Bronchopulmonary Dysplasia, Chronic Lung Disease of Prematurity, Intraventricular Hemorrhage, Retinopathy of Prematurity (ROP)
Conditions
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.
Interventions
DRUGOHB-607
Participants will receive intravenous infusion of OHB-607 from birth up to PMA 29 weeks + 6 days.
Sponsors
OHB Neonatology Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
0 Years to 24 Years
Healthy volunteers
No
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. 9. Birth mother with known HIV or hepatitis (B, C, or E) infection.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 group | Baseline 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 group | Baseline through 40 weeks postmenstrual age (PMA) | — |
| 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 | — |
| 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 | — |
| Chronic respiratory morbidity outcomes at 24 months CA | 24 months CA | — |
| Incidence and severity of BPD | Baseline through 36 weeks postmenstrual age (PMA) | BPD severity is defined by the modified NICHD severity grading |
| 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) | — |
| Incidence and severity of IVH | Baseline 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 |
| Neurodevelopment outcomes | From 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. |
| Incidence of Retinopathy of Prematurity (ROP) | Baseline through 40 weeks PMA | ROP is classified according to the International Classification |
| Mortality from randomization through to 24 months CA | From birth through 24 months CA | Mortality rates from randomization to initial hospital discharge and from initial discharge through 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 |
| 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 |
| 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. |
Countries
Australia, Canada, Finland, Germany, Ireland, Italy, Japan, Netherlands, Portugal, Spain, Sweden, United Kingdom, United States
Outcome results
None listed