Use of hUC-MSC Product (BX-U001) for the Treatment of COVID-19 With ARDS

Study Overview
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Brief Summary
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This is a phase 1/2a study including 2 parts, phase 1 and phase 2a. The phase 1 part is an open-label, single-arm, dose-escalating study to evaluate the safety and explore the dose limiting toxicity and maximum tolerated dose of a human umbilical cord derived mesenchymal stem cell product (BX-U001) in severe COVID-19 pneumonia patients with acute respiratory distress syndrome (ARDS). Qualified subjects after the screening will be divided into low, medium, or high dose groups to receive a single intravenous infusion of BX-U001 at the dose of 0.5×10^6, 1.0×10^6, or 1.5×10^6 cells/kg of body weight, respectively. The Phase 2a part is a randomized, placebo-controlled, double-blind clinical trial examining the safety and biological effects of BX-U001 at the appropriate dose selected from phase 1 for severe COVID-19 pneumonia patients with the same inclusion/exclusion criteria as the phase 1 part.

Official Title
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A Phase 1/2a Study of the Safety and Efficacy of BX-U001 for the Treatment of Severe COVID-19 Pneumonia With Moderate to Severe Acute Respiratory Distress Syndrome (ARDS).

Conditions
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COVID-19, ARDS, Acute Respiratory Distress Syndrome

Intervention / Treatment
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* Biological: Human umbilical cord mesenchymal stem cells + best supportive care
* Other: Placebo control + best supportive care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, aged between 18 and 80; Laboratory (RT-PCR, Gene Sequencing or Antibody) confirmed cases of severe COVID-19 pneumonia with mild to moderate ARDS (Berlin definition); Patients are intubated; Patients who voluntarily adhere to the research procedures and ensure good compliance during the research period; Patients who fully understand the research nature of this study and sign written informed consent. Exclusion Criteria: Subjects who have received investigational drug (except for Remdesivir) for the treatment of COVID-19 within 30 days before screening; Subjects who are pregnant, breastfeeding or whose urinary pregnancy test is positive before participation in the study; subjects who are pregnant, breastfeeding, have a birth plan, or are unwillingness to use contraception during the study period and within 12 months of infusion; except for subjects who have sterilization surgery or menopause during the study period; Within 3 days before screening/randomization, subjects who have used high-dose corticosteroids that is equivalent to methylprednisolone >240 mg/day or irregular use of systemic corticosteroids to treat other diseases that could affect the efficacy evaluated by the investigator; Subjects receiving extracorporeal membrane oxygenation (ECMO) support. Subjects who are allergic to low-molecular-weight heparin calcium or human albumin; Subjects with ongoing malignant tumors.

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: In phase 1, eligible subjects will be divided into low, medium and high-dose groups with 3 patients/group. If there is no safety concerns for each group, the dose will be escalated from lower dose to the next higher dose. In phase 2a, a total of 30 subjects will be randomized into the treatment and control groups with a ratio of 3:2.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1 Low-dose Group<br>Eligible subjects will receive a single infusion of hUC-MCS product at the dose of 0.5 million cells/kg in addition to standard of care treatment. | Biological: Human umbilical cord mesenchymal stem cells + best supportive care<br>* hUC-MSC product will be administered intravenously in addition to the standard of care treatment.<br>|
| Experimental: Phase 1 Middle-dose Group<br>Eligible subjects will receive a single infusion of hUC-MCS product at the dose of 1 million cells/kg in addition to standard of care treatment. | Biological: Human umbilical cord mesenchymal stem cells + best supportive care<br>* hUC-MSC product will be administered intravenously in addition to the standard of care treatment.<br>|
| Experimental: Phase 1 High-dose Group<br>Eligible subjects will receive a single infusion of hUC-MCS product at the dose of 1.5 million cells/kg in addition to standard of care treatment. | Biological: Human umbilical cord mesenchymal stem cells + best supportive care<br>* hUC-MSC product will be administered intravenously in addition to the standard of care treatment.<br>|
| Experimental: Phase 2a Treatment Group<br>Eligible subjects will receive a single infusion of hUC-MCS product at the selected dose from phase 1 in addition to standard of care treatment. | Biological: Human umbilical cord mesenchymal stem cells + best supportive care<br>* hUC-MSC product will be administered intravenously in addition to the standard of care treatment.<br>|
| Placebo Comparator: Phase 2a Control Group<br>Eligible subjects will receive a single infusion of placebo control and standard of care treatment. | Other: Placebo control + best supportive care<br>* Placebo control will be administered intravenously in addition to the standard of care treatment.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of infusion-related adverse events | Safety will be defined by the incidence of infusion-related adverse events as assessed by the treating physician | Day 3 | 
| Incidence of any treatment-emergent adverse events (TEAEs) and treatment emergent serious adverse events (TESAEs) | Safety will be defined by the incidence of TEAEs and TESAEs as assessed by the treating physician | Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Selection of an appropriate dose of BX-U001 for the following Phase 2 study | The dose will be selected based on the assessment of dose-limiting toxicity and maximum tolerated dose. | Day 28 | 
| All-cause mortality |  | Day 28 | 
| Proportion of patients achieving clinical response by the improvement of at least 2 points on the 7-point ordinal scale. | The scale is as follows: 1. Death 2. Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) 3. Hospitalized, on non-invasive ventilation or high flow oxygen devices 4. Hospitalized, requiring low flow supplemental oxygen 5. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise) 6. Hospitalized, not requiring supplemental oxygen - no longer required ongoing medical care 7. Not hospitalized. | Day 14 | 
| Duration of ICU stay |  | Day 28 | 
| Duration of hospital stay |  | Day 28 | 
| Changes in blood cytokine levels |  | Day 28 |