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A Clinical Efficacy and Safety Study of OHB-607 in Preventing Bronchopulmonary Dysplasia in Extremely Premature Infants

Phase 2
Recruiting
Conditions
Intraventricular Hemorrhage
Retinopathy of Prematurity (ROP)
Bronchopulmonary Dysplasia
Chronic Lung Disease of Prematurity
Interventions
Registration Number
NCT03253263
Lead Sponsor
OHB Neonatology Ltd.
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
338
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
OHB-607OHB-607Participants will receive continuous IV infusion of OHB-607 through from birth up to PMA 29 weeks +6 days.
Primary Outcome Measures
NameTimeMethod
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.Baseline through 36 weeks postmenstrual age (PMA)

Severe BPD is defined by the modified NICHD severity grading

Secondary Outcome Measures
NameTimeMethod
Chronic respiratory morbidity outcomes at 24 months CA24 months CA
Incidence and severity of BPDBaseline through 36 weeks postmenstrual age (PMA)

BPD severity is defined by the modified NICHD severity grading

Neurodevelopment outcomesFrom 6 months CA through 24 months CA

Neurodevelopmental impairment, Physical and cognitive development will be measured by ASQ®-3 administered at 12 and 24 months CA.

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.Baseline until 12 months CA using CLDPSS
Incidence and severity of IVHBaseline through 36 weeks postmenstrual age (PMA)

Incidence of all grades of IVH as assessed by centrally read CUS and classified according to the Volpe criteria

Mortality from randomization through to 24 months CAFrom birth through 24 months CA

Mortality rates from randomization to initial hospital discharge and from initial discharge through 24 months CA.

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., 201936 weeks weeks postmenstrual age (PMA) (± 3 days)
Exposure-response relationship between measured IGF-1 and Retinopathy of Prematurity (ROP)Baseline through 40 weeks PMA

Blood samples will be collected to measure IGF-1 and these measured values will be associated with the incidence and severity grade of ROP

Incidence of Retinopathy of Prematurity (ROP)Baseline through 40 weeks PMA

ROP is classified according to the International Classification

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.Baseline through 12 months CA

The final weaning off of RTS is defined as the 7th consecutive day that the subject is off RTS.

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.Time Frame: Baseline through 36 weeks postmenstrual age (PMA)

Severe BPD is defined based on the classification according to Jensen et al., 2019

Occurrence of severe (Grade 3 and 4) intraventricular hemorrhage (IVH) before 40 weeks PMA, as assessed by cranial ultrasound as compared to the SNC groupBaseline through 40 weeks postmenstrual age (PMA)

Severe IVH as classified according to the Volpe criteria

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 groupBaseline through 40 weeks postmenstrual age (PMA)
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.Time Frame: Determined by the separate BSID III scales at 24 months CA
Exposure-response relationship between measured IGF-1 and Bronchopulmonary Dysplasia (BPD)Baseline through 36 weeks PMA

Blood samples will be collected to measure IGF-1 and these measured values will be associated with the incidence and severity grade of BPD

Exposure-response relationship between measured IGF-1 and intraventricular hemorrhage (IVH)Baseline through 40 weeks PMA

Blood samples will be collected to measure IGF-1 and these measured values will be associated with the incidence and severity grade of IVH

Exposure-response relationship between measured IGF-1 and necrotizing enterocolitis (NEC)Baseline through 40 weeks PMA

Blood samples will be collected to measure IGF-1 and these measured values will be associated with the incidence and severity grade of NEC

To assess the safety profile of OHB-607 as compared to the SNC group.Baseline through 24 months CA

Incidence, severity, and causality assessment of Adverse Events (AEs) and Serious Adverse Events (SAEs), including Fatal AEs as per the neonatal adverse event severity scale.

Trial Locations

Locations (61)

Arkansas Children's Hospital

🇺🇸

Little Rock, Arkansas, United States

University of Arkansas for Medical Sciences

🇺🇸

Little Rock, Arkansas, United States

Children's Hospital of Orange County

🇺🇸

California City, California, United States

LAC USC Medical Center

🇺🇸

Los Angeles, California, United States

Jackson Memorial Hospital

🇺🇸

Miami, Florida, United States

Tampa General Hospital

🇺🇸

Tampa, Florida, United States

University of Illinois at Chicago

🇺🇸

Chicago, Illinois, United States

Riley Hospital for Children

🇺🇸

Indianapolis, Indiana, United States

Memorial Hospital of South Bend

🇺🇸

South Bend, Indiana, United States

Norton Children's Hospital

🇺🇸

Louisville, Kentucky, United States

Ochsner Baptist Medical Center

🇺🇸

New Orleans, Louisiana, United States

Tufts Medical Center

🇺🇸

Boston, Massachusetts, United States

Boston Children's Hospital

🇺🇸

Boston, Massachusetts, United States

Children's Minnesota - Children's Hospital and Clinics - St. Paul

🇺🇸

Saint Paul, Minnesota, United States

Children's Minnesota - Children's Hospital and Clinics

🇺🇸

Saint Paul, Minnesota, United States

University of Mississippi Medical Center

🇺🇸

Jackson, Mississippi, United States

University of Rochester

🇺🇸

Rochester, New York, United States

Maria Fareri Children's Hospital

🇺🇸

Valhalla, New York, United States

Nationwide Children's Hospital

🇺🇸

Columbus, Ohio, United States

University of Oklahoma Health Sciences Center

🇺🇸

Oklahoma City, Oklahoma, United States

Medical University of South Carolina Children Hospital

🇺🇸

Charleston, South Carolina, United States

UVA Children's Hospital

🇺🇸

Charlottesville, Virginia, United States

Virginia Commonwealth University - Children's Hospital of Richmond at VCU

🇺🇸

Richmond, Virginia, United States

Sainte Justine Hospital

🇨🇦

Montreal, Quebec, Canada

Mount Sinai Hospital

🇨🇦

Toronto, Canada

Oulun Yliopistollinen Sairaala

🇫🇮

Oulu, Finland

Hôpital Antoine Béclère

🇫🇷

Clamart, Hauts-de-Seine, France

Groupe Hospitalier Necker Enfants Malades

🇫🇷

Paris, France

Universitätsklinikum Freiburg

🇩🇪

Freiburg, Baden-Württemberg, Germany

Universitatsklinikum Leipzig

🇩🇪

Leipzig, Sachsen, Germany

Klinikum Nürnberg

🇩🇪

Nürnberg, Germany

Cork University Maternity Hospital

🇮🇪

Cork, Wilton, Ireland

Fondazione Policlinico Universitario A Gemelli

🇮🇹

Roma, Lazio, Italy

Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico

🇮🇹

Milano, Lombardia, Italy

Azienda Ospedaliera Di Padova

🇮🇹

Padova, Veneto, Italy

Azienda Ospedaliero-Universitaria Careggi SOD Neonatologia e Terapia Intensiva Neonatale

🇮🇹

Firenze, Italy

Istituto Giannina Gaslini-Istituto Pediatrico di Ricovero e

🇮🇹

Genova, Italy

Presidio Ospedaliero Di Treviso Ca' Foncello

🇮🇹

Treviso, Italy

Kagoshima City Hospital

🇯🇵

Kagoshima-shi, Kagosima, Japan

Nagano Children's Hospital

🇯🇵

Azumino, Nagano, Japan

Kurashiki Central Hospital

🇯🇵

Kurashiki-shi, Okayama, Japan

Saitama Medical Center

🇯🇵

Kawagoe-shi, Saitama, Japan

Osaka Women's and Children's Hospital

🇯🇵

Izumi, Ôsaka, Japan

Maastricht University Medical Center

🇳🇱

Maastricht, Limburg, Netherlands

Academisch Medisch Centrum Amsterdam

🇳🇱

Amsterdam-Zuidoost, Noord-Holland, Netherlands

Wilhelmina Children Hospital-University Medical Center Utrecht

🇳🇱

Utrecht, Netherlands

Hospital Garcia de Orta

🇵🇹

Almada, Portugal

Maternidade Alfredo da Costa

🇵🇹

Lisboa, Portugal

Centro Hospitalar Lisboa

🇵🇹

Lisboa, Portugal

Centro Materno Infantil do Norte - Centro Hospital Universitario do Porto, E.P.E.

🇵🇹

Porto, Portugal

Hospital General Universitario Dr. Balmis

🇪🇸

Alicante, Spain

Skanes Universitetssjukhus

🇸🇪

Lund, Sweden

Karolinska Solna

🇸🇪

Stockholm, Sweden

Norfolk and Norwich University Hospital

🇬🇧

Norwich, Norfolk, United Kingdom

Ashford and St. Peter's Hospitals NHS Trust - St. Peter's Hospital

🇬🇧

Chertsey, Surrey, United Kingdom

University of Cambridge

🇬🇧

Cambridge, United Kingdom

University Hospital Coventry

🇬🇧

Coventry, United Kingdom

Liverpool Women's Hospital - PPDS

🇬🇧

Liverpool, United Kingdom

University College London

🇬🇧

London, United Kingdom

Chelsea and Westminster NHS Trust

🇬🇧

London, United Kingdom

St. Mary's Hospital

🇬🇧

Manchester, United Kingdom

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