Umbilical Cord Lining Stem Cells (ULSC) in Patients With COVID-19 ARDS
Study Details
Study Description
Brief Summary
ULSC-CV-01 is a clinical trial that comprises both Phase 1 and Phase 2a, which will be conducted sequentially. This trial will evaluate the safety and potential efficacy of allogeneic Umbilical Cord Lining Stem Cells (ULSC), which are a type of umbilical cord tissue derived mesenchymal stem cells (MSC), with intravenous (IV) administration in hospitalized patients with acute respiratory distress syndrome (ARDS) due to COVID-19.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Detailed Description
The Phase 1, open-label, non-controlled trial in this study will investigate the safety of intravenous (IV) infusion of ULSC in a total of 20 patients with COVID-19-related ARDS that will include patients that are not intubated and not on a ventilator (NV) and patients that are intubated and on a ventilator (V) for respiratory support. Separate cohorts of each group (NV and V) will receive either a single dose (one infusion) or repeat dose (two infusions separated by 48-hour interval).
The Phase 2a randomized and placebo-controlled trial in this study will investigate the potential efficacy of IV infusion of ULSC in a total of 40 patients with COVID-19-related ARDS that will all be EITHER NV or V; the determination of that eligibility criterion and the ULSC dosing regimen will be based on Phase 1 data of safety and tolerability. Phase 2a will evaluate EITHER single dose (one infusion) or repeat dose (two infusions separated by 48-hour interval). The randomization will be 3:1 with 30 patients receiving investigational product (ULSC) and 10 patients receiving placebo (carrier control).
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: ULSC in Phase 1 Open Label Intravenous (IV) infusion of ULSC in 20 patients with COVID-19 ARDS: In Phase 1, two separate cohorts per group will receive either a single dose (one infusion) or repeat dose regimen (two infusions separated by 48-hour interval). The first cohort enrolled will receive the single dose; the next cohort enrolled will be administered the repeat dose regimen. |
Biological: Umbilical Cord Lining Stem Cells (ULSC)
IV infusion of allogeneic ULSC (100 million cells per dose) in sterile saline for injection
Other Names:
|
| Experimental: ULSC in Phase 2a Randomized Intravenous (IV) infusion of ULSC in 30 patients with COVID-19 ARDS: In Phase 2a, 30 patients assigned ULSC will receive either a single dose (one infusion) or repeat dose regimen (two infusions separated by 48-hour interval). The ULSC dosing regimen will be chosen based on Phase 1 data of safety and tolerability. |
Biological: Umbilical Cord Lining Stem Cells (ULSC)
IV infusion of allogeneic ULSC (100 million cells per dose) in sterile saline for injection
Other Names:
|
| Placebo Comparator: Placebo in Phase 2a Randomized Intravenous (IV) infusion of carrier control in 10 patients with COVID-19 ARDS: In Phase 2a, 10 patients assigned Placebo will receive either single dose (one infusion) or repeat dose (two infusions separated by 48-hour interval) of carrier control; the dosing regimen will correspond to that of the experimental arm. |
Other: Placebo (carrier control)
IV infusion of carrier control consisting of sterile saline for injection
|
Outcome Measures
Primary Outcome Measures
- Incidence of Dose Limiting Toxicity (DLT) [24 hours]
Number of subjects with a DLT event during or within 24 hours after ULSC infusion [Dose Limiting Toxicities are treatment-emergent suspected adverse reactions graded as severe, such as severe infusion-related hypersensitivity toxicities of grade ≥3, and any treatment-emergent serious adverse event (SAE) will be investigated to determine if DLT.]
- Incidence of Dose Limiting Toxicity (DLT), suspected adverse reaction (SAR), or serious adverse event (SAE) [1 week]
Number of subjects with a DLT event, suspected adverse reaction, or any serious adverse event (SAE) within 1 week of each ULSC infusion
- Treatment-emergent adverse events (AE) and serious adverse events (SAE) [1 month]
Treatment-emergent adverse events (AE; incidence, grade, and assessment of relatedness or causality) and serious adverse events (SAE) during the study up to 1-month follow-up
- Treatment-emergent adverse events (AE) and serious adverse events (SAE) [12 months]
Treatment-emergent adverse events (AE; incidence, grade, and assessment of relatedness or causality) and serious adverse events (SAE) during the study and up to the 12-month follow-up
Secondary Outcome Measures
- Levels of COVID-19 related ARDS as defined by the Berlin Definition of ARDS [1 month]
Times to transitions between levels of COVID-19 related ARDS as defined by the Berlin Definition of ARDS
- Changes from baseline pulse oximetric saturation SpO2/FiO2 ratio or arterial oxygen pressure pAO2/FiO2 ratio [1 month]
Changes in SpO2/FiO2 ratio or pAO2/FiO2 ratio compared to baseline, measured daily at a minimum; oxygenation index daily when on ventilator
- Number of ventilator-free days (VFD) [1 month]
Number of ventilator-free days (VFD) in period of 1 month from study treatment
- Changes in Complete Blood Count (CBC) with differential from baseline [1 month, 2 months, 3 months, 6 months, and 12 months]
Changes in CBC with differential from baseline to 1 month, 2 months, 3 months, 6 months, and 12 months after study treatment
- Changes in levels of blood glucose (mg/dL) from baseline [1 month, 2 months, 3 months, 6 months, and 12 months]
Changes in blood glucose (mg/dL) from baseline to 1 month, 2 months, 3 months, 6 months, and 12 months after study treatment
- Changes in levels of sodium (mEq/L) from baseline [1 month, 2 months, 3 months, 6 months, and 12 months]
Changes in levels of sodium (mEq/L) from baseline to 1 month, 2 months, 3 months, 6 months, and 12 months after study treatment
- Changes in levels of potassium (mEq/L) from baseline [1 month, 2 months, 3 months, 6 months, and 12 months]
Changes in levels of potassium (mEq/L) from baseline to 1 month, 2 months, 3 months, 6 months, and 12 months after study treatment
- Changes in levels of blood urea nitrogen (BUN; mg/dL) from baseline [1 month, 2 months, 3 months, 6 months, and 12 months]
Changes in levels of blood urea nitrogen (BUN; mg/dL) from baseline to 1 month, 2 months, 3 months, 6 months, and 12 months after study treatment
- Changes in levels of alanine transaminase (ALT; U/L) from baseline [1 month, 2 months, 3 months, 6 months, and 12 months]
Changes in levels of alanine transaminase (ALT; U/L) from baseline to 1 month, 2 months, 3 months, 6 months, and 12 months after study treatment
- Change in Urinalysis (UA) from baseline [1 month]
Change in Urinalysis (UA) at baseline and 1 month after study treatment to assess for presence and qualitative proteinuria
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Adult, male or female, age ≥18 years old
-
Diagnosis of the presence of the COVID-19 agent with confirmation of COVID-19 by standard reverse transcriptase polymerase chain reaction (RT-PCR) or equivalent test.
-
Patient with diagnosis of COVID-related ARDS, classified as either:
-
Not requiring mechanical ventilation (NV) or
-
Requiring mechanical ventilation (V).
According to Berlin Definition of Acute Respiratory Distress Syndrome (ARDS), patients will be categorized based on degrees of hypoxemia [arterial partial pressure of oxygen (PaO2)/oxygen concentration (FiO2)]:
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Mild ARDS: 200 mm Hg < PaO2/FIO2 ≤ 300 mm Hg
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Moderate ARDS: 100 mm Hg < PaO2/FIO2 ≤ 200 mm Hg
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Severe ARDS: PaO2/FIO2 ≤ 100 mm Hg
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Patient who has exhibited deterioration in condition during the past 72 hours prior to the informed consent.
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Patient receiving standard of care in-hospital therapy, including appropriate critical oxygenation, fluid, and hemodynamic support as indicated clinically.
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Patient or responsible family member or surrogate signs informed consent.
Exclusion Criteria
-
Hypersensitivity to study product components. History of hypersensitivity to dimethyl sulfoxide (DMSO).
-
Active cancer or prior diagnosis of cancer within the past year; however, patients with basal and squamous cell cancer of skin will not be excluded.
-
Organ transplant recipient.
-
Chronic renal failure being treated by renal replacement therapy (dialysis) before development of COVID-19.
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Any other condition that, in the judgment of the Investigator or Sponsor, would be a contraindication to enrollment, study product administration, or follow-up.
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Pregnancy or lactation; a negative pregnancy test between screening and day 1 (before administration of treatment) will be required of women with childbearing potential, and they will be advised of the requirement to use an effective means of contraception. A woman is considered to be of childbearing potential unless she is postmenopausal and without menses for 12 months or without a uterus and/or both ovaries.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Miami Baptist Hospital | Miami | Florida | United States | 33176 |
| 2 | Sanford Research | Sioux Falls | South Dakota | United States | 57105 |
Sponsors and Collaborators
- Restem, LLC.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ULSC-CV-01