Clinical trial NCT04494386: Umbilical Cord Lining Stem Cells (ULSC) in Patients With COVID-19 ARDS
Official title: Phase 1/2a Study of Umbilical Cord Lining Stem Cells (ULSC) in Patients With ARDS Due to COVID-19
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Covid19
Corona Virus Infection
SARS-CoV Infection
ARDS
Coronavirus
Lead sponsor: Restem, LLC.
Sponsor class: INDUSTRY
First posted: 2020-07-31
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Eligibility criteria: Inclusion Criteria:

1. Adult, male or female, age ≥18 years old
2. 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.
3. 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
4. Patient who has exhibited deterioration in condition during the past 72 hours prior to the informed consent.
5. Patient receiving standard of care in-hospital therapy, including appropriate critical oxygenation, fluid, and hemodynamic support as indicated clinically.
6. Patient or responsible family member or surrogate signs informed consent.

Exclusion Criteria

1. Hypersensitivity to study product components. History of hypersensitivity to dimethyl sulfoxide (DMSO).
2. 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.
3. Organ transplant recipient.
4. Chronic renal failure being treated by renal replacement therapy (dialysis) before development of COVID-19.
5. Any other condition that, in the judgment of the Investigator or Sponsor, would be a contraindication to enrollment, study product administration, or follow-up.
6. 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.

Primary outcomes:
measure: Incidence of Dose Limiting Toxicity (DLT)
timeFrame: 24 hours
measure: Incidence of Dose Limiting Toxicity (DLT), suspected adverse reaction (SAR), or serious adverse event (SAE)
timeFrame: 1 week
measure: Treatment-emergent adverse events (AE) and serious adverse events (SAE)
timeFrame: 1 month
measure: Treatment-emergent adverse events (AE) and serious adverse events (SAE)
timeFrame: 12 months
Secondary outcomes:
measure: Levels of COVID-19 related ARDS as defined by the Berlin Definition of ARDS
timeFrame: 1 month
measure: Changes from baseline pulse oximetric saturation SpO2/FiO2 ratio or arterial oxygen pressure pAO2/FiO2 ratio
timeFrame: 1 month
measure: Number of ventilator-free days (VFD)
timeFrame: 1 month
measure: Changes in Complete Blood Count (CBC) with differential from baseline
timeFrame: 1 month, 2 months, 3 months, 6 months, and 12 months
measure: Changes in levels of blood glucose (mg/dL) from baseline
timeFrame: 1 month, 2 months, 3 months, 6 months, and 12 months
measure: Changes in levels of sodium (mEq/L) from baseline
timeFrame: 1 month, 2 months, 3 months, 6 months, and 12 months
measure: Changes in levels of potassium (mEq/L) from baseline
timeFrame: 1 month, 2 months, 3 months, 6 months, and 12 months
measure: Changes in levels of blood urea nitrogen (BUN; mg/dL) from baseline
timeFrame: 1 month, 2 months, 3 months, 6 months, and 12 months
measure: Changes in levels of alanine transaminase (ALT; U/L) from baseline
timeFrame: 1 month, 2 months, 3 months, 6 months, and 12 months
measure: Change in Urinalysis (UA) from baseline
timeFrame: 1 month
Other outcomes:
Locations:
city: Miami
country: United States
facility: Miami Baptist Hospital
state: Florida
city: Sioux Falls
country: United States
facility: Sanford Research
state: South Dakota
Study officials:
References: