Umbilical Cord Lining Stem Cells (ULSC) in Patients With COVID-19 ARDS

NCT04494386 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: ULSC-CV-01
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 2

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.

Conditions

Covid19; Corona Virus Infection; SARS-CoV Infection; ARDS; Coronavirus

Outcome Measures

Primary Outcomes (4)

• Incidence of Dose Limiting Toxicity (DLT)

  Number of subjects with a DLT event during or within 24 hours after ULSC infusion \[Dose Limiting Toxicities are treatment-emergent suspected adverse reactions graded as severe, such as severe infusion-related hypersensitivity toxicities of grade ≥3, and any treatment-emergent serious adverse event (SAE) will be investigated to determine if DLT.\]

  24 hours

• 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

  1 week

• 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

  1 month

• 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

  12 months

Secondary Outcomes (10)

• Levels of COVID-19 related ARDS as defined by the Berlin Definition of ARDS

  1 month

• Changes from baseline pulse oximetric saturation SpO2/FiO2 ratio or arterial oxygen pressure pAO2/FiO2 ratio

  1 month

• Number of ventilator-free days (VFD)

  1 month

• Changes in Complete Blood Count (CBC) with differential from baseline

  1 month, 2 months, 3 months, 6 months, and 12 months

• Changes in levels of blood glucose (mg/dL) from baseline

  1 month, 2 months, 3 months, 6 months, and 12 months

Study Arms (3)

ULSC in Phase 1 Open Label

EXPERIMENTAL

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)

ULSC in Phase 2a Randomized

EXPERIMENTAL

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)

Placebo in Phase 2a Randomized

PLACEBO COMPARATOR

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)

Interventions

Umbilical Cord Lining Stem Cells (ULSC) BIOLOGICAL

IV infusion of allogeneic ULSC (100 million cells per dose) in sterile saline for injection

Also known as: Umbilical Cord Lining Stem Cells (ULSC), type of mesenchymal stem cells (MSC) derived from single donor umbilical cord tissue for allogeneic use

ULSC in Phase 1 Open Label; ULSC in Phase 2a Randomized

Placebo (carrier control) OTHER

IV infusion of carrier control consisting of sterile saline for injection

Placebo in Phase 2a Randomized

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Restem, LLC.: lead

Study Sites (2)

Miami Baptist Hospital

Miami, Florida, 33176, United States

Location

Sanford Research

Sioux Falls, South Dakota, 57105, United States

Location

MeSH Terms

Conditions

COVID-19; Coronavirus Infections; Severe Acute Respiratory Syndrome

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 24, 2020
• First Posted: July 31, 2020
• Study Start: December 23, 2020
• Primary Completion: May 12, 2023
• Study Completion: May 12, 2023
• Last Updated: April 9, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)