A Phase I Open-Label, Dose-Escalation Study to Evaluate Safety, Tolerability, and Efficacy of Allogeneic Placenta-derived Human Mesenchymal Stem Cells for the Treatment of Acute Respiratory Distress Syndrome
Overview
- Phase
- Phase 1
- Intervention
- MatriPlax
- Conditions
- Acute Respiratory Distress Syndrome
- Sponsor
- BioSpring Medical Co., Ltd
- Enrollment
- 24
- Locations
- 1
- Primary Endpoint
- The incidence of treatment-emergent adverse events (TEAEs) up to 28 days after receiving MatriPlax
- Status
- Not yet recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
The goal of this clinical trial is to explore the safety, tolerability, and efficacy in study intervention, MatriPlax, in subjects with Acute Respiratory Distress Syndrome (ARDS). MatriPlax contains placenta choriodecidual membrane-derived Mesenchymal Stem Cells (pcMSCs). Participants will receive two doses of MatriPlax on Day 1 and Day 4 and conduct efficacy and safety evaluations until 12 months after treatment or withdrawal from the study.
Detailed Description
This open-label, dose-escalation Phase I study plans to evaluate the safety, tolerability, and efficacy of MatriPlax. This is a conventional 3+3 dose-escalation study in which subjects with moderate or severe ARDS will receive intravenous MatriPlax infusion. Participants will be assigned to one of three dose cohorts (low, middle and high doses of MatriPlax), depending on the time of their enrollment. Each participant will receive two doses of MatriPlax on Day 1 and Day 4. Each dose cohort will have three to six subjects enrolled sequentially with at least 1 week in between. All participants will be followed until 12 months after receiving MatriPlax or withdrawal from the study. A Data Safety and Monitoring Board (DSMB) meeting will be held when all participants of each cohort complete their 28-day of treatment and evaluation period. The DSMB will determine if the study is safe to proceed to the next dose level or it requires to recruit more subjects to the concurrent dose level for safety evaluation.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Clinical diagnosis of moderate or severe ARDS according to the Berlin definition
- •Acute onset of respiratory failure within 1 week of identified insult
- •Respiratory failure associated with known ARDS risk factors and not fully explained by either cardiac failure or fluid overload
- •Radiological abnormalities on chest X-ray or computerized tomography (CT) scan, i.e., bilateral infiltrates that are not fully explained by effusions, lobar/lung collapse, or nodules
- •Hypoxic respiratory failure
- •Moderate ARDS: PaO2/ FiO2 ratio \> 100 mmHg (13.3 kPa) to ≤ 200 mmHg (26.6 kPa) with positive end expiratory pressure (PEEP) ≥ 5 cmH2O
- •Severe ARDS: PaO2/ FiO2 ratio ≤ 100 mmHg (13.3 kPa) with PEEP ≥ 5 cmH2O
- •Administration of study drug must be planned to take place within 72 hours since moderate or severe ARDS diagnosis
- •Either gender, 20 \~ 80 years old (inclusive)
- •Dated and signed informed consent
Exclusion Criteria
- •No intent/unwillingness to follow lung-protective ventilation strategy or fluid management manual
- •On extracorporeal membrane oxygenation (ECMO) support
- •Severe chronic respiratory disease with a PaCO2 \> 50 mm Hg or with any oxygen support
- •A subject who is extremely unlikely to survive more than 24 hours in the opinion of the investigator
- •World Health Organization (WHO) Class III or IV pulmonary hypertension
- •Clinical evidence of left ventricular failure
- •With acute diseases or serious medical conditions include cardiovascular (such as cardiac arrhythmia, QT prolongation), pulmonary (except ARDS), hepatic, neurologic, metabolic, renal, psychiatric condition, autoimmune disease, medical history, physical findings, or laboratory abnormality that in the investigators' opinion are not in stable condition and participating in the study could adversely affect the safety of the subject
- •Severe liver disease (Childs-Pugh Score \> 10)
- •Acute or chronic kidney disease (Stage-3B, 4 or 5 renal impair; estimated glomerular filtration rate (eGFR) ˂ 60 mL/min/1.73 m\^2 or dialysis)
- •Note: eGFR (mL/min/1.73 m\^2) = 186.3 × (serum creatinine in mg/dL)\^-1.154 × (age)\^-0.203× (0.742 if female) × (1.212 if African American/black)
Arms & Interventions
MatriPlax
Each subject will receive 2x10\^7, 4x10\^7, or 8x10\^7 pcMSCs per administration
Intervention: MatriPlax
Outcomes
Primary Outcomes
The incidence of treatment-emergent adverse events (TEAEs) up to 28 days after receiving MatriPlax
Time Frame: Day 1 to Day 29
TEAEs are adverse events (AE) that occur after the study intervention administration
The incidence of serious adverse events (SAEs) up to 28 days after receiving MatriPlax
Time Frame: Day 1 to Day 29
SAE is an AE that results in any of the following outcomes: Death; Life-threatening; Requires inpatient hospitalization or prolongation of existing hospitalization; Results in persistent or significant disability/incapacity; Congenital anomaly/birth defect; Based upon appropriate medical judgment, the event may jeopardize the subject and may require medical or surgical intervention to prevent one of the outcomes listed above
The incidence of suspected unexpected serious adverse reactions (SUSAR) up to 28 days after receiving MatriPlax
Time Frame: Day 1 to Day 29
SUSAR is an SAE that is considered related to study intervention and unexpected judged by sponsor and investigator
Secondary Outcomes
- Overall survival(Baseline, Day 29, Month 3, 6, 9, 12)
- Changes in Sequential Organ Failure Assessment (SOFA) score from baseline(Baseline, Day 4, 6, 8, 15, 29)
- Cumulative vasopressor free days(Day 1 to 29)
- Changes in Lung injury score (LIS) from baseline(Baseline, Day 8, 29)
- Time to the first weaning from ventilator(Up to 12 months)
- The domain scores and total score of 12-item Short Form Survey (SF-12) Quality of Life (QoL) health survey questionnaire(Month 3, 6, 9, 12)
- Number of participants with abnormalities in physical examination(Baseline, Day 1, 4, 6, 8, 15, 29, Month 3, 6, 9, 12)
- Changes in PaO2/FiO2 ratio from baseline(Baseline, Day 4, 6, 8, 15, 29)
- The net change in D-dimer from baseline(Baseline, Day 4, 6, 8, 15, and 29)
- Number of subjects who experienced Dose Limiting Toxicity (DLT)(Day 1 to 29)
- Cumulative ventilator-free hours (VFH)(Day 1 to 29)
- Number of subjects weaned from ventilator(Day 29)
- Time to the first ICU discharge(Up to 12 months)
- The net change in c-reactive protein (CRP) from baseline(Baseline, Day 4, 6, 8, 15, and 29)
- The net change in Lactate Dehydrogenase (LDH) from baseline(Baseline, Day 4, 6, 8, 15, and 29)
- All-cause mortality rate(Baseline, Day 29, Month 3, 6, 9, 12)
- Intensive Care Unit (ICU) free hours(Day 1 to 29)
- Number of subjects discharged from ICU(Day 29)
- ICU/Respiratory Care Center (RCC) free hours(Day 1 to 29)
- Cumulative oxygen support free hours(Day 1 to 29)
- Incidence of TEAEs (treatment-emergent AEs) and SAEs(12 months)
- Number of participants with abnormalities in vital signs(Baseline, Day 1, 4, 6, 8, 15, 29, Month 3, 6, 9, 12)
- Number of participants with abnormalities in laboratory examination parameters(Baseline, Day 1, 4, 6, 8, 15, 29)
- Number of participants with abnormalities in ECG parameters(Baseline, Day 29)