Back to resultsUmbilical Cord Lining Stem Cells (ULSC) in Patients With COVID-19 ARDS (ULSC)
Primary Purpose
Covid19, Corona Virus Infection, SARS-CoV Infection
Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Umbilical Cord Lining Stem Cells (ULSC)
Placebo (carrier control)
Sponsored by
About this trial
This is an interventional treatment trial for Covid19
Eligibility 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)]:
- Mild ARDS: 200 mm Hg < PaO2/FIO2 ≤ 300 mm Hg
- Moderate ARDS: 100 mm Hg < PaO2/FIO2 ≤ 200 mm Hg
- Severe ARDS: PaO2/FIO2 ≤ 100 mm Hg
- Patient who has exhibited deterioration in condition during the past 72 hours prior to the informed consent.
- Patient receiving standard of care in-hospital therapy, including appropriate critical oxygenation, fluid, and hemodynamic support as indicated clinically.
- 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.
- Any other condition that, in the judgment of the Investigator or Sponsor, would be a contraindication to enrollment, study product administration, or follow-up.
- 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.
Sites / Locations
- Miami Baptist Hospital
- Sanford Research
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
ULSC in Phase 1 Open Label
ULSC in Phase 2a Randomized
Placebo in Phase 2a Randomized
Arm Description
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.
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.
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.
Outcomes
Primary Outcome Measures
Incidence of Dose Limiting Toxicity (DLT)
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)
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)
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)
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
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
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)
Number of ventilator-free days (VFD) in period of 1 month from study treatment
Changes in Complete Blood Count (CBC) with differential from baseline
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
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
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
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
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
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
Change in Urinalysis (UA) at baseline and 1 month after study treatment to assess for presence and qualitative proteinuria
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04494386
Brief Title
Umbilical Cord Lining Stem Cells (ULSC) in Patients With COVID-19 ARDS
Acronym
ULSC
Official Title
Phase 1/2a Study of Umbilical Cord Lining Stem Cells (ULSC) in Patients With ARDS Due to COVID-19
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
July 23, 2020 (Actual)
Primary Completion Date
April 30, 2023 (Anticipated)
Study Completion Date
July 31, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Restem, LLC.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. 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.
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Covid19, Corona Virus Infection, SARS-CoV Infection, ARDS, Coronavirus
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
17 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ULSC in Phase 1 Open Label
Arm Type
Experimental
Arm Description
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.
Arm Title
ULSC in Phase 2a Randomized
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo in Phase 2a Randomized
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Umbilical Cord Lining Stem Cells (ULSC)
Other Intervention Name(s)
Umbilical Cord Lining Stem Cells (ULSC), type of mesenchymal stem cells (MSC) derived from single donor umbilical cord tissue for allogeneic use
Intervention Description
IV infusion of allogeneic ULSC (100 million cells per dose) in sterile saline for injection
Intervention Type
Other
Intervention Name(s)
Placebo (carrier control)
Intervention Description
IV infusion of carrier control consisting of sterile saline for injection
Primary Outcome Measure Information:
Title
Incidence of Dose Limiting Toxicity (DLT)
Description
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.]
Time Frame
24 hours
Title
Incidence of Dose Limiting Toxicity (DLT), suspected adverse reaction (SAR), or serious adverse event (SAE)
Description
Number of subjects with a DLT event, suspected adverse reaction, or any serious adverse event (SAE) within 1 week of each ULSC infusion
Time Frame
1 week
Title
Treatment-emergent adverse events (AE) and serious adverse events (SAE)
Description
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
Time Frame
1 month
Title
Treatment-emergent adverse events (AE) and serious adverse events (SAE)
Description
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
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Levels of COVID-19 related ARDS as defined by the Berlin Definition of ARDS
Description
Times to transitions between levels of COVID-19 related ARDS as defined by the Berlin Definition of ARDS
Time Frame
1 month
Title
Changes from baseline pulse oximetric saturation SpO2/FiO2 ratio or arterial oxygen pressure pAO2/FiO2 ratio
Description
Changes in SpO2/FiO2 ratio or pAO2/FiO2 ratio compared to baseline, measured daily at a minimum; oxygenation index daily when on ventilator
Time Frame
1 month
Title
Number of ventilator-free days (VFD)
Description
Number of ventilator-free days (VFD) in period of 1 month from study treatment
Time Frame
1 month
Title
Changes in Complete Blood Count (CBC) with differential from baseline
Description
Changes in CBC with differential from baseline to 1 month, 2 months, 3 months, 6 months, and 12 months after study treatment
Time Frame
1 month, 2 months, 3 months, 6 months, and 12 months
Title
Changes in levels of blood glucose (mg/dL) from baseline
Description
Changes in blood glucose (mg/dL) from baseline to 1 month, 2 months, 3 months, 6 months, and 12 months after study treatment
Time Frame
1 month, 2 months, 3 months, 6 months, and 12 months
Title
Changes in levels of sodium (mEq/L) from baseline
Description
Changes in levels of sodium (mEq/L) from baseline to 1 month, 2 months, 3 months, 6 months, and 12 months after study treatment
Time Frame
1 month, 2 months, 3 months, 6 months, and 12 months
Title
Changes in levels of potassium (mEq/L) from baseline
Description
Changes in levels of potassium (mEq/L) from baseline to 1 month, 2 months, 3 months, 6 months, and 12 months after study treatment
Time Frame
1 month, 2 months, 3 months, 6 months, and 12 months
Title
Changes in levels of blood urea nitrogen (BUN; mg/dL) from baseline
Description
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
Time Frame
1 month, 2 months, 3 months, 6 months, and 12 months
Title
Changes in levels of alanine transaminase (ALT; U/L) from baseline
Description
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
Time Frame
1 month, 2 months, 3 months, 6 months, and 12 months
Title
Change in Urinalysis (UA) from baseline
Description
Change in Urinalysis (UA) at baseline and 1 month after study treatment to assess for presence and qualitative proteinuria
Time Frame
1 month
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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)]:
Mild ARDS: 200 mm Hg < PaO2/FIO2 ≤ 300 mm Hg
Moderate ARDS: 100 mm Hg < PaO2/FIO2 ≤ 200 mm Hg
Severe ARDS: PaO2/FIO2 ≤ 100 mm Hg
Patient who has exhibited deterioration in condition during the past 72 hours prior to the informed consent.
Patient receiving standard of care in-hospital therapy, including appropriate critical oxygenation, fluid, and hemodynamic support as indicated clinically.
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.
Any other condition that, in the judgment of the Investigator or Sponsor, would be a contraindication to enrollment, study product administration, or follow-up.
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.
Facility Information:
Facility Name
Miami Baptist Hospital
City
Miami
State/Province
Florida
ZIP/Postal Code
33176
Country
United States
Facility Name
Sanford Research
City
Sioux Falls
State/Province
South Dakota
ZIP/Postal Code
57105
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Umbilical Cord Lining Stem Cells (ULSC) in Patients With COVID-19 ARDS
We'll reach out to this number within 24 hrs