PNEUMOSTEM® for Improving Respiratory Outcomes in Very Premature Infants Diagnosed With Early Pulmonary Arterial Hypertension

Phase 1Not Yet RecruitingNCT07368088

Samsung Medical Center12 enrolled

Overview

The goal of this clinical trial is to evaluate the safety and potential efficacy of PNEUMOSTEM® for improving respiratory outcomes in very premature infants diagnosed with Early Pulmonary Arterial Hypertension. The main questions it aims to answer are: * In very premature infants diagnosed with early pulmonary arterial hypertension, will a single intratracheal administration of PNEUMOSTEM®(Allogeneic umbilical cord blood-derived mesenchymal stem cells) result in improvement of pulmonary arterial hypertension based on echocardiographic assessment? * In very premature infants diagnosed with early pulmonary arterial hypertension who show improvement of pulmonary arterial hypertension based on echocardiographic assessment following a single intratracheal administration of PNEUMOSTEM®(Allogeneic umbilical cord blood-derived mesenchymal stem cells), at what time point does this improvement occur? Participants will: * Single intratracheal dose of PNEUMOSTEM® at 2.0 x 10,000,000 cells/kg * Acute adverse event monitoring: 24 hours post-administration for safety assessment * Follow- up time points: Day 1(Baseline, PNEUMOSTEM® administration), Day 2, Week 1, Week 2, Postnatal Day 28, PMA 36\~40 weeks

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Pulmonary Arterial Hypertension (PAH)Premature Infants

Interventions

PNEUMOSTEM®BIOLOGICAL

PNEUMOSTEM® will be administered intratracheally as a single dose of 2.0x10000000 cells/kg on Day 1.

Eligibility

Sex: ALLMin age: 1 DayMax age: 14 Days

Medical Language ↔ Plain English

Inclusion Criteria: 1. Premature infants within 2 weeks of birth with a gestational age of 28 weeks or less or birth weight of less than 1,250g who require continuous invasive mechanical ventilation 2. When diagnosed with early pulmonary arterial hypertension satisfying condition ① or ② up to 14 days after birth: * When on or more of the following abnormal findings are present on echocardiography performed between 4 and 14 days after birth (findings at 1-3 days after birth correspond to early neonatal transition): 1. Sytemic or suprasystemic pulmonary artery pressure \>40mmHg(based on peak Doppler velocity of tricuspid regurgitation) 2. Right-to-left or bidirectional shunt through patent ductus arteriosus, foramen ovale, or atrial septal defect 3. Flattened interventricular septum or D-shaped left ventricle at end systole ② When receiving nitric oxide(NO) inhalation therapy for persistent pulmonary hypertension of the newborn(PPHN) within 3 days after birth Exclusion Criteria: 1. Those witth cyanotic congenital heart defects or acyanotic congenital heart defects causing heart failure, excluding patent ductus arteriosus in premature infatns 2. Those with severe pulmonary malformations such as congenital diaphragmatic hernia or congenital cystic lung disease 3. Those who underwent surgery within 72 hours before or after administration of the investigational cell product, or those for whom surgery is anticipated 4. Those who received surfactant within 24 hours prior to administration of the investigattional cell product 5. Those with chromosomal abnormalities accompanied by severe malformations(such as Edwards syndrome, Patau syndrome, Down syndrome, etc.) and severe congenital malformations(such as hydrocephalus, encephalocele, etc.) 6. Those with severe congenital infectious diseases(such as herpes, toxoplasmosis, rubella, syphilis, AIDS, etc.) 7. Those with severe sepsis or shock due to active infection not adequately treated with antibiotics 8. Those who have a history of participation in other advanced regenerative medicine clinical studies or clinical trials 9. Others deemed inappropriate by tthe investigator to participate in this advanced regenerative medicine clinical study

Locations (1)

Samsung Medical Center, 81, Irwon-ro, Gangnam-gu, Seoul, Republic of Korea

Seoul, South Korea

Outcomes

Primary Outcomes

Time point(week) of complete reversal of cardiac shunt direction

Time from PNEUMOSTEM administration to complete reversal of intracardiac shunt from right-to-left to complete left-to-right direction, as assessed by echocardiography.

Time frame: Biweekly from day after PNEUMOSTEM administration until postnatal day 28

Time to normalization of ventricular septal configuration

Time from PNEUMOSTEM administration to resolution of flattened interventricular septum or disappearance of D-shaped left ventricle at end-systole, as assessed by echocardiography.

Time frame: Once between postnatal day 28 and PMA 36~40 weeks

Change in duration of pulmonary hypertension medication use

Change in duration of pulmonary hypertension medication use by medication type following PNEUMOSTEM administration compared to standard care. Duration will be measured in days for each medication type used to treat pulmonary hypertension.

Time frame: Daily on PNEUMOSTEM administration day and the next day

Change in duration of mechanical ventilation

Change in total duration of mechalical ventilator use following PNEUMOSTEM andministration compared to standard care. Duration will be measured in days from initiation to discontinuation of mechanical ventilation.

Time frame: Weekly at week 1 and week 2 after PNEUMOSTEM administration

Change in duration of supplemental oxygen therapy.

Change in total duration of supplemental oxygen use following PNEUMOSTEM administration compared to standard care. Duration will be measured in days from initiation to discontinuation of oxygen therapy.

Time frame: Weekly at week 1 and week 2 after PNEUMOSTEM administration

Incidence of Bronchopulmonary Dysplasia(BPD)

Inicidence of bronchopulmonary dysplasia assessed according to standard diagnostic criteria(requirement for supplemental oxygen at 28 days of postnatal age and/or at 36 weeks postmenstrual age).

Time frame: At postnatal day 28 and at between PMA 36~40 weeks

Severity of Bronchopulmonary Dysplasia(BPD)

Severity assessment of bronchopulmonary dysplasia categorized according to the definition of NIHCD 2001, NICHD 2018 and JENSEN 2019.

Time frame: At postnatal day 28 and at between PMA 36~40 weeks

Incidence of Retinopathy of Prematurity(ROP)

Incidence of retinopathy of prematurity assessed by ophthalmologic examination according to the International Classification of Retinopathy of Prematurity.

Time frame: Once at between PMA 36~40 weeks

Severity of Retinopathy of Prematurity(ROP)

Severity assessment of retinopathy of prematurity including staging(Stage 1\~5), zone(Zone I, II, or III), and presence of pulse disease. Assessment of treatment requirements including lase photocoagulation, anti-VEGF injection, or surgical intervention.

Time frame: Once at between PMA 36~40 weeks

Time point of brain injury ditection on Brain MRI

Time point of early detection of brain injury or neurodevelopmental abnormalities on brain MRI performed at postmenstrual age 36\~40 weeks. Brain injuries assessed include intraventricular hemorrhage, periventricular leukomalacia, and other structural abnormalities.

Time frame: Once at between PMA 36~40 weeks

Incidence of Respiratory-related mortality

Incidence of respiratory-related moratlity confirmed by medical records and information survey. Respiratory-related mortality is defined as death primarily attributed to respiratory failure, pulmonary hypertension, or complications of bronchopulmonary dysplasia.

Time frame: From PNEUMOSTEM administration to PMA 36~40 weeks

Tiem point of respiratory-related mortality

Postnatal age(in days) at which respiratory-related death occurs in participants who experience this outcome. Time will be measured from PNEUMOSTEM administration to the date of death.

Time frame: From PNEUMOSTEM administration to PMA 36~40 weeks

Secondary Outcomes

Incidence of Adverse Events Assessed by latest version of CTCAE

Incidence of adverse events graded according to the latest version of Common Terminology Criteria for Adverse Events(CTCAE). All adverse events will be recorded and categorized by system organ class and severity grade.

Time frame: From PNEUMOSTEM administration to PMA 36~40 weeks

Change in anthropometric measurements - Weight

Change in body weight from baseline(PNEUMOSTEM administration day) measured in grams.

Time frame: From PNEUMOSTEM administration to PMA 36~40 weeks

Change in anthropometric measurements - Head Circumference

Change in head circumference from baseline(PNEUMOSTEM administration day) measured in centimeters.

Time frame: From PNEUMOSTEM administration to PMA 36~40 weeks

Abnormal findings on physical examination - Skin and Head/Neck

Incidence of clinically significant abnormal findings on physical examination of skin and head/neck regions.

Time frame: From PNEUMOSTEM administration to PMA 36~40 weeks

Abnormal findings on physical examination - Cardiovascular and Respiratory systems

Incidence of clinically significant abnormal findings on physical examination of heart and lung systems.

Time frame: From PNEUMOSTEM administration to PMA 36~40 weeks

Abnormal findings on physical examination - Abdomen and Genitalia

Incidence of clinically significant abnormal findings on physical examination of abdomen and genitalia.

Time frame: From PNEUMOSTEM administration to PMA 36~40 weeks

Abnormal findings on physical examination - Nervous and Musculoskeletal systems

Incidence of clinically significant abnormal findings on physical examination of nervous system and musculoskeletal systems.

Central Contacts

So Yoon Ahn, M.D, Ph.D

CONTACT

+82-10-4038-0460 yoon.ahn.neo@gmail.com

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Time frame: From PNEUMOSTEM administration to PMA 36~40 weeks

Change in vital signs - Blood pressure

Change in systolic and diastolic blood pressure from baseline(PNEUMOSTEM administration day) measured in mmHg.

Time frame: From PNEUMOSTEM administration to PMA 36~40 weeks

Change in vital signs - Body temperature

Change in body temperature from baseline(PNEUMOSTEM administration day) measured in degrees celsius.

Time frame: From PNEUMOSTEM administration to PMA 36~40 weeks

Change in vital signs - Heart rate

Change in heart rate(pulse) from baseline(PNEUMOSTEM administration day) measured in beats per minute.

Time frame: From PNEUMOSTEM administration to PMA 36~40 weeks

Change in vital signs - Respiratory rate

Change in respiratory rate from baseline(PNEUMOSTEM administration day) measured in breaths per minute.

Time frame: From PNEUMOSTEM administration to PMA 36~40 weeks

Change in vital signs - Oxygen saturation

Change in oxygen saturation(SpO2) from baseline(PNEUMOSTEM administration day) measure as percentage.

Time frame: From PNEUMOSTEM administration to PMA 36~40 weeks

Abnormal laboratory values - Hematology

Incidence of clinically significant abnormal hematology laboratory values including white blood cell count(WBC), red blood cell count(RBC), hemoglobin(Hb), hematocrit(Hct), and platelet count(PLT).

Time frame: Once at screening

Abnormal laboratory values - Blood chemistry

Incidence of clinically significant abnormal blood chemistry values including C-reactive protein(CRP) and other relevant biochemical markers.

Time frame: At screening and within 24 hours after PNEUMOSTEM administration

Abnormal Electrocardiography findings

Incidence of clinically significant abnormal findings on continuous electrocardiography monitoring including arrhythmias, conduction abnormalities, or other cardiac electrical disturbances.

Time frame: From PNEUMOSTEM administration to PMA 36~40 weeks

Incidence of infectious disease

Incidence of infectious disease identified by blood and tracheal aspirate(TTA) cultures with component analysis and pathogen identification.

Time frame: At screening and weekly from baseline(PNEUMOSTEM adminitration day) to week 2

Abnormal blood gas analysis

Incidence of clinically significant abnormal blood gas analysis results for assessment of respiratory and metabolic status including PH, PaO2, PaCO2 and base excess.

Time frame: From PNEUMOSTEM administration to postnatal day 28

Abnormal findings on chest x-ray

Incidence of clinically significant abnormal findings on chest radiography including evaluation for pleural effusion, pneumothorax, infiltrates, or other pulmonary abnormalities.

Time frame: At screening, within 24 hours after PNEUMOSTEM adminitration, a week after PNEUMOSTEM administration, postnatal day 28 and at between PMA 36~40 weeks