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
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- The incidence of treatment-emergent adverse events (TEAEs) up to 28 days after receiving MatriPlax
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •A subject has been admitted to an ICU or RCC and is already on or candidates for mechanical ventilation
- •A subject with the primary disease of ARDS caused by documented virus infection (including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2))
- •With normal vital sign parameters:
- •Systolic blood pressure ≥ 90 mmHg and ≤ 160 mmHg
- •Diastolic blood pressure ≥ 50 mmHg and ≤ 95 mmHg
- •Pulse rate ≥ 60 beats per minute (bpm) and ≤ 100 bpm
- •Body temperature ≥ 35.5°C and ≤ 37.7°C
排除标准
- •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)
- •History of pulmonary embolism
- •Previous solid organ transplant
- •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.
- •Presence of any active malignancy within 2 years prior to Screening visit
- •History of the human immunodeficiency virus (HIV) infection
- •History of severe allergic or anaphylactic reactions
- •Known or suspected hypersensitivity or previous adverse reaction to any ingredients of study product
- •Participation in a clinical trial of an interventional medicinal product within 12 weeks prior to Screening visit
- •With any other uncontrolled illness judged by the principal investigator that entering the trial may be detrimental to the subject
- •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)
- •Female subject with childbearing potential who has positive serum or urine pregnancy test at Screening Visit
- •Unable to return for follow-up visits for clinical evaluation or laboratory studies
- •Inappropriate to participate in this clinical study because of psychiatric disorders or any condition as judged by the principal investigator
- •Hypersensitive to penicillin, streptomycin and amphotericin B antibiotics
- •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
- •Use of estrogens/oral contraceptives within 6 weeks prior to Screening visit
- •Current smoker or has smoked within 3 months prior to Screening visit.
研究组 & 干预措施
MatriPlax
Each subject will receive 2x10^7, 4x10^7, or 8x10^7 pcMSCs per administration
干预措施: MatriPlax (Drug)
结局指标
主要结局
The incidence of treatment-emergent adverse events (TEAEs) up to 28 days after receiving MatriPlax
时间窗: 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
时间窗: 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
时间窗: Day 1 to Day 29
SUSAR is an SAE that is considered related to study intervention and unexpected judged by sponsor and investigator
次要结局
- 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)