AllogeneiC Expanded Human MSC Therapy in Patients Recovering From COVID-19 Acute Respiratory Distress Trial

Study Overview
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Brief Summary
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Allogeneic culture-expanded bone marrow-derived human mesenchymal stem cells (MSC) are the subject of the current study as they are supported by preclinical and clinical data for potential to provide a safe and effective treatment for patients with acute respiratory distress.

Detailed Description
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The majority of Covid-19 cases either are asymptomatic or result in only mild disease. However, in a substantial percentage of patients, a respiratory illness requiring hospital care develops, and such infections can progress to critical illness with hypoxemic respiratory failure requiring prolonged ventilatory support (Zhou 2020) , (Chen 2020) , (Cao 2020) , (Ruan 2020) . Among patients with Covid-19 who have been admitted to hospitals in the United Kingdom, the case fatality rate has been approximately 26%, a percentage that has increased to more than 37% among patients who were undergoing invasive mechanical ventilation.(Docherty 2020) Although remdesivir has been shown to shorten the time until recovery in hospitalized patients, (Beigel 2020). Efforts to modulate inflammation-mediated lung injury and thereby reduce progression to respiratory failure and death have shown promising results. INVESTIGATIONAL PRODUCT The NK1R+ MSC cell therapy are allogeneic bone marrow-derived mesenchymal stem cells that will be delivered intravenously. Details on cell culture and expansion of the cells are provided in the Chemistry Manufacturing and Controls Section of the IND. Cells are provided cryopreserved and are thawed, washed, and prepared for IV delivery. STUDY OBJECTIVES The objective of this clinical trial is to determine the safety and the optimal cell dose of the NK1R+ hMSC in patients recovering from ARDS. .

Official Title
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Phase I/IIa Study to Assess AllogeneiC Expanded Human Mesenchymal Stem Cell Therapy in Patients Recovering From COVID-19 Acute Respiratory Distress Trial (ACE CARD TRIAL)

Conditions
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ARDS, Human

Intervention / Treatment
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* Biological: intravenous delivery of allogeneic bone marrow-derived MSCs


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient > 18 years and ≤ 80 at age at consent Patient must have: Have a laboratory-confirmed COVID-19 diagnosis (nucleic acid-based assay (e.g., RTPCR) to establish the diagnosis of SARS-CoV-2 infection), who recovered from moderate to severe COVID-19 associated ARDS, as determined by Berlin Criteria and been weaned off the ventilator support. Meet the criteria for mild and moderate COVID-19 as described in COVID-19: Developing Drugs and Biological Products for Treatment or Prevention Guidance for Industry (Feb 2021). Recovery from moderate to severe ARDS, diagnosed based on Berlin Criteria, within past 7 days. PaO2/FiO2 > 100 to <200 mmHg with PEEP>5cm H2O Patient or legally authorized representative (LAR) provides written informed consent, except as noted in 21 CFR 50.23 Understands and agrees to comply with planned study procedures Available for clinical follow-up for duration of the treatment and follow-up period Woman of childbearing potential must have a negative pregnancy test at admission or within 24 hours before starting treatment Agree not to become pregnant during treatment and for 1 months after receiving treatment Use at least 2 reliable forms of effective contraception, including 1 barrier method, during treatment and for 1 month after the treatment period Exclusion Criteria: Severe chronic respiratory disease with a PaCO2 > 50 mm Hg or the use of home oxygen (chronic obstructive pulmonary disease or pulmonary fibrosis) Be an organ transplant recipient ALT/AST ≥ 5 times the upper limit of normal BMI > 40 Stage 4 severe kidney disease or requiring dialysis (i.e. eGFR <30) Anticipated transfer to another hospital that is not a study site within 72 hours Shock or on ECMO Pregnant or nursing On a ventilator at the time of enrollment Have received high dose corticosteroids at doses >20 mg per day (or prednisone equivalent) administered for ≥14 consecutive days in the month prior to study entry. Have been diagnosed with cancer Demonstrated inability to comply with the study procedures

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Dose finding study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low dose<br>Experimental: Cohort 1 Low dose, 20M cells, 3 patients | Biological: intravenous delivery of allogeneic bone marrow-derived MSCs<br>* MSCs<br>* Other names: allogeneic NK1R+MSC;|
| Experimental: Medium dose<br>Experimental: Cohort 2 Med dose, 100M cells, 3 patients | Biological: intravenous delivery of allogeneic bone marrow-derived MSCs<br>* MSCs<br>* Other names: allogeneic NK1R+MSC;|
| Experimental: High dose<br>Experimental: Cohort 3 High dose, 200M cells, 3 patients | Biological: intravenous delivery of allogeneic bone marrow-derived MSCs<br>* MSCs<br>* Other names: allogeneic NK1R+MSC;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of product related adverse events through the duration of the study. | Number of product related adverse events through the duration of the study. | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary Endpoint | Number of participants with resolution and/or improvement of ARDS at 7 days, 14 days, 21 days, and 28 days according to the Berlin Criteria. Change in PF ratio from baseline to >200-300, and above >300 Absolute change in PF ratio | 12 months |