Clinical trial NCT05886985: Safety, Tolerability, and Efficacy of MatriPlax in Subjects With Acute Respiratory Distress Syndrome
Official title: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Acute Respiratory Distress Syndrome
Lead sponsor: BioSpring Medical Co., Ltd
Sponsor class: INDUSTRY
First posted: 2023-06-02
Enrollment: 24
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: MatriPlax
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. 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
2. Administration of study drug must be planned to take place within 72 hours since moderate or severe ARDS diagnosis
3. Either gender, 20 \~ 80 years old (inclusive)
4. Dated and signed informed consent
5. A subject has been admitted to an ICU or RCC and is already on or candidates for mechanical ventilation
6. A subject with the primary disease of ARDS caused by documented virus infection (including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2))
7. With normal vital sign parameters:

   1. Systolic blood pressure ≥ 90 mmHg and ≤ 160 mmHg
   2. Diastolic blood pressure ≥ 50 mmHg and ≤ 95 mmHg
   3. Pulse rate ≥ 60 beats per minute (bpm) and ≤ 100 bpm
   4. Body temperature ≥ 35.5°C and ≤ 37.7°C

Exclusion Criteria:

1. No intent/unwillingness to follow lung-protective ventilation strategy or fluid management manual
2. On extracorporeal membrane oxygenation (ECMO) support
3. Severe chronic respiratory disease with a PaCO2 \> 50 mm Hg or with any oxygen support
4. A subject who is extremely unlikely to survive more than 24 hours in the opinion of the investigator
5. World Health Organization (WHO) Class III or IV pulmonary hypertension
6. Clinical evidence of left ventricular failure
7. 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
8. Severe liver disease (Childs-Pugh Score \> 10)
9. 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)
10. History of pulmonary embolism
11. Previous solid organ transplant
12. With major surgery within 14 days prior to Screening visit Note: Major surgery is defined as an invasive operative procedure where one or more of the following occurred: 1) A body cavity was entered; 2) A mesenchymal barrier was crossed; 3) A fascial plane was opened; 4) An organ was removed; 5) Normal anatomy was operatively altered. All other invasive operative procedures are minor surgeries.
13. Presence of any active malignancy within 2 years prior to Screening visit
14. History of the human immunodeficiency virus (HIV) infection
15. History of severe allergic or anaphylactic reactions
16. Known or suspected hypersensitivity or previous adverse reaction to any ingredients of study product
17. Participation in a clinical trial of an interventional medicinal product within 12 weeks prior to Screening visit
18. With any other uncontrolled illness judged by the principal investigator that entering the trial may be detrimental to the subject
19. Pregnant or lactating or premenopausal with childbearing potential but not taking reliable contraceptive method(s) during the study period. At least one form of birth control must be adopted. Acceptable forms include:

    * Placement of an intrauterine device (IUD) or intrauterine system (IUS).
    * Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps)
20. Female subject with childbearing potential who has positive serum or urine pregnancy test at Screening Visit
21. Unable to return for follow-up visits for clinical evaluation or laboratory studies
22. Inappropriate to participate in this clinical study because of psychiatric disorders or any condition as judged by the principal investigator
23. Hypersensitive to penicillin, streptomycin and amphotericin B antibiotics
24. With specific known risk factors for thrombotic events, including obesity (Body mass index (BMI) \>35), diabetes mellitus Type I, history of deep vein thrombosis (DVT) or thrombotic episodes, acquired or inherited thrombophilic disorders, hypercoagulable conditions, and other cardiovascular risk factors judged by the investigator
25. Use of estrogens/oral contraceptives within 6 weeks prior to Screening visit
26. Current smoker or has smoked within 3 months prior to Screening visit.

Primary outcomes:
measure: The incidence of treatment-emergent adverse events (TEAEs) up to 28 days after receiving MatriPlax
timeFrame: Day 1 to Day 29
measure: The incidence of serious adverse events (SAEs) up to 28 days after receiving MatriPlax
timeFrame: Day 1 to Day 29
measure: The incidence of suspected unexpected serious adverse reactions (SUSAR) up to 28 days after receiving MatriPlax
timeFrame: Day 1 to Day 29
Secondary outcomes:
measure: Changes in PaO2/FiO2 ratio from baseline
timeFrame: Baseline, Day 4, 6, 8, 15, 29
measure: Changes in Lung injury score (LIS) from baseline
timeFrame: Baseline, Day 8, 29
measure: Overall survival
timeFrame: Baseline, Day 29, Month 3, 6, 9, 12
measure: All-cause mortality rate
timeFrame: Baseline, Day 29, Month 3, 6, 9, 12
measure: Cumulative ventilator-free hours (VFH)
timeFrame: Day 1 to 29
measure: Time to the first weaning from ventilator
timeFrame: Up to 12 months
measure: Number of subjects weaned from ventilator
timeFrame: Day 29
measure: Intensive Care Unit (ICU) free hours
timeFrame: Day 1 to 29
measure: Time to the first ICU discharge
timeFrame: Up to 12 months
measure: Number of subjects discharged from ICU
timeFrame: Day 29
measure: ICU/Respiratory Care Center (RCC) free hours
timeFrame: Day 1 to 29
measure: Changes in Sequential Organ Failure Assessment (SOFA) score from baseline
timeFrame: Baseline, Day 4, 6, 8, 15, 29
measure: Cumulative vasopressor free days
timeFrame: Day 1 to 29
measure: Cumulative oxygen support free hours
timeFrame: Day 1 to 29
measure: The net change in c-reactive protein (CRP) from baseline
timeFrame: Baseline, Day 4, 6, 8, 15, and 29
measure: The net change in D-dimer from baseline
timeFrame: Baseline, Day 4, 6, 8, 15, and 29
measure: The net change in Lactate Dehydrogenase (LDH) from baseline
timeFrame: Baseline, Day 4, 6, 8, 15, and 29
measure: The domain scores and total score of 12-item Short Form Survey (SF-12) Quality of Life (QoL) health survey questionnaire
timeFrame: Month 3, 6, 9, 12
measure: Number of subjects who experienced Dose Limiting Toxicity (DLT)
timeFrame: Day 1 to 29
measure: Incidence of TEAEs (treatment-emergent AEs) and SAEs
timeFrame: 12 months
measure: Number of participants with abnormalities in vital signs
timeFrame: Baseline, Day 1, 4, 6, 8, 15, 29, Month 3, 6, 9, 12
measure: Number of participants with abnormalities in physical examination
timeFrame: Baseline, Day 1, 4, 6, 8, 15, 29, Month 3, 6, 9, 12
measure: Number of participants with abnormalities in laboratory examination parameters
timeFrame: Baseline, Day 1, 4, 6, 8, 15, 29
measure: Number of participants with abnormalities in ECG parameters
timeFrame: Baseline, Day 29
Other outcomes:
Locations:
city: Taipei
country: Taiwan
facility: Taipei Medical University Hospital
Study officials:
References:
citation: Chen MC, Lai KS, Chien KL, Teng ST, Lin YR, Chao W, Lee MJ, Wei PL, Huang YH, Kuo HP, Weng CM, Chou CL. pcMSC Modulates Immune Dysregulation in Patients With COVID-19-Induced Refractory Acute Lung Injury. Front Immunol. 2022 Apr 29;13:871828. doi: 10.3389/fimmu.2022.871828. eCollection 2022.