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

NCT06279741 | Recruiting Phase 1 DMC

• 3 other identifiers: EVENEW2022-500293-34U1111-1291-0283
• Study Type: interventional
• Target: 265
• Locations: 2 countries
• Sites: 8

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).

Conditions

Bronchopulmonary Dysplasia

Keywords

EXOB-001; Extracellular vesicles; Bronchopulmonary dysplasia; Extremely premature neonates; Lung inflammation

Outcome Measures

Primary Outcomes (2)

• Number of subjects with treatment-emergent adverse events (phase 1)

  The proportion of subjects exhibiting acute and short-term safety of the intratracheal administration of EXOB-001 (single dose or multiple doses at different dose levels).

  From EXOB-001 administration up to 36 weeks post-menstrual age (PMA)

• Number of subjects with BPD grade II-III incidence rate per groups (phase 2).

  BPD grade II-III incidence rate per group assessed at 36 weeks PMA. The severity of BPD is assessed according to the modified NICHD severity grading (Grade I to IIIA) definition.

  36 weeks PMA

Secondary Outcomes (10)

• Assessment of medium-term safety of EXOB-001 (phase 1/2)

  From EXOB-001 administration to hospital discharge (between 36 and 40 weeks PMA)

• Number of subjects with dose-limiting toxicity (DLT) (phase 1)

  6 hours and 24 hours after EXOB-001 administration

• Number of subjects needing for oxygen and ventilation for BPD incidence (phase 1/2)

  28 days chronological age, 36 weeks PMA, 40 weeks PMA

• Assessment of immune markers (phase 2)

  Baseline (before EXOB-001 administration), baseline + 24 hours before EXOB-001 administration, baseline + 72 hours if the the subject is still intubated

• Assessment of BPD incidence and severity (phase 1/2)

  28 days of chronological age, 36 weeks PMA and 40 weeks PMA

Study Arms (4)

EXOB-001 (Phase 1)

EXPERIMENTAL

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.

Biological: Endotracheopulmonary Instillation, Suspension

Active group 1 EXOB-001 (Phase 2)

EXPERIMENTAL

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.

Biological: Endotracheopulmonary Instillation, Suspension

Active group 2 EXOB-001 (Phase 2)

EXPERIMENTAL

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.

Biological: Endotracheopulmonary Instillation, Suspension

Placebo (Phase 2)

PLACEBO COMPARATOR

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

Biological: Endotracheopulmonary Instillation, Suspension

Interventions

Endotracheopulmonary Instillation, Suspension 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.

Also known as: Endotracheopulmonary instillation

Active group 1 EXOB-001 (Phase 2); Active group 2 EXOB-001 (Phase 2); EXOB-001 (Phase 1); Placebo (Phase 2)

Eligibility Criteria

• Age: Up to 10 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• EXO Biologics S.A.: lead

Study Sites (8)

Cliniques Universitaires Saint-Luc (UCLouvain)

Brussels, 1200, Belgium

NOT YET RECRUITING

ISPPC CHU Charleroi

Charleroi, 6000, Belgium

NOT YET RECRUITING

Clinique CHC Montlégia

Liège, 4000, Belgium

NOT YET RECRUITING

AOU Careggi

Florence, Italy

ACTIVE NOT RECRUITING

IRCCS Instituto Giannina Gaslini

Genova, Italy

RECRUITING

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, Italy

ACTIVE NOT RECRUITING

AOU Policlinico di Modena

Modena, Italy

NOT YET RECRUITING

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

Padua, 35128, Italy

RECRUITING

MeSH Terms

Conditions

Bronchopulmonary Dysplasia; Pneumonia

Interventions

Suspensions

Condition Hierarchy (Ancestors)

Ventilator-Induced Lung Injury; Lung Injury; Lung Diseases; Respiratory Tract Diseases; Infant, Premature, Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Respiratory Tract Infections; Infections

Intervention Hierarchy (Ancestors)

Colloids; Complex Mixtures; Dosage Forms; Pharmaceutical Preparations

Study Officials

• Beatrice De Vos, M.D., Ph.D.

  EXO Biologics SA

  STUDY CHAIR

Central Study Contacts

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

CONTACT

+32 478 88 26 57; b.devos@exobio.be

Lorine Preud'homme, M.Sc.

CONTACT

+32 468 07 40 71; l.preudhomme@exobio.be

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Phase 1 is an open-label, dose-escalation and single-arm study. In phase 2, Investigators will remain blinded to each subject's assigned treatment throughout the study. The Sponsor will put in place procedures to maintain this blind. Indeed, to ensure the blinding of the groups, the preparation and administration of the test product will be organized by different teams. In the event of a Quality Assurance audit, the auditor(s) will be allowed access to unblinded study treatment records at the site(s) to verify that randomisation/dispensing has been done accurately. Blinding will be broken by the Investigator for emergency purposes only, where knowledge of the blinded treatment could influence further subject care. In addition, subjects will be unblinded for safety reports, as per regulatory requirements. Study blind will be broken after the database lock.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase 1 is an open-labelled, dose-escalated, and single-arm of EXOB-001. Phase 2 is a randomised, double-blind, placebo-controlled, and dose-finding of EXOB-001.

Study Record Dates

• First Submitted: February 1, 2024
• First Posted: February 28, 2024
• Study Start: December 28, 2023
• Primary Completion (Estimated): January 31, 2027
• Study Completion (Estimated): December 31, 2029
• Last Updated: September 19, 2024

Record last verified: 2024-09

Locations

BE (3); IT (5)