A Clinical Efficacy and Safety Study of OHB-607 in Preventing Chronic Lung Disease in Extremely Premature Infants

• ClinicalTrials.gov Identifier: NCT03253263
• Recruitment Status: Active, not recruiting
• First Posted: August 17, 2017
• Last Update Posted: December 12, 2022
• Sponsor: OHB Neonatology Ltd.
• Information provided by (Responsible Party): Oak Hill Bio Ltd ( OHB Neonatology Ltd. )

Tracking Information

• First Submitted Date: August 15, 2017
• First Posted Date: August 17, 2017
• Last Update Posted Date: December 12, 2022
• Actual Study Start Date: May 9, 2019
• Estimated Primary Completion Date: August 28, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 9, 2022)

Reduction in the incidence of severe BPD at 36 weeks (±3 days) PMA, or death, whichever comes first as compared to the SNC group [ Time Frame: Baseline through 36 weeks postmenstrual age (PMA) ]

Severe BPD is defined by the modified NICHD severity grading

Original Primary Outcome Measures (submitted: August 15, 2017)

Incidence of Chronic Respiratory Morbidity (CRM) Through 12 Months Corrected Age (CA) [ Time Frame: Baseline through 12 Months Corrected Age (CA) ]

CRM is a common adverse outcome of premature birth resulting in recurrent respiratory symptoms requiring treatment with pulmonary medications such as bronchodilators, need for supplementary home oxygen, frequent emergency room visits or hospital readmissions, especially during the first year of life. CRM will be measured by respiratory health care utilization and respiratory symptoms.

Current Secondary Outcome Measures (submitted: December 9, 2022)

• Occurrence of severe (Grade 3 and 4) IVH at 36 weeks PMA, as assessed by cranial ultrasound as compared to the SNC group [ Time Frame: Baseline through 36 weeks postmenstrual age (PMA) ]
  Severe IVH as classified according to the Volpe criteria
• Incidence and severity of BPD [ Time Frame: Baseline through 36 weeks postmenstrual age (PMA) ]
  BPD severity is defined by the modified NICHD severity grading
• Incidence and severity of IVH [ Time Frame: Baseline through 36 weeks postmenstrual age (PMA) ]
  IVH grade as classified according to the Volpe criteria
• Neurodevelopment outcomes [ Time Frame: From 6 months CA through 24 months CA ]
  Neurodevelopmental impairment, Physical and cognitive development will be measured by standardised questionnaires
• Incidence of Retinopathy of Prematurity (ROP) [ Time Frame: Baseline through 40 weeks PMA ]
  ROP is classified according to the International Classification
• Mortality from birth through to 24 months CA [ Time Frame: From birth through 24 months CA ]
  Mortality rates from >12 hours after birth through 24 months CA
• Exposure-response Pharmacokinetics/Pharmacodynamics relationships [ Time Frame: Baseline through 40 weeks PMA ]
  Relationship between IGF-1 exposure and study endpoints

Original Secondary Outcome Measures (submitted: August 15, 2017)

• Incidence of Bronchopulmonary Dysplasia (BPD) at Postmenstrual Age (PMA) 36 Weeks [ Time Frame: PMA Week 36 ]
  BPD is a chronic lung disorder characterized by pulmonary immaturity, undifferentiated alveoli with the presence of hyaline membrane and atelectasis, dilated capillaries immersed in the mesenchyme, and a distorted deposition of the extracellular matrix. BPD results in residual effects on pulmonary function and is linked to neurodevelopmental problems during later childhood.
• Incidence of Severe Intraventricular Hemorrhage (IVH) Grade III or IV Through Postmenstrual Age (PMA) 40 Weeks [ Time Frame: Baseline Through PMA 40 Weeks ]
  IVH is characterized by hemorrhage into the germinal matrix tissues of the developing brain. IVH is associated with substantial mortality and morbidity and may result in long-term neurodevelopmental impairments. It has been attributed to changes in cerebral blood flow to the immature germinal matrix microvasculature and secondary periventricular venous infarction. It will be assessed by cerebral ultrasound.
• Incidence of Bronchopulmonary Dysplasia (BPD) at Postmenstrual Age (PMA) 40 Weeks [ Time Frame: PMA Week 40 ]
  BPD is a chronic lung disorder characterized by pulmonary immaturity, undifferentiated alveoli with the presence of hyaline membrane and atelectasis, dilated capillaries immersed in the mesenchyme, and a distorted deposition of the extracellular matrix. BPD results in residual effects on pulmonary function and is linked to neurodevelopmental problems during later childhood.
• Incidence of Chronic Respiratory Morbidity (CRM) or Death Through 6 Months Corrected Age (CA) [ Time Frame: Baseline through 6 Months Corrected Age (CA) ]
  CRM is a common adverse outcome of premature birth resulting in recurrent respiratory symptoms requiring treatment with pulmonary medications such as bronchodilators, need for supplementary home oxygen, frequent emergency room visits or hospital readmissions, especially during the first year of life. CRM will be measured by respiratory health care utilization and respiratory symptoms.
• Functional Status as Assessed by PREMature Infant Index (PREMII) at Postmenstrual Age (PMA) 40 Weeks [ Time Frame: PMA Week 36 ]
  PREMII is a Clinician-Reported Outcome (ClinRO) assessment used to capture overall functional maturation of extremely preterm neonates. Functional Status is defined as what the infant can do with respect to 8 key functional areas (feeding, weight gain, thermoregulation, respiratory support, apnea, bradycardia, desaturation events, and oxygen administration), as a reflection of the infant's overall health and development.
• Incidence of Retinopathy of Prematurity (ROP) [ Time Frame: PMA Week 31 up to Week 40 ]
  The ROP examination will consist of a dilated fundus examination. Typically ROP is classified according to the International Classification (International Committee for the Classification of Retinopathy of Prematurity 2005) and is subdivided into Stage 1 (demarcation line), Stage 2 (ridge), Stage 3 (ridge with extraretinal fibrovascular proliferations), Stage 4 (subtotal retinal detachment), and Stage 5 (total retinal detachment).

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Clinical Efficacy and Safety Study of OHB-607 in Preventing Chronic Lung Disease 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 in Preventing Chronic Lung Disease in Extremely Premature Infants Compared to Standard Neonatal Care
• Brief Summary: The purpose of this study is to determine if an investigational drug can reduce the burden of chronic lung disease in extremely premature infants, as compared to extremely premature infants receiving standard neonatal care alone.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Prevention

Condition

• Bronchopulmonary Dysplasia
• Chronic Lung Disease of Prematurity
• Intraventricular Hemorrhage
• 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.

Other Name: Mecasermin Rinfabate

Study Arms

• Experimental: OHB-607
  Participants will receive continuous IV infusion of OHB-607 through from birth up to PMA 29 weeks +6 days.
  Intervention: Drug: OHB-607
• No Intervention: Standard Neonatal Care
  Standard neonatal care alone will be provided.

• Publications *: 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. 2022 Jun 9. doi: 10.1038/s41390-022-02134-4. Online ahead of print.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: December 9, 2022): 338
• Original Estimated Enrollment (submitted: August 15, 2017): 1053
• Estimated Study Completion Date: November 28, 2026
• Estimated Primary Completion Date: August 28, 2026 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 0 Hours to 24 Hours (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, Finland, France, Germany, Ireland, Italy, Japan, Netherlands, Portugal, Spain, Sweden, United Kingdom, United States
• Removed Location Countries: Israel, Korea, Republic of

Administrative Information

• NCT Number: NCT03253263
• Other Study ID Numbers: OHB-607-202; 2018-001393-16 ( EudraCT Number ); jRCT2071200076 ( Registry Identifier: jRCT )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No
• Plan Description: De-identified individual participant data from this particular study will not be shared in order to minimize the risk that individual patients could be re-identified, given that there are limited numbers of study participants at each study site per year.

• Current Responsible Party: Oak Hill Bio Ltd ( OHB Neonatology Ltd. )
• Original Responsible Party: Shire
• Current Study Sponsor: OHB Neonatology Ltd.
• Original Study Sponsor: Shire
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Oak Hill Bio Ltd
• Verification Date: December 2022