MSCs in COVID-19 ARDS

NCT04371393 | Terminated Phase 3 DMC FDA Drug

• 1 other identifier: GCO 08-1078-0014
• Study Type: interventional
• Target: 223
• Locations: 1 country
• Sites: 21

Brief Summary

The mortality rate in SARS-CoV-2-related severe ARDS is high despite treatment with antivirals, glucocorticoids, immunoglobulins, and ventilation. Preclinical and clinical evidence indicate that MSCs migrate to the lung and respond to the pro-inflammatory lung environment by releasing anti-inflammatory factors reducing the proliferation of pro-inflammatory cytokines while modulating regulatory T cells and macrophages to promote resolution of inflammation. Therefore, MSCs may have the potential to increase survival in management of COVID-19 induced ARDS. The primary objective of this phase 3 trial is to evaluate the efficacy and safety of the addition of the mesenchymal stromal cell (MSC) remestemcel-L plus standard of care compared to placebo plus standard of care in patients with acute respiratory distress syndrome (ARDS) due to SARS-CoV-2. The secondary objective is to assess the impact of MSCs on inflammatory biomarkers.

Conditions

Mesenchymal Stromal Cells; Remestemcel-L; Acute Respiratory Distress Syndrome; COVID

Keywords

mesenchymal stem cells; SARS-CoV-2; cytokine storm

Outcome Measures

Primary Outcomes (1)

• Number of all-cause mortality

  Number of all-cause mortality within 30 days of randomization.

  30 days

Secondary Outcomes (40)

• Number of days alive off mechanical ventilatory support

  60 days

• Number of adverse events

  30 days

• Number of participants alive at day 7

  7 days

• Number of participants alive at day 14

  14 days

• Number of participants alive at day 60

  60 days

Study Arms (2)

Remestemcel-L Plus Standard of Care

EXPERIMENTAL

Intravenous infusion of remestemcel-L 2x10\^6 MSC/kg of body weight plus standard of care

Biological: Remestemcel-L

Placebo Plus Standard of Care

PLACEBO COMPARATOR

Placebo (Plasma-Lyte) plus standard of care

Drug: Placebo

Interventions

Remestemcel-L BIOLOGICAL

administered twice during the first week, with the second infusion at 4 days following the first injection (± 1 day)

Remestemcel-L Plus Standard of Care

Placebo DRUG

administered twice during the first week, with second infusion at 4 days following the first injection (± 1 day)

Placebo Plus Standard of Care

Eligibility Criteria

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

You may qualify if:

• years or older
• Patient has SARS-CoV-2 (COVID-19) confirmed by real-time reverse transcription polymerase chain reaction (RT-PCR) assay or other diagnostic test
• Patient requiring mechanical ventilatory support with moderate to severe ARDS as determined by the following criteria (adapted from the Berlin criteria)
• Bilateral opacities must be present on a chest radiograph or computerized tomographic (CT) scan. These opacities are not fully explained by pleural effusions, lobar collapse, lung collapse, or pulmonary nodules.
• Respiratory failure not fully explained by cardiac failure or fluid overload.
• Moderate to severe impairment of oxygenation must be present, as defined by the ratio of arterial oxygen tension to fraction of inspired oxygen (PaO2/FiO2). The severity of the hypoxemia defines the severity of the ARDS:
• Moderate ARDS: PaO2/FiO2 \>100 mmHg and ≤200 mmHg, on ventilator settings that include PEEP ≥5 cm H2O OR
• Severe ARDS: PaO2/FiO2 ≤100 mmHg on ventilator settings that include PEEP ≥5 cm H2O
• High sensitivity C-Reactive Protein (hs-CRP) or CRP serum level \>4.0 mg/dL
• Acute Physiologic and Chronic Health Evaluation (APACHE IV) score \>5
• Creatinine clearance of ≥ 30 mL/minute OR a creatinine clearance of 20-29 mL/minute with urine output of ≥0.3 mLs/kg/hour over the last 8 hours or ≥500 mLs over the last 24 hours
• The patient or his/her legally authorized representative (LAR) is able to provide informed consent

You may not qualify if:

• Currently receiving extracorporeal membrane oxygenation (ECMO) or high frequency oscillatory ventilation (HFOV)
• Females who are pregnant or lactating
• Patients with established positive bacterial blood cultures prior to enrollment or suspicion of superimposed bacterial pneumonia
• Patients with BMI \>55
• Patients with untreated HIV infection
• Patients with malignancy who are within 12 months of active treatment with any chemotherapy, radiation or immunotherapy.
• Patients who have been intubated for more than 72 hours in total at the time of randomization
• Creatinine clearance less than 20 mL/minute or receiving renal replacement therapy
• LFTs (isolated ALT or AST) \> 8x upper limit of normal or \> 5x upper limit of normal in the setting of other liver function abnormalities (i.e., total bilirubin ≥ 2x upper limit of normal)
• Known hypersensitivity to DMSO or to porcine or bovine proteins
• History of prior respiratory disease with requirement for supplemental oxygen
• Any end-stage organ disease which in the opinion of the investigator may possibly affect the safety of remestemcel-L treatment
• Receiving an investigational cellular therapy agent

Sponsors & Collaborators

• Icahn School of Medicine at Mount Sinai: lead
• Mesoblast, Inc.: collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (21)

Dignity Health

Gilbert, Arizona, 85297, United States

Location

University of Southern California

Los Angeles, California, 90033, United States

Location

Stanford University

Stanford, California, 94305, United States

Location

Emory University

Atlanta, Georgia, 30308, United States

Location

Lutheran Hospital

Fort Wayne, Indiana, 46825, United States

Location

Ochsner Clinic

New Orleans, Louisiana, 70121, United States

Location

Maine Medical Center

Portland, Maine, 04102, United States

Location

University of Maryland

Baltimore, Maryland, 21201, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Dartmouth-Hitchcock

Lebanon, New Hampshire, 03766, United States

Location

New York University Langone Health

New York, New York, 10016, United States

Location

Mount Sinai Health

New York, New York, 10029, United States

Location

Northwell Health

New York, New York, 10075, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

WakeMed

Raleigh, North Carolina, 27610, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

University of Pennsylvania Health System

Philadelphia, Pennsylvania, 19104, United States

Location

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

Baylor, Smith & White

Plano, Texas, 75093, United States

Location

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

MeSH Terms

Conditions

Respiratory Distress Syndrome; Cytokine Release Syndrome

Interventions

remestemcel-l

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Study Officials

• Annetine C Gelijns, PhD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

• Michael Mack, MD

  Baylor Research Institute

  STUDY DIRECTOR

• Peter Smith, MD

  Duke University

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This is a randomized clinical trial, in which the patients and investigators are masked to treatment assignment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chair, Department of Population Health Science & Policy

Model Details: This will be a randomized (1:1 ratio), double blind, parallel design, placebo controlled trial.

Study Record Dates

• First Submitted: April 28, 2020
• First Posted: May 1, 2020
• Study Start: April 30, 2020
• Primary Completion: January 14, 2021
• Study Completion: January 2, 2022
• Last Updated: April 25, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: De-identified study data sets must be submitted to the designated NHLBI Program Official no later than 3 years after the end of the clinical activity (final patient follow-up, etc.) or 2 years after the main paper of the trial has been published, whichever comes first. Data are prepared by the study coordinating center and sent to the designated PO for review prior to release.
• Access Criteria: Anyone who wishes to access the data.

Locations

US (21)