Multi-center, Randomized, Placebo Controlled, Interventional Phase 2A Clinical Trial Evaluating the Safety and Potential Efficacy of Multiple Dosing of Mesenchymal Stromal Cells in Patients With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-Cov-2)

2020LS075

This is a multi-center, randomized, placebo controlled, interventional phase 2A trial to evaluate the safety profile and potential efficacy of multi-dosing of mesenchymal stromal cells (MSC) for patients with SARS-CoV-2 associated Acute Respiratory Distress Syndrome (ARDS). After informed consent, treatment assignment will be made by computer-generated randomization to administer either MSC or vehicle placebo control with a 2:1 allocation to the MSC: placebo arm.

2020-07-30

2022-02-25

2023-12-01

Active (not recruiting)

Early phase I

9

Inclusion Criteria: * Age 18-80 years * Meets 'Berlin Criteria' for diagnosis of moderate to severe ARDS for a minimum of 4 hours * Less than 48 hours on a ventilator after meeting criteria for diagnosis of ARDS * SARS-CoV-2 (proven by RT-PCR assay) with radiographic infiltrates * PaO2/FiO2 \< 250 * Positive end-expiratory airway pressure (PEEP) \>5 cm H20 * Elevated C-reactive protein (above laboratory upper limit of normal) * Meets organ function requirements, including left ventricular ejection fraction (LVEF) \>35% ( as defined below) * Off other investigational agents directed against inflammatory cytokines 48 hours prior to enrollment; agents directed against the replication of SARS-CoV-2 \[e.g., Remdesivir\] are permitted * Voluntary informed consent in person or virtually by the patient or patient surrogate considering the face to face limitations during the COVID-19 pandemic and, given the nature of the study population, which frequently requires mechanical ventilation with sedation, surrogate consent will likely occur in a substantial proportion of the study population (this will remain a valid consent until the patient is fully alert, and aware, and can provide a second consent to continue participation in the study). * Adequate organ function is defined as: * Renal: Calculated estimated glomerular filtration rate \>30 mL/min/1.73 m2 (on chemistry panel) * Hepatic: Bilirubin \<3x upper limit of normal (ULN) and AST, ALT and alkaline phosphatase \<5x ULN * Cardiac: Absence of uncontrolled arrhythmia and LVEF \>35% Exclusion Criteria: * Ventilator support of FiO2 \>0·8 or PEEP \>20 cm H2O and ongoing use of more than two vasopressors for 2 or more hours with any agent at doses shown below in the supine position. * Norepinephrine \>12 μg/min or 0.2 μg/kg per min * Phenylephrine \>150 μg/min or 3 μg/kg per min * Epinephrine \>10 ug/min or 0.2 μg/kg per min * Vasopressin \>0.04 units/min * Concurrent use of other investigational agents specifically for treatment of ARDS or inflammatory cytokines. (Note: Agents established to be efficacious and/or those used outside of formal trials are permitted as supportive data emerge) * Known ineligibility for use of a ventilator for a minimum of 7 days, as judged by the institution's Triage Team * Known allergy to MSC components: fetal calf serum, human albumin or DMSO * Active invasive malignant disease requiring chemotherapy/radiation * Other concurrent life-threatening disease (life expectancy \<6 months) or eligible for hospice care * Known history of HIV infection on active treatment * Females who are pregnant or breastfeeding * Current mean arterial pressure (MAP) \<60 mmHg while on 2 or more vasopressors at above doses for more than 2 hours * History of any significant cardiac (myocardial infarction within 12 months of screening visit or unstable angina), chronic ongoing hepatic, or renal disease (grade 3 or higher); diagnosis of congestive heart failure with hypoxemia primarily due to decompensated heart failure; diagnosis of severe chronic obstructive pulmonary disease (COPD) or interstitial lung disease requiring supplemental oxygen at home * Concurrent diagnosis of diffuse alveolar hemorrhage * Requiring continuous dialysis (unable to stop dialysis during study agent infusion)

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'This is a randomized (2:1 ratio) placebo controlled trial.', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'TRIPLE', 'maskingDescription': 'Patients will be randomly assigned (2:1) to receive either 300 × 10\\^6 MSC or vehicle placebo control. Randomization will be stratified by risk (high versus standard risk based on the presence of preexisting co-morbidities), using permuted block sizes of 3. The allocation sequence will be accessed by each cell processing laboratory through ONCORE. Personnel in the cell processing laboratories are not masked to the treatment group, but patients, clinical staff, and investigators will be unaware of treatment assignment. To maintain masking of the investigators and clinicians, bags containing the study products and intravenous tubing had opaque coverings applied in the cell laboratories.', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR']}}, 'enrollmentInfo': {'count': 9, 'type': 'ACTUAL'}}

2023-02-01