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

Bronchopulmonary Dysplasia Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03253263
• Other study ID #: OHB-607-202
• Secondary ID: 2018-001393-16jR
• Status: Recruiting
• Phase: Phase 2
• Start date: May 9, 2019
• Est. completion date: January 21, 2028

Study information

• Verified date: May 2024
• Source: Oak Hill Bio Ltd
• Contact: OHB Contact
• Email: CMO[@]Oakhillbio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 338
• Est. completion date: January 21, 2028
• Est. primary completion date: January 23, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 0 Hours to 24 Hours

Eligibility

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.

Related Conditions & MeSH terms

• Bronchopulmonary Dysplasia
• Chronic Lung Disease of Prematurity
• Hemorrhage
• Intraventricular Hemorrhage
• Lung Diseases
• Premature Birth
• Retinopathy of Prematurity
• Retinopathy of Prematurity (ROP)

Intervention

Drug:
• OHB-607
Participants will receive intravenous infusion of OHB-607 from birth up to PMA 29 weeks + 6 days.

Locations

Country	Name	City	State
Canada	Sainte Justine Hospital	Montreal	Quebec
Canada	Mount Sinai Hospital	Toronto
Finland	Oulun Yliopistollinen Sairaala	Oulu
France	Hôpital Antoine Béclère	Clamart	Hauts-de-Seine
France	Groupe Hospitalier Necker Enfants Malades	Paris
Germany	Universitätsklinikum Freiburg	Freiburg	Baden-Württemberg
Germany	Universitatsklinikum Leipzig	Leipzig	Sachsen
Germany	Klinikum Nürnberg	Nürnberg
Ireland	Cork University Maternity Hospital	Cork	Wilton
Italy	Azienda Ospedaliero-Universitaria Careggi SOD Neonatologia e Terapia Intensiva Neonatale	Firenze
Italy	Istituto Giannina Gaslini-Istituto Pediatrico di Ricovero e	Genova
Italy	Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico	Milano	Lombardia
Italy	Azienda Ospedaliera Di Padova	Padova	Veneto
Italy	Fondazione Policlinico Universitario A Gemelli	Roma	Lazio
Italy	Presidio Ospedaliero Di Treviso Ca' Foncello	Treviso
Japan	Nagano Children's Hospital	Azumino	Nagano
Japan	Osaka Women's and Children's Hospital	Izumi	Ôsaka
Japan	Kagoshima City Hospital	Kagoshima-shi	Kagosima
Japan	Saitama Medical Center	Kawagoe-shi	Saitama
Japan	Kurashiki Central Hospital	Kurashiki-shi	Okayama
Netherlands	Academisch Medisch Centrum Amsterdam	Amsterdam-Zuidoost	Noord-Holland
Netherlands	Maastricht University Medical Center	Maastricht	Limburg
Netherlands	Wilhelmina Children Hospital-University Medical Center Utrecht	Utrecht
Portugal	Hospital Garcia de Orta	Almada
Portugal	Centro Hospitalar Lisboa	Lisboa
Portugal	Maternidade Alfredo da Costa	Lisboa
Portugal	Centro Materno Infantil do Norte - Centro Hospital Universitario do Porto, E.P.E.	Porto
Spain	Hospital General Universitario Dr. Balmis	Alicante
Sweden	Skanes Universitetssjukhus	Lund
Sweden	Karolinska Solna	Stockholm
United Kingdom	University of Cambridge	Cambridge
United Kingdom	Ashford and St. Peter's Hospitals NHS Trust - St. Peter's Hospital	Chertsey	Surrey
United Kingdom	University Hospital Coventry	Coventry
United Kingdom	Liverpool Women's Hospital - PPDS	Liverpool
United Kingdom	Chelsea and Westminster NHS Trust	London
United Kingdom	University College London	London
United Kingdom	St. Mary's Hospital	Manchester
United Kingdom	Norfolk and Norwich University Hospital	Norwich	Norfolk
United States	Boston Children's Hospital	Boston	Massachusetts
United States	Tufts Medical Center	Boston	Massachusetts
United States	Medical University of South Carolina Children Hospital	Charleston	South Carolina
United States	University of Illinois at Chicago	Chicago	Illinois
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Arkansas Children's Hospital	Little Rock	Arkansas
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	LAC USC Medical Center	Los Angeles	California
United States	Jackson Memorial Hospital	Miami	Florida
United States	Ochsner Baptist Medical Center	New Orleans	Louisiana
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Virginia Commonwealth University - Children's Hospital of Richmond at VCU	Richmond	Virginia
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	Tampa General Hospital	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
OHB Neonatology Ltd.

Countries where clinical trial is conducted

United States,  Canada,  Finland,  France,  Germany,  Ireland,  Italy,  Japan,  Netherlands,  Portugal,  Spain,  Sweden,  United Kingdom, 

References & Publications (2)

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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Severe BPD is defined by the modified NICHD severity grading	Baseline through 36 weeks postmenstrual age (PMA)
Secondary	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.	The final weaning off of RTS is defined as the 7th consecutive day that the subject is off RTS.	Baseline through 12 months CA
Secondary	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.	Severe BPD is defined based on the classification according to Jensen et al., 2019	Time Frame: Baseline through 36 weeks postmenstrual age (PMA)
Secondary	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	Severe IVH as classified according to the Volpe criteria	Baseline through 40 weeks postmenstrual age (PMA)
Secondary	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		Baseline through 40 weeks postmenstrual age (PMA)
Secondary	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
Secondary	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
Secondary	Chronic respiratory morbidity outcomes at 24 months CA		24 months CA
Secondary	Incidence and severity of BPD	BPD severity is defined by the modified NICHD severity grading	Baseline through 36 weeks postmenstrual age (PMA)
Secondary	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		36 weeks weeks postmenstrual age (PMA) (± 3 days)
Secondary	Incidence and severity of IVH	Incidence of all grades of IVH as assessed by centrally read CUS and classified according to the Volpe criteria	Baseline through 36 weeks postmenstrual age (PMA)
Secondary	Neurodevelopment outcomes	Neurodevelopmental impairment, Physical and cognitive development will be measured by ASQ®-3 administered at 12 and 24 months CA.	From 6 months CA through 24 months CA
Secondary	Incidence of Retinopathy of Prematurity (ROP)	ROP is classified according to the International Classification	Baseline through 40 weeks PMA
Secondary	Mortality from randomization through to 24 months CA	Mortality rates from randomization to initial hospital discharge and from initial discharge through 24 months CA.	From birth through 24 months CA
Secondary	Exposure-response relationship between measured IGF-1 and Bronchopulmonary Dysplasia (BPD)	Blood samples will be collected to measure IGF-1 and these measured values will be associated with the incidence and severity grade of BPD	Baseline through 36 weeks PMA
Secondary	Exposure-response relationship between measured IGF-1 and intraventricular hemorrhage (IVH)	Blood samples will be collected to measure IGF-1 and these measured values will be associated with the incidence and severity grade of IVH	Baseline through 40 weeks PMA
Secondary	Exposure-response relationship between measured IGF-1 and necrotizing enterocolitis (NEC)	Blood samples will be collected to measure IGF-1 and these measured values will be associated with the incidence and severity grade of NEC	Baseline through 40 weeks PMA
Secondary	Exposure-response relationship between measured IGF-1 and Retinopathy of Prematurity (ROP)	Blood samples will be collected to measure IGF-1 and these measured values will be associated with the incidence and severity grade of ROP	Baseline through 40 weeks PMA
Secondary	To assess the safety profile of OHB-607 as compared to the SNC group.	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.	Baseline through 24 months CA