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)
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.
A Phase II Study of Combination Treatment With Extracorporeal Photopheresis and Mesenchymal Stem Cell Infusion for High-Risk and Steroid-Refractory Acute GVHD
The purpose of this study is to see if two treatments (extracorporeal photopheresis and Mesenchymal Stromal Cell (MSC) infusion, can be given safely together, and if they improve the symptoms of a Graft versus Host Disease (GvHD), a complication that can occur in people who undergo stem cell transplant.
Multicenter, Randomized, Dose-search, Parallel, Double-blind, and Placebo-controlled Clinical Trial to Evaluate the Safety and Efficacy of Intramuscular Administration of Allogeneic Adipose Tissue Adult Mesenchymal Stem Cells in Diabetic Patients With Critical Limb Ischemia Without Possibility of Revascularization
Phase II national, multicenter, double-blind, randomized, placebo-controlled, phase-3 clinical trial of 3 parallel groups.
Treatment with allogeneic mesenchymal stromal cells for moderate to severe acute respiratory distress syndrome (START study): a randomised phase 2a safety trial.
1区 · 医学
作者: Michael A Matthay ; Carolyn S Calfee ; Hanjing Zhuo ; B Taylor Thompson ; Jennifer G Wilson ; Joseph E Levitt ; Angela J Rogers ; Jeffrey E Gotts ; Jeanine P Wiener-Kronish ; Ednan K Bajwa ; Michael P Donahoe ; Bryan J McVerry ; Luis A Ortiz ; Matthew Exline ; John W Christman ; Jason Abbott ; Kevin L Delucchi ; Lizette Caballero ; Melanie McMillan ; David H McKenna ; Kathleen D Liu
Treatment with bone-marrow-derived mesenchymal stromal cells (MSCs) has shown benefits in preclinical models of acute respiratory distress syndrome (ARDS). Safety has not been established for administration of MSCs in critically ill patients with ARDS. We did a phase 2a trial to assess safety after administration of MSCs to patients with moderate to severe ARDS.
We did a prospective, double-blind, multicentre, randomised trial to assess treatment with one intravenous dose of MSCs compared with placebo. We recruited ventilated patients with moderate to severe ARDS (ratio of partial pressure of oxygen to fractional inspired oxygen <27 kPa and positive end-expiratory pressure [PEEP] ≥8 cm H2O) in five university medical centres in the USA. Patients were randomly assigned 2:1 to receive either 10 × 106/kg predicted bodyweight MSCs or placebo, according to a computer-generated schedule with a variable block design and stratified by site. We excluded patients younger than 18 years, those with trauma or moderate to severe liver disease, and those who had received cancer treatment in the previous 2 years. The primary endpoint was safety and all analyses were done by intention to treat. We also measured biomarkers in plasma. MSC viability was tested in a post-hoc analysis. This trial is registered with ClinicalTrials.gov, number NCT02097641.
From March 24, 2014, to Feb 9, 2017 we screened 1038 patients, of whom 60 were eligible for and received treatment. No patient experienced any of the predefined MSC-related haemodynamic or respiratory adverse events. One patient in the MSC group died within 24 h of MSC infusion, but death was judged to be probably unrelated. 28-day mortality did not differ between the groups (30% in the MSC group vs 15% in the placebo group, odds ratio 2·4, 95% CI 0·5-15·1). At baseline, the MSC group had numerically higher mean scores than the placebo group for Acute Physiology and Chronic Health Evaluation III (APACHE III; 104 [SD 31] vs 89 ), minute ventilation (11·1 [3·2] vs 9·6 [2·4] L/min), and PEEP (12·4 [3·7] vs 10·8 [2·6] cm H2O). After adjustment for APACHE III score, the hazard ratio for mortality at 28 days was 1·43 (95% CI 0·40-5·12, p=0·58). Viability of MSCs ranged from 36% to 85%.
One dose of intravenous MSCs was safe in patients with moderate to severe ARDS. Larger trials are needed to assess efficacy, and the viability of MSCs must be improved.