Japan
Completed
Tokyo Metropolitan Bokutoh HospitalSumida-ku, 130-8575, Japan
Completed
Tokyo Metropolitan Ohtsuka HospitalToshima-ku, 170-8476, Japan
Withdrawn
Tokyo Women's Medical University Yachiyo Medical CenterYachiyo, 276-8524, Japan
Withdrawn
National Center for Child Health and DevelopmentSetagaya, 157-8535, Japan
Withdrawn
Toho University Omori Medical CenterOta-ku, 143-8541, Japan
Completed
Tokyo Metropolitan Children's Medical CenterFuchu, 183-8561, Japan
Withdrawn
Yokohama City University Medical CenterYokohama, 232-0024, Japan
Withdrawn
Hamamatsu University HospitalHamamatsu, 431-3192, Japan
Withdrawn
Nagoya University HospitalNagoya, 466-8560, Japan
Withdrawn
Shiga University of Medical Science HospitalOtsu, 520-2192, Japan
Completed
Fukuoka University HospitalFukuoka, 814-0180, Japan
Completed
Kyushu University HospitalFukuoka, 812-8582, Japan
Completed
Kurume University HospitalKurume, 830-0011, Japan
Completed
University of Occupational and Environmental HealthKitakyushu, 807-8556, Japan
Completed
Okinawa Prefectural Nanbu Medical Center and Children's MCShimajiri-gun, 901-1193, Japan
Withdrawn
Showa University East HospitalShinagawa-ku, 142-0054, Japan
Withdrawn
Fujita Health University HospitalToyoake, 470-1192, Japan
Withdrawn
Hiroshima City Hiroshima Citizens HospitalHiroshima, 730-8518, Japan
Withdrawn
Nara Medical University HospitalKashihara, 634-8522, Japan
Withdrawn
Juntendo University Urayasu HospitalUrayasu, 279-0021, Japan
Completed
Showa University HospitalShinagawa, 142-8666, Japan
Withdrawn
IWK Health CentreHalifax, B3K 6R8, Canada
Completed
Maxima Medisch Centrum, locatie VeldhovenVELDHOVEN, 5504 DB, Netherlands
Withdrawn
Karolinska Universitetssjukhuset Huddinge StockholmStockholm, S-141 86, Sweden
Withdrawn
Shamir Medical Center (Assaf Harofeh)Zerifin, 6093000, Israel
Withdrawn
CHUP - Hospital Santo AntonioPorto, 4099-001, Portugal
Withdrawn
ULSM - Hospital Pedro HispanoMatosinhos, 4464-513, Portugal
Completed
Hospital das Clínicas de Botucatu - UNESP BotucatuBotucatu, 18618 970, Brazil
Completed
Hospital Kuala LumpurKuala Lumpur, 50586, Malaysia
Withdrawn
University Hospital Kebangsaan MalaysiaKuala Lumpur, 56000, Malaysia
Withdrawn
Hopital Necker les enfants malades - ParisPARIS, 75015, France
Withdrawn
Hôpital Pellegrin - BordeauxBORDEAUX, 33076, France
Withdrawn
Hôpital Arnaud de Villeneuve - MontpellierMONTPELLIER, 34059, France
Withdrawn
Fondation A. de Rotschild - ParisPARIS CEDEX 19, 75940, France
Withdrawn
Municipal Clinical Emergency Hospital of TimisoaraTimisoara, 300172, Romania
Completed
Spitalul Clinic de Obstretica si Ginecologie "Cuza Voda"Iasi, 700038, Romania
Completed
Clinical Emergency County HospitalCluj-Napoca, 400006, Romania
Withdrawn
Hospital de Clínicas de Porto AlegrePorto Alegre, Brazil
Completed
KK Women's and Children's HospitalSingapore, 229899, Singapore
Withdrawn
Vivantes Klinikum NeuköllnBerlin, 12351, Germany
Completed
Many LocationsMany Locations, Argentina
Completed
Many LocationsMany Locations, Austria
Completed
Many LocationsMany Locations, Belgium
Completed
Many LocationsMany Locations, Bulgaria
Completed
Many LocationsMany Locations, Brazil
Withdrawn
Many LocationsMany Locations, Canada
Withdrawn
Many LocationsMany Locations, Switzerland
Completed
Many LocationsMany Locations, Czechia
Withdrawn
Many LocationsMany Locations, Germany
Withdrawn
Many LocationsMany Locations, Estonia
Completed
Many LocationsMany Locations, Spain
Withdrawn
Many LocationsMany Locations, France
Completed
Many LocationsMany Locations, United Kingdom
Completed
Many LocationsMany Locations, Greece
Completed
Many LocationsMany Locations, Hong Kong
Completed
Many LocationsMany Locations, Hungary
Completed
Many LocationsMany Locations, Israel
Completed
Many LocationsMany Locations, Italy
Completed
Many LocationsMany Locations, Japan
Completed
Many LocationsMany Locations, Korea, Republic Of
Withdrawn
Many LocationsMany Locations, Lithuania
Withdrawn
Many LocationsMany Locations, Latvia
Completed
Many LocationsMany Locations, Malaysia
Completed
Many LocationsMany Locations, Netherlands
Completed
Many LocationsMany Locations, Poland
Completed
Many LocationsMany Locations, Portugal
Completed
Many LocationsMany Locations, Romania
Completed
Many LocationsMany Locations, Russian Federation
Completed
Many LocationsMany Locations, Sweden
Completed
Many LocationsMany Locations, Singapore
Completed
Many LocationsMany Locations, Slovakia
Completed
Many LocationsMany Locations, Turkey
Completed
Many LocationsMany Locations, Taiwan
Completed
Many LocationsMany Locations, Ukraine

Primary Outcome

  • 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.
    date_rangeTime Frame:
    At 24 weeks after starting study treatment

Secondary Outcome

  • Proportion of participants requiring intervention with a second treatment modality
    A 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.
    date_rangeTime Frame:
    From baseline (treatment) up to week 24.
  • Proportion of participants with recurrence of ROP
    Participants 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.
    date_rangeTime Frame:
    From baseline (treatment) up to week 24.
  • Exploration of ROP activity scale proposed by the International Neonatal Consortium
    Eyes 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.
    date_rangeTime Frame:
    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 reported
    date_rangeTime Frame:
    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.
    date_rangeTime Frame:
    From baseline (treatment) up to week 24
  • Percentage of participants with systemic 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. Systemic TEAEs only were reported.
    date_rangeTime Frame:
    From baseline (treatment) up to week 24
  • Percentage of participants with systemic SAEs
    Participants treated after week 21 were followed-up for adverse events up to week 28. Systemic SAEs only were reported.
    date_rangeTime Frame:
    From baseline (treatment) up to week 24
  • Concentrations of free aflibercept in plasma
    Blood 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.
    date_rangeTime Frame:
    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.
    date_rangeTime Frame:
    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 arm
    date_rangeTime Frame:
    At 12 weeks after aflibercept injection
  • Number of aflibercept administrations
    Total number of injections in both eyes.
    date_rangeTime Frame:
    From baseline (treatment) up to week 24.
  • Number of laser treatments
    Total 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.
    date_rangeTime Frame:
    From baseline (treatment) up to week 24.

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

Additional Information

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