A study evaluating the safety and efficacy of an experimental drug for chronic lung disease against normally prescribed care in extremely premature babies

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Ohb Neonatology Limited

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

5 Jul 2024 → ongoing

Decision date (initial)

2024-10-16

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-515914-41-00

EudraCT number

2018-001393-16

ClinicalTrials.gov

NCT03253263

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Others

To assess the effect of OHB-607 on reducing the burden of CLD, as indicated by a reduction in the incidence of severe BPD (as defined by the modified NICHD severity grading) at 36 weeks (±3 days) PMA, or death at or before 36 weeks PMA, whichever comes first as compared to the SNC group.

Secondary objectives 15

1. To assess the effect of OHB-607 on reducing the burden of CLD, as indicated by a reduction in time to final weaning off of RTS through 12 months CA, as compared to the SNC group.
2. To assess the effect of OHB-607 on reducing the burden of CLD, as indicated by a reduction in the incidence of Grade 2 and Grade 3 (severe) BPD at 36 weeks (±3 days) PMA, or death, whichever comes first as compared to the SNC group, as classified according to Jensen et al., 2019.
3. To assess the effect of OHB-607 on the occurrence of severe (Grade 3 and 4) IVH before 40 weeks PMA, as assessed by CUS as compared to the SNC group.
4. To assess the effect of OHB-607 on occurrence of severe ROP (Stage 3 and above) up to 40 weeks PMA as compared to the SNC group.
5. To assess the effect of OHB-607 on chronic respiratory outcomes as measured by the CLDPSS as compared to the SNC group at 12 months CA.
6. To assess the effect of OHB-607 on neurodevelopment as measured by the Cognitive, Language and Motor Scales of the BSID III as compared to the SNC group at 24 months CA.
7. To assess the effect of OHB-607 on chronic respiratory morbidity outcomes at 24 months CA.
8. To assess the effect of OHB-607 on incidence and severity of BPD.
9. To assess the effect of OHB-607 on Jensen BPD grade at 36 weeks PMA (± 3 days), as classified according to Jensen et al., 2019.
10. To assess the effect of OHB-607 on incidence and severity of IVH.
11. To assess the effect of OHB-607 on other neurodevelopment outcomes.
12. To assess the effect of OHB-607 on incidence and severity of ROP.
13. To assess the effect of OHB-607 on mortality from randomization through 24 months CA.
14. To assess the effect of OHB-607 on exposure-response PK/PD relationships.
15. To assess the safety profile of OHB-607 as compared to the SNC group.

Conditions and MedDRA coding

Chronic Lung Disease

Study design 2 periods

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, European Medicines Agency, Health Canada

EMA paediatric investigation plan (PIP)

EMEA-000534-PIP03-17

Plan to share IPD

No

IPD 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

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. Written informed consents and/or assents must be signed and dated by the subject's parent(s) prior to any study-related procedures. The informed consent and any assents for underage parents must be approved by the Institutional Review Board (IRB)/Independent Ethics Committee (IEC) (in accordance with local regulations).
2. Written informed consents and/or assents must be signed and dated by the subject's birth mother prior to providing study-related information related to birth mother medical history, pregnancy, and the birth of the subject. 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 12

1. Detectable major (or severe) congenital malformation identified before randomization.
2. Isolated minor dysmorphic anomalies that are unlikely to be exclusionary could include post-axial polydactyly, ankyloglossia, accessory nipples, preauricular pits, single or horizontal palmar crease, clinodactyly, and single umbilical artery. However, the presence of multiple minor anomalies in the same infant may be exclusionary.
3. Uncomplicated infantile hemangiomas are unlikely to be exclusionary. However, subjects with infantile hemangiomas that may be associated with potential for disfigurement, life-threatening complications, functional impairment, ulceration, or underlying abnormalities should be excluded.
4. Known or suspected chromosomal abnormality, genetic disorder, or syndrome, identified before randomization, according to the investigator’s opinion.
5. Hypoglycemia at baseline (blood glucose <45 mg/dL or 2.5 mmol/L) which persists in spite of glucose supplementation, to exclude severe congenital abnormalities of glucose metabolism.
6. Clinically significant neurological disease identified before randomization according to cranial ultrasound (CUS) (hemorrhages confined to the germinal matrix are allowed) and investigator’s opinion.
7. Any other condition or therapy that, in the investigator’s opinion, may pose a risk to the subject or interfere with the subject’s potential compliance with this protocol or interfere with interpretation of results.
8. 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).
9. The subject or subject’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.
10. Birth mother with active coronavirus disease 2019 (COVID-19) infection at birth or a history of severe COVID-19 infection (requiring intensive care hospitalization) during pregnancy.
11. Major (or severe) congenital malformations include structurally significant congenital heart disease and structural abnormalities of the upper airway, lungs, or chest wall. Congenital malformations that are suspected of being associated with chromosomal abnormalities, genetic syndromes, and neoplasia should be excluded, as well as abnormalities that may affect life expectancy, cardiopulmonary development, neurologic development, or interpretation of study results.
12. Birth mother with known HIV or hepatitis (B, C, or E) infection.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Incidence of severe BPD (as defined by the modified NICHD severity grading) or death for all subjects at or before 36 weeks (±3 days) PMA.
2. • No BPD: oxygen for <28 days or none • Mild BPD: need for oxygen for ≥28 days but on room air at 36 weeks PMA • Moderate BPD: oxygen for ≥28 days plus treatment with <30% oxygen at 36 weeks PMA • Severe BPD: oxygen for ≥28 days plus oxygen ≥30% and/or any positive pressure ventilation (CPAP, IMV, NNIMV, or high flow nasal cannula ≥2 L/min) at 36 weeks PMA

Secondary endpoints 17

1. Time to final weaning off of RTS from Day 1 of randomization through 12 months CA. The final weaning off of RTS is defined as the 7th consecutive day that the subject is off RTS.
2. Incidence of Grade 2 and Grade 3 (severe) BPD (as per modified Jensen severity grading) or death at 36 weeks PMA. Definitions for BPD are based on Jensen et al., 2019: • No BPD: no support. • Grade 1: nasal cannula ≤2 L/min. • Grade 2: nasal cannula >2 L/min or noninvasive positive airway pressure (CPAP/NIPPV). • Grade 3: invasive mechanical ventilation (IMV).
3. • No BPD: no support • Grade 1: supplemental oxygen <2 L/min without positive pressure (including nasal cannula) • Grade 2: positive pressure support (including CPAP, nasal cannula oxygen ≥2 L/min, NIPPV) • Grade 3: positive pressure ventilation (high-frequency oscillation ventilation and technologies with positive pressure tidal volume breaths, such as IMV
4. Incidence of severe (Grade 3 and 4) IVH before 40 weeks PMA (or NICU discharge/transfer, whichever comes first) as assessed by central blinded reviewers and classified per Volpe criteria (Inder et al., 2018): • Grade 1: blood in germinal matrix with/without IVH <10% of ventricular space. • Grade 2: IVH occupying 10-50% of ventricular space on parasagittal view. • Grade 3: IVH >50% of ventricle or distends ventricle. • Grade 4: periventricular hemorrhagic infarction.
5. Incidence of severe ROP (Stage 3 and above) up to 40 weeks PMA according to International Classification (International Committee for the Classification of Retinopathy of Prematurity, 2021) by local blinded reviewer.
6. Respiratory severity scoring will be determined from information captured during follow-up telephone calls and clinical site visits at intervals specified until 12 months CA using CLDPSS (O’Brodovich et al., 2021).
7. Neurodevelopmental impairment as determined by the separate BSID III scales at 24 months CA. • Motor composite score • Cognitive composite score • Language composite score
8. To be collected through 24 months CA: • Total number of days on RTS in hospital and out of hospital • Number and duration in days of rehospitalizations due to respiratory diagnoses • Number of emergency room visits associated with a respiratory diagnosis • Number of days of respiratory medication use • Respiratory Risk Factors Assessment including breast feeding, vaccines and respiratory syncytial virus prophylaxis, exposure to tobacco, pets, and young children.
9. Incidence of severity of all grades of BPD according to the modified NICHD guidelines for preterm infants born at <32 weeks GA, analyzed separately: none, mild, moderate, and severe BPD.
10. Incidence of all severity grades of BPD as assessed by Jensen et al., 2019: • No BPD: no support • Grade 1: supplemental oxygen <2 L/min without positive pressure (including nasal cannula) • Grade 2: positive pressure support (including CPAP, nasal cannula oxygen ≥2 L/min, NIPPV) • Grade 3: positive pressure ventilation (highfrequency oscillation ventilation and technologies with positive pressure tidal volume breaths, such as IMV)
11. Incidence of all grades of IVH as assessed by centrally read CUS and classified according to the Volpe criteria (Inder et al., 2018).
12. Physical and cognitive development as measured by ASQ-3 administered at 12 and 24 months CA.
13. Incidence and severity of all stages of ROP through 40 weeks PMA according to International Classification (International Committee for the Classification of Retinopathy of Prematurity, 2021) by local blinded reviewer.
14. Mortality rates from randomization to initial hospital discharge and from initial discharge through 24 months CA.
15. Relationships between IGF-1 exposure and respiratory, neurologic, BPD, IVH, NEC, and ROP endpoints.
16. • Incidence, severity & causality of AEs & SAEs • Fatal AEs • Changes from baseline in clinical safety lab parameters (primarily blood glucose), physical examination, and vital signs • IV access status • Central line use • Vision and hearing
17. • Vision and hearing • Concomitant medications or relevant procedures • Development of anti-IGF-1/IGFBP-3 antibodies (IgG and IgM) • Organ hypertrophy (heart, liver, spleen tonsillar, other organ growth) • Incidence of hemangiomas noted during routine clinical assessments

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Ohb Neonatology Limited

Sponsor organisation

Ohb Neonatology Limited

Address

1 Ashley Road

City

Altrincham

Postcode

WA14 2DT

Country

United Kingdom

Scientific contact point

Organisation

Ohb Neonatology Limited

Contact name

Dr. Mark McHale

Public contact point

Organisation

Ohb Neonatology Limited

Contact name

Navdeep Mahajan, M.Sc.

Third parties 8

Locations

7 EU/EEA countries · 18 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Urgent safety measures 1 · Art. 54 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 114 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications