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Bronchopulmonary DysplasiaPhase 1/2EVENEWNCT06279741

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

A Phase 1/2 study testing Endotracheopulmonary Instillation, Suspension in people with Bronchopulmonary Dysplasia, run by EXO Biologics S.A. at 8 sites in 2 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages Up to 10 days
Conditions the study is for
Bronchopulmonary Dysplasia
What is being tested?
Endotracheopulmonary Instillation, Suspension
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
265 participants
Where
8 sitesin 2 countries
Study dates
28 Dec 2023to 31 Dec 2029
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 10 days
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • 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.

Who cannot join

  • 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.).
Show all 13Show fewer
  • 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.

Trial locations and contacts

8 sites in 2 countries. Contact the study team or a site near you to ask about taking part.

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

8 sites in 2 countries

Italy5 sites, 3 recruiting

  • AOU Careggi

    Florence

    Active, not recruiting

  • IRCCS Instituto Giannina Gaslini

    Genova

    Giorgia Brigati, M.D., +39 010 56362218, giorgiabrigati@gaslini.org

    Giorgia Brigati, M.D.

    Recruiting

  • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

    Milan

    Active, not recruiting

  • AOU Policlinico di Modena

    Modena

    Alberto Berardi, M.D., +39 333 1053301, alberto.berardi@unimore.it

    Alberto Berardi, M.D.

    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

    Eugenio Baraldi, Prof, +39 049 8213578, eugenio.baraldi@unipd.it

    Eugenio Baraldi, Prof

    Recruiting

Other trials in Italy

Belgium3 sites, 3 recruiting

  • Cliniques Universitaires Saint-Luc (UCLouvain)

    Brussels, 1200

    Olivier Danhaive, M.D., +32 2 764 79 00, olivier.danhaive@saintluc.uclouvain.be

    Olivier Danhaive, M.D.

    Not yet recruiting

  • ISPPC CHU Charleroi

    Charleroi, 6000

    Serge Vanden Eijnden, M.D., +32 7 192 12 43, serge.vandeneijnden@chu-charleroi.be

    Serge Vanden Eijnden, M.D.

    Not yet recruiting

  • Clinique CHC Montlégia

    Liège, 4000

    Pierre Maton, M.D., +32 4 355 56 17, pierre.maton@chc.be

    Pierre Maton, M.D.

    Not yet recruiting

Other trials in Belgium

About this study

Official title: Phase I Single Arm, Dose Escalating and Phase II Double Blind, Randomized, Placebo-controlled, Dose Finding Clinical Trial Assessing Safety and Efficacy of Intratracheal Administration of Allogeneic Umbilical Cord Mesenchymal Cells-derived Extracellular Vesicles in Preventing Bronchopulmonary Dysplasia in Extremely Preterm Newborns

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).

Read the 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).

Being tested
Endotracheopulmonary Instillation, Suspension
Keywords
EXOB-001, Extracellular vesicles, Bronchopulmonary dysplasia, Extremely premature neonates, Lung inflammation
Medical subject headings
Bronchopulmonary Dysplasia, Pneumonia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Endotracheopulmonary Instillation, SuspensionBiological

    Also called Endotracheopulmonary instillation

    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.

Study groups in NCT06279741
Study groupRoleWhat they receive
EXOB-001 (Phase 1)ExperimentalEXOB-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.
Receives: Biological: Endotracheopulmonary Instillation, Suspension
Active group 1 EXOB-001 (Phase 2)ExperimentalIn 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.
Receives: Biological: Endotracheopulmonary Instillation, Suspension
Active group 2 EXOB-001 (Phase 2)ExperimentalIn 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.
Receives: Biological: Endotracheopulmonary Instillation, Suspension
Placebo (Phase 2)Placebo comparatorIn phase 2, the saline solution for infusion is used as a placebo.
Receives: Biological: Endotracheopulmonary Instillation, Suspension

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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).

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

  2. 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.

    Measured: 36 weeks PMA

Secondary outcomes (10)

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

    The proportion of subjects experiencing treatment-emergent adverse events (TEAE) from EXOB-001 administration up to hospital discharge

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

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

    DLT is measured as:

    • cardiorespiratory decompensation;
    • decrease in SpO2/FiO2 ratio;
    • stable increase in required mean airway pressure >3 cm H2O;
    • death,
    • anaphylactic reaction.
    • any serious adverse reaction (SAR) considered as at least possibly related to EXOB-001 administration.

    Measured: 6 hours and 24 hours after EXOB-001 administration

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

    The number of subjects needing oxygen and ventilation support.

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

  4. Assessment of immune markers (phase 2)

    To test immune markers in the tracheal aspirate fluid.

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

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

    The number of cases and severity of BPD were measured according to different definitions (modified NICHD severity grading (Grade I to IIIA), Jobe and Bancalari 2001, and Isayama 2017).

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

  6. Safety evaluation (phase 1/2)

    All adverse events (AEs) and serious adverse events (SAEs) (including case fatalities), both related and non-related.

    Measured: From enrolment to 2 years of corrected age (end of study)

  7. Assessment of lung ultrasound score (phase 1/2)

    The lung ultrasound score (LUS) aims to assess lung development in all groups by lung ultrasound at different time points.

    Each lung is divided into 3 areas (upper anterior, lower anterior, lateral), and each area will be evaluated by assigning a value ranging from 0 to 3 to each zone, with a consequent overall value ranging between 0 and 18 in all infants scanned on the anterior and later thorax, and also another score (called extended lung ultrasound score or eLUS) in those infants scanned posteriorly ranging between 0 and 30.

    The lung ultrasound scores were assigned as follows:

    • 0, indicates an A-pattern (defined by the presence of the only A-lines);
    • 1, indicates a B-pattern (defined as the presence of ≥3 well-spaced B-lines);
    • 2, indicates severe B pattern (defined as the presence of crowded and coalescent B lines with or without consolidations limited to the subpleural space);
    • 3, indicates extended consolidations.

    Measured: From baseline to 2 years of corrected age (end of study)

  8. Number of subjects with complications of prematurity (phase 1/2)

    To assess all known complications of prematurity, concomitant treatments/procedures/therapies in all groups.

    Measured: From baseline to 2 years of corrected age (end of study)

  9. Assessment of the respiratory morbidity (phase 1/2)

    To evaluate the respiratory morbidity by the Liverpool Respiratory Symptom Questionnaire in all groups at different time points.

    Parents are asked to consider respiratory symptoms over the last 3 months, with questions being scored on a five-point Likert scale from ''not at all'' (score 0) to ''every day'' (score 4). A score for each domain and the complete questionnaire is calculated.

    Measured: From hospital discharge to 2 years of corrected age (end of study)

  10. Assessment of neurodevelopment (phase 1/2)

    To evaluate the neurodevelopmental condition by the ASQ3 questionnaire in all groups with age-specific questionnaires at different time points. The neurodevelopment will be assessed by five domains: communication, gross motor, fine motor, problem-solving, and personal-social.

    Parents will fill out each item and indicate whether the baby is doing the activity regularly (10 points), sometimes (5 points), or not yet (0 points).

    The total score of each developmental area is compared to the area cut-offs.

    Measured: From hospital discharge to 2 years of corrected age (end of study)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Feb 2024
  2. Study start28 Dec 2023
  3. Primary completion31 Jan 2027 (estimated)
  4. Study completion31 Dec 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Model description
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.
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
265 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06279741
Sponsor's protocol ID
EVENEW
Other IDs
2022-500293-34, U1111-1291-0283
Acronym
EVENEW
Status last verified
Sep 2024
First submitted
1 Feb 2024
Last updated
19 Sep 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Endotracheopulmonary Instillation, Suspension in people with Bronchopulmonary Dysplasia, run by EXO Biologics S.A. at 8 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in Italy, Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Beatrice De Vos, M.D., Ph.D. (+32 478 88 26 57, b.devos@exobio.be), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of subjects with treatment-emergent adverse events (phase 1) (time frame: From EXOB-001 administration up to 36 weeks post-menstrual age (PMA)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06279741.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2024.

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