Safety and Efficacy of MSC-EVs in the Prevention of BPD in Extremely Preterm Infants

NCT ID: NCT06279741

Last Updated: 2024-09-19

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 265 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-12-28
• Study Completion Date: 2029-12-31

Brief Summary

The phase 1/2 trial aims to evaluate the safety and efficacy of EXOB-001 consisting of extracellular vesicles derived from umbilical cord mesenchymal stromal cells in the prevention of bronchopulmonary dysplasia (BPD) in extremely premature neonates. The study population includes babies born between 23 and 28 (27 + 6 days) weeks of gestational age and body weight between 500g and 1,500 g. Thirty-six subjects will receive one or three administrations of the three doses of EXOB-001 via the endotracheal route in phase 1. In phase 2, two dosages based on the results of phase 1 will be selected and a total of 203 subjects will be randomised to receive either EXOB-001 or placebo (saline solution).

Infants will be followed up to 2 years of corrected age (end of study).

Detailed Description

Bronchopulmonary Dysplasia (BPD) is a chronic severe multifactorial respiratory disease that affects extremely premature infants and is the most common and severe consequence of preterm birth. BPD is associated with disrupted alveolarization and microvascular development, resulting in abnormal gas exchange and lung mechanics. BPD has a multifactorial aetiology, with pre-, peri-, and postnatal mechanisms causing inflammation and injury and resulting in the disruption of the lung's development with the insurgence of an aberrant repair mechanism.

EXOB-001 consists of a population of EVs smaller than 0.22 μm in diameter, containing proteins and nucleic acids, enclosed in a double layer of phospholipids with integral and surface-bound proteins as the main components. EVs exert anti-inflammatory and immunomodulatory activity by reducing the release of proinflammatory cytokines and reducing the recruitment of immune cells in the lung. Current evidence shows that EVs can modulate macrophage phenotype, and this is relevant for BPD, because of the role macrophages have in its pathogenesis.

Two hundred sixty-five (265), 40 in phase 1 (to reach 36 evaluable subjects) + 225 in phase 2 (to reach 203 evaluable subjects), extremely preterm infants at risk of developing BPD with 23 weeks up to 28 (27 weeks+6 days) weeks of gestational age and birth weight between 500g and 1,500g and being endotracheally intubated between postnatal day 3 and day 10 receiving mechanical ventilation with FiO2 > 25%.

Phase 1 will start with cohorts with a single administration starting with a low dose up to a high dose and thereafter start the escalation of cohorts with 3 administrations starting with a low dose up to a high dose. In the case of 3 endotracheal administrations, there will be a window of 24 hours between the administrations (the maximal duration of the treatment with EXOB-001 will be 48 hours).

Phase 2 includes 2 groups with selected dosage levels and regimen of EXOB-001 based on phase 1 interim results. Subjects will be randomised (2:2:1) to receive either EXOB-001 or placebo (saline solution).

Conditions

Bronchopulmonary Dysplasia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

Placebo (Phase 2)

In phase 2, the saline solution for infusion is used as a placebo.

Group Type: PLACEBO_COMPARATOR

Endotracheopulmonary Instillation, Suspension

Intervention Type: BIOLOGICAL

The endotracheal administration can be either by endotracheal tube instillation using a 5 French end-hole catheter or by endotracheal tube instillation using the secondary lumen of a dual lumen endotracheal tube.

The dose is adjusted to body weight and the endotracheal administration will be performed in an already intubated newborn infant.

EXOB-001 (Phase 1)

EXOB-001 will be administered via the endotracheal route in an already intubated newborn. EXOB-001 will be administered in three dose levels (low dose, medium dose and high dose) with one or three administrations.

Group Type: EXPERIMENTAL

Endotracheopulmonary Instillation, Suspension

Intervention Type: BIOLOGICAL

The endotracheal administration can be either by endotracheal tube instillation using a 5 French end-hole catheter or by endotracheal tube instillation using the secondary lumen of a dual lumen endotracheal tube.

The dose is adjusted to body weight and the endotracheal administration will be performed in an already intubated newborn infant.

Active group 1 EXOB-001 (Phase 2)

In phase 2, active group 1 consists of administering the first (out of two) of the safest selected dose/regimen of EXOB-001 based on phase 1 interim results.

Group Type: EXPERIMENTAL

Endotracheopulmonary Instillation, Suspension

Intervention Type: BIOLOGICAL

The endotracheal administration can be either by endotracheal tube instillation using a 5 French end-hole catheter or by endotracheal tube instillation using the secondary lumen of a dual lumen endotracheal tube.

The dose is adjusted to body weight and the endotracheal administration will be performed in an already intubated newborn infant.

Active group 2 EXOB-001 (Phase 2)

In phase 2, active group 2 consists of administering the second (out of two) of the safest selected dose/regimen of EXOB-001 based on phase 1 interim results.

Group Type: EXPERIMENTAL

Endotracheopulmonary Instillation, Suspension

Intervention Type: BIOLOGICAL

The endotracheal administration can be either by endotracheal tube instillation using a 5 French end-hole catheter or by endotracheal tube instillation using the secondary lumen of a dual lumen endotracheal tube.

The dose is adjusted to body weight and the endotracheal administration will be performed in an already intubated newborn infant.

Interventions

Endotracheopulmonary Instillation, Suspension

The endotracheal administration can be either by endotracheal tube instillation using a 5 French end-hole catheter or by endotracheal tube instillation using the secondary lumen of a dual lumen endotracheal tube.

The dose is adjusted to body weight and the endotracheal administration will be performed in an already intubated newborn infant.

Intervention Type: BIOLOGICAL

Other Intervention Names

Endotracheopulmonary instillation

Eligibility Criteria

Inclusion Criteria

• From birth up to 10 days chronological age.
• From 23 weeks up to 28 weeks (27 week+6 days) gestational age at birth.
• Birth weight ≥ 500g but ≤1500g.
• Endotracheally intubated and receiving mechanical ventilation with FiO2 > 25% anytime between 3 and 10 days postnatally or needing re-intubation due to respiratory complications, - Not expected to be extubated within the next 24/48 hours after enrolment.
• Written informed consent from parents/legally designated representative.

Exclusion Criteria

• Surfactant administration less than 24 hours prior to (first) IMP administration.
• Has a congenital heart defect, except for patent ductus arteriosus (PDA), atrial septal defect or a small/moderate, restrictive ventricular septal defect.
• Has a serious malformation of the lung, such as pulmonary hypoplasia/aplasia, congenital diaphragmatic hernia, or any other congenital lung anomaly.
• Being treated with inhaled nitric oxide.
• Has a known chromosomal abnormality (e.g., Trisomy 18, Trisomy 13, or Trisomy 21) or a severe congenital malformation (e.g., hydrocephalus and encephalocele, trachea-oesophageal fistula, abdominal wall defects, and major renal anomalies).
• Has had a known severe congenital infectious disease (i.e., herpes, toxoplasmosis rubella, syphilis, human immunodeficiency virus, cytomegalovirus, etc.).
• Active systemic infection, severe sepsis, or septic shock at Screening up to baseline (phase I) or randomization (phase II).
• Underwent a surgical procedure (requiring admission to an operating room) within 72 hours before baseline (phase I)/randomization (phase II) or who is anticipated to have a surgical procedure (requiring admission to an operating room) within 72 hours before or following baseline (phase I)/randomization (phase II).
• Has had a Grade 3 or 4 intraventricular haemorrhage (IVH).
• Has active pulmonary haemorrhage.
• Has periventricular leukomalacia (PVL).
• The subject is currently participating in any other interventional clinical study.
• The subject is, in the opinion of the Investigator, so ill that death is inevitable, or is considered inappropriate for the study such as an infant that received thoracic compressions and/or adrenaline administration during stabilization in the delivery room and for any reason(s) other than those listed above.

• Maximum Eligible Age: 10 Days
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

EXO Biologics S.A.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Beatrice De Vos, M.D., Ph.D.

Role: STUDY_CHAIR

EXO Biologics SA

Locations

Cliniques Universitaires Saint-Luc (UCLouvain)

Brussels, , Belgium

Site Status: NOT_YET_RECRUITING

ISPPC CHU Charleroi

Charleroi, , Belgium

Site Status: NOT_YET_RECRUITING

Clinique CHC Montlégia

Liège, , Belgium

Site Status: NOT_YET_RECRUITING

AOU Careggi

Florence, , Italy

Site Status: ACTIVE_NOT_RECRUITING

IRCCS Instituto Giannina Gaslini

Genova, , Italy

Site Status: RECRUITING

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, , Italy

Site Status: ACTIVE_NOT_RECRUITING

AOU Policlinico di Modena

Modena, , Italy

Site Status: NOT_YET_RECRUITING

Unità di Fase I della UOC Terapia Intensiva e Patologia Neonatale, Assistenza Neonatale (TINI) dell'Azienda Ospedale Università di Padova

Padua, , Italy

Site Status: RECRUITING

Countries

Belgium; Italy

Central Contacts

Beatrice De Vos, M.D., Ph.D.

Role: CONTACT

b.devos@exobio.be

+32 478 88 26 57

Lorine Preud'homme, M.Sc.

Role: CONTACT

l.preudhomme@exobio.be

+32 468 07 40 71

Facility Contacts

Olivier Danhaive, M.D.

Role: primary

olivier.danhaive@saintluc.uclouvain.be

+32 2 764 79 00

Serge Vanden Eijnden, M.D.

Role: primary

serge.vandeneijnden@chu-charleroi.be

+32 7 192 12 43

Pierre Maton, M.D.

Role: primary

pierre.maton@chc.be

+32 4 355 56 17

Giorgia Brigati, M.D.

Role: primary

giorgiabrigati@gaslini.org

+39 010 56362218

Alberto Berardi, M.D.

Role: primary

alberto.berardi@unimore.it

+39 333 1053301

Eugenio Baraldi, Prof

Role: primary

eugenio.baraldi@unipd.it

+39 049 8213578

Other Identifiers

2022-500293-34

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1291-0283

Identifier Type: OTHER

Identifier Source: secondary_id

EVENEW

Identifier Type: -

Identifier Source: org_study_id