Use of UC-MSCs for COVID-19 Patients

NCT04355728 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: 2020067120200370
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study is to learn about the safety and efficacy of human umbilical cord derived Mesenchymal Stem Cells (UC-MSC) for treatment of COVID-19 Patients with Severe Complications of Acute Lung Injury/Acute Respiratory Distress Syndrome (ALI/ARDS).

Conditions

Corona Virus Infection; ARDS; ARDS, Human; Acute Respiratory Distress Syndrome; COVID-19

Keywords

COVID-19

Outcome Measures

Primary Outcomes (8)

• Number of Participants With Pre-Specified Infusion Associated Adverse Events

  Safety as defined by the number of pre-specified infusion associated adverse events as assessed by treating physician. Any of the following occurring within 6 h post each infusion: 1. An increase in vasopressor dose greater than or equal to the following: * Norepinephrine: 10 μg/min * Phenylephrine: 100 μg/min * Dopamine: 10 μg/kg/min * Epinephrine: 10 μg/min 2. In patients receiving mechanical ventilation: worsening hypoxemia, as assessed by a requirement for an increase of PEEP by 5 cm H2O over baseline, or requirement to increase FiO2 of \>20%. 3. In patients receiving high flow oxygen therapy: worsening hypoxemia, as indicated by requirement of intubation and mechanical ventilation. 4. New cardiac arrhythmia requiring cardioversion 5. New ventricular tachycardia, ventricular fibrillation, or asystole 6. A clinical scenario consistent with transfusion incompatibility or transfusion-related infection 7. Cardiac arrest or death within 24h post infusion

  6 and 24 hours

• Number of Subjects With Serious Adverse Events by 31 Days After First Infusion

  The number of subjects experiencing serious adverse events by 31 days after the first infusion (corresponding to 28 days after the last infusion).

  31 days

• Percentage of Participants Experiencing Serious Adverse Events (SAEs) Through Study Day 90

  Safety will be reported as the percentage of participants experiencing serious adverse events through Day 90 as assessed by treating physician.

  90 days

• Number of Adverse Events (AEs) and Serious Adverse Events (SAEs)

  Total number of adverse events and serious adverse events as assessed by treating physician

  90 days

• Number of Adverse Events (AEs) and Serious Adverse Events (SAEs) by Severity

  Total number of adverse events plus serious adverse events categorized by severity.

  90 days

• Subjects With Adverse Events and Serious Adverse Events by Severity

  Total number of subjects with adverse events and serious adverse events categorized by severity.

  90 days

• Number of Adverse Events and Serious Adverse Events by Relatedness to Treatment

  Total number of adverse events and serious adverse events categorized by relatedness to treatment defined by a medical professional.

  90 days

• Subjects With Adverse Events by Relatedness to Treatment

  Total number of subjects with adverse events categorized by relatedness to treatment by a medical professional

  90 days

Secondary Outcomes (43)

• Survival at 31 Days Post First Infusion

  31 Days

• Survival at 60 Days Post First Infusion

  60 days

• Time to Recovery

  31 days

• Ventilator-Free Days Throughout 28 Days Post Second Infusion

  28 days post second infusion

• Ventilator-Free Days Throughout 90 Days

  90 days or hospital discharge, whichever is earlier

Study Arms (2)

UC-MSCs Group

EXPERIMENTAL

Participants in this group will be treated with two infusions of UC-MCSs along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment.

Biological: Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care.

Control Group

PLACEBO COMPARATOR

Participants in this group will be treated with two infusions of vehicle along with heparin (blood thinner) in addition to standard of care treatment. The first infusion will be administered within 24 hours of study enrollment and the second infusion will be administered within 72 hours of study enrollment.

Other: Vehicle + Heparin along with best supportive care

Interventions

Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care. BIOLOGICAL

UC-MSC will be administered at 100x10\^6 cells/infusion administered intravenously in addition to the standard of care treatment.

UC-MSCs Group

Vehicle + Heparin along with best supportive care OTHER

Best supportive care treatment per the treating hospital protocol.

Control Group

Eligibility Criteria

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

You may qualify if:

• Patient currently hospitalized
• Aged ≥ 18 years
• Willing and able to provide written informed consent, or with a legal representative who can provide informed consent
• Peripheral capillary oxygen saturation (SpO2) ≤ 94% at room air, or requiring supplemental oxygen at screening
• PaO2/FiO2 ratio \< 300 mmHg
• Bilateral infiltrates on frontal chest radiograph or bilateral ground glass opacities on a chest CT scan
• Hypoxemia requiring an increase in the fraction of inspired oxygen (FiO2) of ≥ 20% AND an increase in positive end-expiratory airway pressure (PEEP) level of 5 cm H2O or more to maintain transcutaneous oxygen saturations in the target range of 88-95%, or requirement for escalation from oxygen therapy to invasive mechanical ventilation

You may not qualify if:

• PaO2/FiO2 ≥ 300 at the time of enrollment
• A previous MSC infusion not related to this trial
• History of Pulmonary Hypertension (WHO Class III/IV)
• History of left atrial hypertension or decompensated left heart failure.
• Pregnant or lactating patient
• Unstable arrhythmia
• Patients with previous lung transplant
• Patients currently receiving chronic dialysis
• Patients currently receiving Extracorporeal Membrane Oxygenation (ECMO)
• Presence of any active malignancy (except non-melanoma skin cancer)
• Any other irreversible disease or condition for which 6-month mortality is estimated to be greater than 50%
• Moderate to severe liver disease (AST and ALT \>5 X ULN)
• Severe chronic respiratory disease with a PaCO2 \> 50 mm Hg or the use of home oxygen
• Baseline QT prolongation
• Moribund patient not expected to survive \> 24 hours

Sponsors & Collaborators

• Camillo Ricordi: lead

Study Sites (1)

Diabetes Research Institute, University of Miami Miller School of Medicine

Miami, Florida, 33136, United States

Location

MeSH Terms

Conditions

Coronavirus Infections; Respiratory Distress Syndrome; COVID-19

Condition Hierarchy (Ancestors)

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

Limitations and Caveats

The inferences we make from the efficacy results observed in this phase 1/2a trial in 24 subjects, including the outcome of survival, are still subject to limitations of sample size and potential bias because of factors we were not yet aware of.

Results Point of Contact

• Title: Camillo Ricordi
• Organization: University of Miami

ricordi@miami.edu

305-243-6913

Study Officials

• Camillo Ricordi, MD

  University of Miami

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Double-Blinding Trial
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Surgery and Chief, Division of Cellular Transplantation

Model Details: The trial has two groups, each with 12 subjects (n=24). All eligible subjects will be randomized to either the treatment group or standard of care, and randomization will be stratified by ARDS severity.

Study Record Dates

• First Submitted: April 13, 2020
• First Posted: April 21, 2020
• Study Start: April 25, 2020
• Primary Completion: October 31, 2020
• Study Completion: October 31, 2020
• Last Updated: December 6, 2021
• Results First Posted: December 6, 2021

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)