Acute Respiratory Distress Syndrome, ARDS, COVID-19
Conditions
Brief summary
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.
Interventions
BIOLOGICALHuman umbilical cord mesenchymal stem cells + best supportive care
hUC-MSC product will be administered intravenously in addition to the standard of care treatment.
OTHERPlacebo control + best supportive care
Placebo control will be administered intravenously in addition to the standard of care treatment.
Sponsors
Baylx Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female, aged between 18 and 80; 2. Laboratory (RT-PCR, Gene Sequencing or Antibody) confirmed cases of severe COVID-19 pneumonia with mild to moderate ARDS (Berlin definition); 3. Patients are intubated; 4. Patients who voluntarily adhere to the research procedures and ensure good compliance during the research period; 5. Patients who fully understand the research nature of this study and sign written informed consent.
Exclusion criteria
1. Subjects who have received investigational drug (except for Remdesivir) for the treatment of COVID-19 within 30 days before screening; 2. 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; 3. 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; 4. Subjects receiving extracorporeal membrane oxygenation (ECMO) support. 5. Subjects who are allergic to low-molecular-weight heparin calcium or human albumin; 6. Subjects with ongoing malignant tumors.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of infusion-related adverse events | Day 3 | Safety will be defined by the incidence of infusion-related adverse events as assessed by the treating physician |
| Incidence of any treatment-emergent adverse events (TEAEs) and treatment emergent serious adverse events (TESAEs) | Day 28 | Safety will be defined by the incidence of TEAEs and TESAEs as assessed by the treating physician |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of patients achieving clinical response by the improvement of at least 2 points on the 7-point ordinal scale. | Day 14 | 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. |
| Duration of ICU stay | Day 28 | — |
| Selection of an appropriate dose of BX-U001 for the following Phase 2 study | Day 28 | The dose will be selected based on the assessment of dose-limiting toxicity and maximum tolerated dose. |
| Changes in blood cytokine levels | Day 28 | — |
| Duration of hospital stay | Day 28 | — |
| All-cause mortality | Day 28 | — |
Outcome results
None listed