hCT-MSCs for COVID19 ARDS
hCT-MSCs for COVID19 ARDS
This is a 30 patient, Phase 1/2a multi-center pilot study to test the safety and to describe
 the preliminary efficacy of intravenous administration of allogenic human cord tissue
 mesenchymal stromal cells (hCT-MSC) as an investigational agent, under U.S. IND 19968 to
 patients with acute respiratory distress syndrome (ARDS) due to COVID-19 infection
 (COVID-ARDS). The key secondary endpoints are 28 day survival, an increase in PaO2/FiO2 ratio
 by 50% at 96 hours, days to hospital discharge to home or rehab, and number of days requiring
 mechanical ventilation.

 Patients will be eligible for treatment with 3 daily consecutive doses of hCT-MSC at 1
 million cells/kg (max dose 100 million cells), 18-30 hours apart, if they have a confirmed
 diagnosis of COVID-19 and meet clinical and radiographic criteria for ARDS.

 Results from the first 10 patients will be compared with concurrent outcomes utilizing
 standard of care treatments in participating hospitals and in published reports in the
 medical literature. Results from the additional 20 patients will be combined with the first
 10 and analyzed. The trial is relying on focused eligibility of the participants (patients
 with ARDS), single cohort with short trial time (4 weeks), and simple assessment of clinical
 outcome (survival, improvement of ARDS). This is a sequential design in the sense that after
 the first 10 patients are evaluated a decision will be made by the PIs and the Data Safety
 Monitoring Board whether to proceed with the exploratory randomized portion of the study.
Inclusion Criteria:

 1. The patient or legally authorized representative (LAR) must have the ability to
 understand and the willingness to provide a signed and dated informed consent form.

 2. Age 18 years and over

 3. The patient agrees to use adequate contraception for the duration of the treatment
 protocol and for 6 months post treatment.

 4. Positive RT- PCR testing for COVID-19 nucleic acid using nasopharyngeal swabbing or
 any other site

 5. Patient meets ARDS criteria as defined by Berlin criteria, and is on mechanical
 ventilation a. Berlin criteria for ARDS are: i. bilateral opacities on chest imaging
 consistent with pulmonary edema ii. A need for positive pressure ventilation via
 endotracheal or tracheostomy tube iii. PaO2/FiO2 ratio ≤ 300mmHg with a minimum of 5
 cmH20 PEEP iv. Infiltrates not fully explained by cardiac failure or fluid overload in
 the physician's best clinical judgement ARDS onset is considered the time that the
 last of criteria 1-4 is met. Infiltrates considered "consistent with pulmonary edema"
 include any infiltrate not due to mass, atelectasis, or effusion, or opacities known
 to be chronic (greater than 1 week old). Vascular redistribution or indistinct vessels
 or heart border alone do not qualify as opacities.

 Exclusion Criteria:

 1. Evidence of multiorgan failure involving one or more organs, excluding the lungs as
 defined below:

 1. Presence of shock, defined as MAP < 65 mmHg with signs of peripheral
 hypoperfusion, or continuous infusion of 2 or more vasopressor or inotrope agents
 to maintain MAP ≥ 65 mmHg.

 2. Serum bilirubin > 10 mg/dl

 3. Platelet count < 50,000/ml

 2. Evidence of acquired or congenital immunodeficiency (due to immunosuppressive therapy,
 HIV, previous treatment for cancer, etc.)

 3. History of metastatic cancer in the past 3 years

 4. History of previous treatments with MSCs or other cell therapies

 5. Patient is co-enrolled in any other IND-sponsored clinical trials for COVID-19

 6. Evidence of pregnancy or lactation

 7. Moribund patient not expected to survive > 24 hours

 8. Unable/unwilling to deliver lung protective ventilation

 9. Patient is receiving Extracorporeal Membrane Oxygenation (ECMO)