MECASERMIN RINFABATE for Bronchopulmonary dysplasia | Chronic lung disease of prematurity

Inclusion criteria

• {"criterion_text":"- 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).\n- 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).\n- Subjects must be between 23 weeks +0 days and 27 weeks +6 days GA, inclusive."}

Exclusion criteria

• {"criterion_text":"- Detectable major (or severe) congenital malformation identified before randomization.\n- 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.\n- 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.\n- Birth mother with known HIV or hepatitis (B, C, or E) infection.\n- 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.\n- 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.\n- Known or suspected chromosomal abnormality, genetic disorder, or syndrome, identified before randomization, according to the investigator’s opinion.\n- 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.\n- Clinically significant neurological disease identified before randomization according to cranial ultrasound (CUS) (hemorrhages confined to the germinal matrix are allowed) and investigator’s opinion.\n- 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.\n- 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).\n- 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."}

Primary endpoints

• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Measured at or before 36 weeks (±3 days) postmenstrual age (PMA); severity defined by modified NICHD severity grading as specified in the protocol."}
• {"endpoint_text":"- • 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","definition_or_measurement_approach":"Defines BPD categories (No, Mild, Moderate, Severe) by oxygen/ventilatory support requirements at 36 weeks PMA, as specified in the modified NICHD severity grading."}

Secondary endpoints

• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Time-to-event measured from randomization Day 1 to the 7th consecutive day off respiratory support (RTS), censored at 12 months corrected age (CA)."}
• {"endpoint_text":"- 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).","definition_or_measurement_approach":"Incidence at 36 weeks PMA using modified Jensen et al. 2019 classification; death prior to assessment is counted."}
• {"endpoint_text":"- • 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","definition_or_measurement_approach":"Alternative representation/definition of BPD severity per Jensen criteria describing support modalities; assessed at 36 weeks PMA."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Cranial ultrasound (CUS) centrally read by blinded reviewers using Volpe criteria; incidence before 40 weeks PMA or NICU discharge/transfer."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Local blinded reviewer assessment up to 40 weeks PMA using International Classification for ROP (2021); incidence of Stage 3+."}
• {"endpoint_text":"- 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).","definition_or_measurement_approach":"CLDPSS score calculated from follow-up telephone calls and site visits at prespecified intervals up to 12 months corrected age."}
• {"endpoint_text":"- Neurodevelopmental impairment as determined by the separate BSID III scales at 24 months CA. • Motor composite score • Cognitive composite score • Language composite score","definition_or_measurement_approach":"Bayley Scales of Infant and Toddler Development (BSID III) composite scores (Motor, Cognitive, Language) assessed at 24 months corrected age."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Collection of healthcare utilisation and exposures through 24 months CA (days on respiratory support, rehospitalisations, ER visits, medication days) and respiratory risk factors assessment."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Incidence by category (none, mild, moderate, severe) per modified NICHD guidelines for infants born <32 weeks GA."}
• {"endpoint_text":"- 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)","definition_or_measurement_approach":"Incidence across Jensen grades assessed at 36 weeks PMA using Jensen et al., 2019 definitions."}
• {"endpoint_text":"- Incidence of all grades of IVH as assessed by centrally read CUS and classified according to the Volpe criteria (Inder et al., 2018).","definition_or_measurement_approach":"Centrally read cranial ultrasound classified by Volpe criteria; incidence of IVH grades through assessment windows."}
• {"endpoint_text":"- Physical and cognitive development as measured by ASQ-3 administered at 12 and 24 months CA.","definition_or_measurement_approach":"Ages & Stages Questionnaire (ASQ-3) administered at 12 and 24 months corrected age to measure physical and cognitive development."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Local blinded reviewer assessment up to 40 weeks PMA using International Classification for ROP (2021); incidence and severity of all stages."}
• {"endpoint_text":"- Mortality rates from randomization to initial hospital discharge and from initial discharge through 24 months CA.","definition_or_measurement_approach":"All-cause mortality measured during hospitalization after randomization and from discharge through 24 months corrected age."}
• {"endpoint_text":"- Relationships between IGF-1 exposure and respiratory, neurologic, BPD, IVH, NEC, and ROP endpoints.","definition_or_measurement_approach":"Exposure-response PK/PD analyses correlating IGF-1 exposure with clinical endpoints (respiratory, neurologic, BPD, IVH, NEC, ROP)."}
• {"endpoint_text":"- • 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","definition_or_measurement_approach":"Standard safety monitoring: incidence/causality of AEs/SAEs, fatal AEs, labs (notably blood glucose), physical exams, vitals, IV access/central line use, vision and hearing assessments."}
• {"endpoint_text":"- • 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","definition_or_measurement_approach":"Additional safety/exploratory endpoints: vision/hearing, concomitant meds/procedures, immunogenicity (anti-IGF-1/IGFBP-3 IgG/IgM), organ hypertrophy monitoring, incidence of hemangiomas during routine assessments."}

Methods

• Antenatal informed consent procedures (documents titled e.g. 'Recruitment Informed Consent Procedure', 'Antenatal Consent Reference Sheet') — channel: in-person antenatal/parent approaches; target audience: birth mothers/parents; country-specific versions available (IT, ES, FI, PT, NL, DE, IE/UK).
• Bassinet stickers and ward posters (K2 Bassinet-Sticker, Parent/Caregiver Posters) — channel: in-hospital physical materials placed in maternity/neonatal units; target audience: new parents and clinical staff; country-specific versions (e.g. IRL EN, DE, FI).
• Brochures, infographics, FAQs and welcome binders (K2 Footprints Brochure, Infographics, ClinicalResearchFAQs, WelcomeBinder) — channel: printed materials handed to parents/caregivers and HCPs; target audience: parents/caregivers and HCPs; country-specific versions available.
• HCP-facing communications and letter templates (K2 Footprints HCP Flyer, HCP Letter Template, Doctor Letter) — channel: professional outreach to clinicians to support identification/referral of eligible subjects; country-specific templates provided.
• ICF videos and e-consent / multimedia ICF materials (L2 ICF Video, ICF Video IRL/DE/PT/NL etc.) — channel: digital multimedia provided to parents to explain study and consent; target audience: parents/birth mothers; country-specific versions.
• eCOA tablet and electronic data collection materials (eCOA-Tablet privacy policy and screenshots) — channel: electronic/remote data capture for follow-up assessments and participant-reported items; supports remote/telephone follow-up assessments.

Italy

Earliest CTIS Part Ii Submission Date

01-10-2024

Latest Decision Or Authorization Date

28-08-2025

Processing Time Days

331

Number Of Sites

5

Number Of Participants

18

Spain

Earliest CTIS Part Ii Submission Date

01-10-2024

Latest Decision Or Authorization Date

10-09-2025

Processing Time Days

344

Number Of Sites

1

Number Of Participants

3

Finland

Earliest CTIS Part Ii Submission Date

01-10-2024

Latest Decision Or Authorization Date

01-09-2025

Processing Time Days

335

Number Of Sites

1

Number Of Participants

3

Portugal

Earliest CTIS Part Ii Submission Date

01-10-2024

Latest Decision Or Authorization Date

28-08-2025

Processing Time Days

331

Number Of Sites

4

Number Of Participants

40

Netherlands

Earliest CTIS Part Ii Submission Date

01-10-2024

Latest Decision Or Authorization Date

08-09-2025

Processing Time Days

342

Number Of Sites

3

Number Of Participants

9

Ireland

Earliest CTIS Part Ii Submission Date

01-10-2024

Latest Decision Or Authorization Date

02-09-2025

Processing Time Days

336

Number Of Sites

1

Number Of Participants

3

Germany

Earliest CTIS Part Ii Submission Date

01-10-2024

Latest Decision Or Authorization Date

28-08-2025

Processing Time Days

331

Number Of Sites

3

Number Of Participants

20

Primary sponsor

Full Name

Ohb Neonatology Limited

Organisation Type

Pharmaceutical company

Country Of Registered Address

United Kingdom

Contract research organisations

Name

PPD Development LP

Responsibilities

Multiple operational and study support functions (e.g., site support, logistics, listed sponsor duties codes and Non-IP supplies); contact EUCTRInquiry.sm@ppd.com

Name

PPD Global Central Labs

Responsibilities

Specimen management and shipment, antibody sampling; contact DL-GCLEU.InvestigatorSupport@ppd.com

Name

Bioclinica Inc.

Responsibilities

Medical imaging services; contact support@bioclinica.com

Name

Yprime LLC

Responsibilities

IVRS / treatment randomisation and related systems; contact ablose@yprimer.com

Third parties

• {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"Multiple sponsor duties codes listed (codes include 1,10,11,12,13,15:Non-IP Supplies,2,5,6,7,8,9) and contact EUCTRInquiry.sm@ppd.com","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Fisher Clinical Services Inc.","duties_or_roles":"Distribution (code 14); contact distribution.allentown@thermofisher.com","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Yprime LLC","duties_or_roles":"IVRS - treatment randomisation (value) and other duties (codes include 15 and 3); contact ablose@yprimer.com","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Belgium","full_name":"PPD Global Central Labs","duties_or_roles":"Specimen management and shipment, antibody sampling (value) and other duties; contact DL-GCLEU.InvestigatorSupport@ppd.com","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"Medical Imaging (value: 'Medical Imaging'); contact support@bioclinica.com","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"PPD Development LP (Richmond address)","duties_or_roles":"Clinical/other support duties (code 4); contact Monica.Agner@ppd.com","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"ePRO system (hardware & software) and related duties; contact customercare@dario.com","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Certara USA Inc.","duties_or_roles":"Modeling / PK/PD support (duties code 4 indicated); contact paul.martin@certara.com","organisation_type":"Pharmaceutical company"}