Safety and Tolerability of Allogeneic Umbilical Cord Derived Mesenchymal Stromal Cells (UC-MSCs) to Limit COVID Associated ComplicatioNs: an Open Label, Phase 1 Study in Hospitalized Patients (SAMPSON-1)
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Clinical deterioration
研究概览
简要总结
This is an open-label phase 1 clinical trial of allogeneic umbilical cord derived mesenchymal stromal cells (MSCs) for hospitalized individuals with COVID-19 or other viral pneumonias. Hospitalized individuals who are within 7 days of the onset of a viral pneumonia will be given 2 doses of MSCs at days 1 and 3 after consent. The safety of intravenous infusion will be tested and course of the oxygen response to treatment over 90 days will be evaluated.
详细描述
Study Design: This open-label phase 1 trial in 10 patients will assess the efficacy and safety of UC-MSCs given on day 1 and 3 in hospitalized patients with acute respiratory symptoms between 1 and 7 days after the onset of symptoms.
The following will be assessed in all subjects:
- Age, sex, comorbidities, date of symptoms, source of infection, type of admission, APACHE II score, SOFA score, Clinical status, vital signs including temperature, respiratory rate, oxygen saturation, oxygen requirement, CBC with neutrophil counts, lymphocyte count, CRP, chest imaging (CT or X-ray), location and status in hospital.
- Safety and efficacy: Day 0 (baseline), 3, and 5. Monitoring at 14, 21 and 28 days and monthly for 3 months will be obtained by telephone consult and chart review with serial laboratory.
- Serum or plasma antibody titer to SARS-CoV-2: Day 0, and 5 (additional days 14, 21 and 28 may be included, as available).
- SARS-CoV-2 PCR from nasopharyngeal swabs: Day 0 and 5. (additional day 14, 28 and 60 day samples may be tested if available or at any time when there is clinical suspicion for COVID-19 persistence).
- Outcome measures: O2 requirement (PaO2/FiO2 ratio or SpO2/FIo2), supplemental oxygen strategy (nasal cannula, high flow nasal cannula, noninvasive ventilation, intubation and invasive mechanical ventilation, neuromuscular blocking agent use, prone positioning, corticosteroids, ECMO), vasopressors, renal support, ICU LOS, ICU mortality, Hospital LOS, Hospital mortality, 28 day mortality.
Study Agent:
• Allogeneic UC-MSCs given intravenously at 1.2-1.5 x 106 cells/kg on day 1 and day 3 of study entry. A maximum dose of 100 x 106 cells would be given in each dose. All cellular product will be given with actively growing cells >24 hours from the time of thawing in the Center for Cellular Therapy (CCT) at MUSC. Any emerging FDA guidance will be followed.
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
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Hospitalized with COVID-19 respiratory symptoms and confirmation via COVID-19 SARS-CoV-2 RT-PCR testing.
- •Patient or their surrogate is willing and able to provide written informed consent and comply with all protocol requirements.
- •Diagnosis with Mild or Moderate Pneumonia not requiring mechanical ventilation: Patient must have at least one of the following features:
- •i. Bilateral pneumonia present on chest radiograph or computed tomography ii. Partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2) on arterial blood gas showing: >100mmHg and ≤ 300mmHg regardless of oxygen dose at time of testing.
- •iii. Pulse oxygen saturation (SpO2) at rest ≤ 93% or any degree of hypoxia requiring supplemental oxygen
- •Patient agrees to storage of specimens for future testing.
- •Willingness to undergo mechanical ventilation for worsening
排除标准
- •Intubation with mechanical ventilation prior to study enrolment. High flow nasal cannula and non-invasive mechanical ventilation is allowed.
- •Pneumonia caused by bacteria, mycoplasma, chlamydia, legionella, fungi or other viruses
- •Obstructive pneumonia induced by lung cancer or other known causes
- •Significant comorbid illness likely to impact the outcome of COVID-19 including but not limited to active malignancy other than skin cancer.
- •Patients who are participating in other therapeutic clinical trials within 30 days of consent.
- •History of long-term use of immunosuppressive agents including prednisone dose >5mg daily over the 30 days prior to enrollment.
- •History of severe chronic respiratory disease and requirement for long-term oxygen therapy
- •Undergoing hemodialysis or peritoneal dialysis
- •Estimated or actual rate of creatinine clearance < 15 ml/min
- •History of moderate and severe liver disease (Child-Pugh score >12)
- •Substance abuse sufficient that the patient is unlikely to comply with testing requirements.
- •History of deep venous thrombosis, pulmonary embolism, cerebral vascular disease within the last 3 years
- •Known HIV, hepatitis virus, or syphilis infection
- •Co-Infection of tuberculosis, influenza virus, adenovirus and other respiratory infection virus
- •Moribund patient not expected to survive > 24hours
- •Allergy to diphenhydramine, or hydrocortisone
- •Any condition unsuitable for the study as determined by the investigators
- •Female subjects with positive pregnancy test, breastfeeding, or planning to become pregnant/breastfeed during the study period.
- •Receipt of experimental therapy for COVID-19 with the exception of convalescent plasma, dexamethasone or another corticosteroid, or remdesivir in an open label study.
研究组 & 干预措施
Allogeneic Mesenchymal Stromal Cell infusion
Intravenous infusion of 1.25-1.5 x 10^6 cells/kg with a maximal dose of 100 x 10^6 cells on days 1 and 3 after study enrollment.
干预措施: Allogeneic Mesenchymal Stromal Cells (Biological)
结局指标
主要结局
Clinical deterioration
时间窗: 6 hours
Change in oxygen saturation or clinical symptoms
次要结局
- Hospital mortality and length of stay(90 days)
- Serious Adverse Events(90 days)
- Respiratory support(90 days)
- ICU transfer(90 days)
- 28 day mortality(28 days)
- Ventilator free days(90 Days)