Clinical trial NCT03253263: A Clinical Efficacy and Safety Study of OHB-607 in Preventing Bronchopulmonary Dysplasia in Extremely Premature Infants
Official title: A Phase 2b, Multicenter, Randomized, Open-label, Two-Arm Study to Evaluate the Clinical Efficacy and Safety of OHB-607 Compared to Standard Neonatal Care for the Prevention of Bronchopulmonary Dysplasia, the Most Common Cause of Chronic Lung Disease of Prematurity
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Bronchopulmonary Dysplasia
Chronic Lung Disease of Prematurity
Intraventricular Hemorrhage
Retinopathy of Prematurity (ROP)
Lead sponsor: Oak Hill Bio Ltd
Sponsor class: INDUSTRY
First posted: 2017-08-17
Enrollment: 338
Sex: ALL
Minimum age (years): 0
Maximum age (years): 24
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to determine if an investigational drug can prevent Bronchopulmonary Dysplasia, reducing the burden of chronic lung disease in extremely premature infants, as compared to extremely premature infants receiving standard neonatal care alone.


Eligibility criteria: Inclusion Criteria:

1. Written informed consents and/or assents must be signed and dated by the participant's parent(s) prior to any study related procedures. The informed consent and any assents for underage parents must be approved by the IRB/IEC (in accordance with local regulations).
2. Written informed consents and/or assents must be signed and dated by the participant's birth mother prior to providing study-related information related to birth mother medical history, pregnancy and the birth of the participant. The informed consent and any assents for underage birth mothers must be approved by the IRB/IEC (in accordance with local regulations).
3. Subjects must be between 23 weeks +0 days and 27 weeks +6 days GA, inclusive.

Exclusion Criteria:

1. Detectable major (or severe) congenital malformation identified before randomization.
2. Known or suspected chromosomal abnormality, genetic disorder, or syndrome, identified before randomization, according to the investigator's opinion.
3. Hypoglycemia at Baseline (blood glucose less than (\<) 45 milligrams per deciliter \[mg/dL\] or 2.5 milli moles per liter \[mmol/L\]) which persists in spite of glucose supplementation, to exclude severe congenital abnormalities of glucose metabolism.
4. Clinically significant neurological disease identified before randomization according to cranial ultrasound (hemorrhages confined to the germinal matrix are allowed) and investigator's opinion.
5. Any other condition or therapy that, in the investigator's opinion, may pose a risk to the participant or interfere with the participant's potential compliance with this protocol or interfere with interpretation of results.
6. Current or planned participation in a clinical study of another investigational study treatment, device, or procedure (participation in non-interventional studies is permitted on a case-by-case basis).
7. The participant or participant's parent(s) is/are unable to comply with the protocol or is unlikely to be available for long-term follow-up as determined by the investigator.
8. Birth mother with active COVID-19 infection at birth or a history of severe COVID-19 infection (requiring intensive care hospitalization) during pregnancy.

Primary outcomes:
measure: Reduction in the incidence of severe Bronchopulmonary Dysplasia (BPD) at 36 weeks (±3 days) Postmenstrual Age (PMA), or death at or before 36 weeks PMA, whichever comes first as compared to the SNC group.
timeFrame: Baseline through 36 weeks postmenstrual age (PMA)
Secondary outcomes:
measure: Reducing the burden of Chronic Lung Disease, as indicated by a reduction in time to final weaning off of Respiratory Technology Support (RTS) through 12 months Corrected Age (CA), as compared to the SNC group.
timeFrame: Baseline through 12 months CA
measure: Reduction in the incidence of severe BPD at 36 weeks (±3 days) PMA, or death at or before 36 weeks PMA, whichever comes first as compared to the SNC group.
timeFrame: Time Frame: Baseline through 36 weeks postmenstrual age (PMA)
measure: Occurrence of severe (Grade 3 and 4) intraventricular hemorrhage (IVH) before 40 weeks PMA, as assessed by cranial ultrasound as compared to the SNC group
timeFrame: Baseline through 40 weeks postmenstrual age (PMA)
measure: To assess the effect of OHB-607 on occurrence of severe retinopathy of prematurity (ROP) (Stage 3 and above) up to 40 weeks PMA as compared to the SNC group
timeFrame: Baseline through 40 weeks postmenstrual age (PMA)
measure: To assess the effect of OHB-607 on chronic respiratory outcomes as measured by the Chronic Lung Disease Prematurity Severity Score (CLDPSS) as compared to the SNC group at 12 months CA.
timeFrame: Baseline until 12 months CA using CLDPSS
measure: The effect of OHB-607 on neurodevelopment is measured by the Cognitive, Language and Motor Scales of the Bayley Scales of Infant and Toddler Development (BSID) III as compared to the SNC group at 24 months CA.
timeFrame: Time Frame: Determined by the separate BSID III scales at 24 months CA
measure: Chronic respiratory morbidity outcomes at 24 months CA
timeFrame: 24 months CA
measure: Incidence and severity of BPD
timeFrame: Baseline through 36 weeks postmenstrual age (PMA)
measure: Jensen BPD grade at 36 weeks PMA (± 3 days), as classified according to Jensen et al., 2019. Incidence of all severity grades of BPD as assessed by Jensen et al., 2019
timeFrame: 36 weeks weeks postmenstrual age (PMA) (± 3 days)
measure: Incidence and severity of IVH
timeFrame: Baseline through 36 weeks postmenstrual age (PMA)
measure: Neurodevelopment outcomes
timeFrame: From 6 months CA through 24 months CA
measure: Incidence of Retinopathy of Prematurity (ROP)
timeFrame: Baseline through 40 weeks PMA
measure: Mortality from randomization through to 24 months CA
timeFrame: From birth through 24 months CA
measure: Exposure-response relationship between measured IGF-1 and Bronchopulmonary Dysplasia (BPD)
timeFrame: Baseline through 36 weeks PMA
measure: Exposure-response relationship between measured IGF-1 and intraventricular hemorrhage (IVH)
timeFrame: Baseline through 40 weeks PMA
measure: Exposure-response relationship between measured IGF-1 and necrotizing enterocolitis (NEC)
timeFrame: Baseline through 40 weeks PMA
measure: Exposure-response relationship between measured IGF-1 and Retinopathy of Prematurity (ROP)
timeFrame: Baseline through 40 weeks PMA
measure: To assess the safety profile of OHB-607 as compared to the SNC group.
timeFrame: Baseline through 24 months CA
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Arkansas Children's Hospital
state: Arkansas
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: California City
country: United States
facility: Children's Hospital of Orange County
state: California
city: Los Angeles
country: United States
facility: LAC USC Medical Center
state: California
city: Miami
country: United States
facility: Jackson Memorial Hospital
state: Florida
city: Tampa
country: United States
facility: Tampa General Hospital
state: Florida
city: Chicago
country: United States
facility: University of Illinois at Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Riley Hospital for Children
state: Indiana
city: South Bend
country: United States
facility: Memorial Hospital of South Bend
state: Indiana
city: Louisville
country: United States
facility: Norton Children's Hospital
state: Kentucky
city: New Orleans
country: United States
facility: Ochsner Baptist Medical Center
state: Louisiana
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Saint Paul
country: United States
facility: Children's Minnesota - Children's Hospital and Clinics - St. Paul
state: Minnesota
city: Saint Paul
country: United States
facility: Children's Minnesota - Children's Hospital and Clinics
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Valhalla
country: United States
facility: Maria Fareri Children's Hospital
state: New York
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Charleston
country: United States
facility: Medical University of South Carolina Children Hospital
state: South Carolina
city: Charlottesville
country: United States
facility: UVA Children's Hospital
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University - Children's Hospital of Richmond at VCU
state: Virginia
city: Montreal
country: Canada
facility: Sainte Justine Hospital
state: Quebec
city: Toronto
country: Canada
facility: Mount Sinai Hospital
city: Oulu
country: Finland
facility: Oulun Yliopistollinen Sairaala
city: Clamart
country: France
facility: Hôpital Antoine Béclère
state: Hauts-de-Seine
city: Paris
country: France
facility: Groupe Hospitalier Necker Enfants Malades
city: Freiburg
country: Germany
facility: Universitätsklinikum Freiburg
state: Baden-Württemberg
city: Leipzig
country: Germany
facility: Universitatsklinikum Leipzig
state: Sachsen
city: Nürnberg
country: Germany
facility: Klinikum Nürnberg
city: Cork
country: Ireland
facility: Cork University Maternity Hospital
state: Wilton
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario A Gemelli
state: Lazio
city: Milano
country: Italy
facility: Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
state: Lombardia
city: Padova
country: Italy
facility: Azienda Ospedaliera Di Padova
state: Veneto
city: Firenze
country: Italy
facility: Azienda Ospedaliero-Universitaria Careggi SOD Neonatologia e Terapia Intensiva Neonatale
city: Genova
country: Italy
facility: Istituto Giannina Gaslini-Istituto Pediatrico di Ricovero e
city: Treviso
country: Italy
facility: Presidio Ospedaliero Di Treviso Ca' Foncello
city: Kagoshima-shi
country: Japan
facility: Kagoshima City Hospital
state: Kagosima
city: Azumino
country: Japan
facility: Nagano Children's Hospital
state: Nagano
city: Kurashiki-shi
country: Japan
facility: Kurashiki Central Hospital
state: Okayama
city: Kawagoe-shi
country: Japan
facility: Saitama Medical Center
state: Saitama
city: Izumi
country: Japan
facility: Osaka Women's and Children's Hospital
state: Ôsaka
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center
state: Limburg
city: Amsterdam-Zuidoost
country: Netherlands
facility: Academisch Medisch Centrum Amsterdam
state: Noord-Holland
city: Utrecht
country: Netherlands
facility: Wilhelmina Children Hospital-University Medical Center Utrecht
city: Almada
country: Portugal
facility: Hospital Garcia de Orta
city: Lisboa
country: Portugal
facility: Maternidade Alfredo da Costa
city: Lisboa
country: Portugal
facility: Centro Hospitalar Lisboa
city: Porto
country: Portugal
facility: Centro Materno Infantil do Norte - Centro Hospital Universitario do Porto, E.P.E.
city: Alicante
country: Spain
facility: Hospital General Universitario Dr. Balmis
city: Lund
country: Sweden
facility: Skanes Universitetssjukhus
city: Stockholm
country: Sweden
facility: Karolinska Solna
city: Norwich
country: United Kingdom
facility: Norfolk and Norwich University Hospital
state: Norfolk
city: Chertsey
country: United Kingdom
facility: Ashford and St. Peter's Hospitals NHS Trust - St. Peter's Hospital
state: Surrey
city: Cambridge
country: United Kingdom
facility: University of Cambridge
city: Coventry
country: United Kingdom
facility: University Hospital Coventry
city: Liverpool
country: United Kingdom
facility: Liverpool Women's Hospital - PPDS
city: London
country: United Kingdom
facility: University College London
city: London
country: United Kingdom
facility: Chelsea and Westminster NHS Trust
city: Manchester
country: United Kingdom
facility: St. Mary's Hospital
Study officials:
References:
citation: Kramer BW, Abman S, Daly M, Jobe AH, Niklas V. Insulin-like growth factor-1 replacement therapy after extremely premature birth: An opportunity to optimize lifelong lung health by preserving the natural sequence of lung development. Paediatr Respir Rev. 2023 Dec;48:24-29. doi: 10.1016/j.prrv.2023.05.001. Epub 2023 May 6.
citation: Ley D, Hallberg B, Hansen-Pupp I, Dani C, Ramenghi LA, Marlow N, Beardsall K, Bhatti F, Dunger D, Higginson JD, Mahaveer A, Mezu-Ndubuisi OJ, Reynolds P, Giannantonio C, van Weissenbruch M, Barton N, Tocoian A, Hamdani M, Jochim E, Mangili A, Chung JK, Turner MA, Smith LEH, Hellstrom A; study team. rhIGF-1/rhIGFBP-3 in Preterm Infants: A Phase 2 Randomized Controlled Trial. J Pediatr. 2019 Mar;206:56-65.e8. doi: 10.1016/j.jpeds.2018.10.033. Epub 2018 Nov 22.
citation: Hellstrom W, Hortensius LM, Lofqvist C, Hellgren G, Tataranno ML, Ley D, Benders MJNL, Hellstrom A, Bjorkman-Burtscher IM, Heckemann RA, Savman K. Postnatal serum IGF-1 levels associate with brain volumes at term in extremely preterm infants. Pediatr Res. 2023 Feb;93(3):666-674. doi: 10.1038/s41390-022-02134-4. Epub 2022 Jun 9.