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Trial record 1 of 1 for:    Remestemcel | Covid-19 | Cleveland, Ohio, U.S.
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MSCs in COVID-19 ARDS

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ClinicalTrials.gov Identifier: NCT04371393
Recruitment Status : Recruiting
First Posted : May 1, 2020
Last Update Posted : June 19, 2020
Sponsor:
Collaborator:
Mesoblast, Inc.
Information provided by (Responsible Party):
Annetine Gelijns, Icahn School of Medicine at Mount Sinai

Tracking Information
First Submitted Date  ICMJE April 28, 2020
First Posted Date  ICMJE May 1, 2020
Last Update Posted Date June 19, 2020
Actual Study Start Date  ICMJE April 30, 2020
Estimated Primary Completion Date April 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 28, 2020)
Number of all-cause mortality [ Time Frame: 30 days ]
Number of all-cause mortality within 30 days of randomization.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 1, 2020)
  • Number of days alive off mechanical ventilatory support [ Time Frame: 60 days ]
    Number of days alive off mechanical ventilatory support calculated as the number of days, within the 60 days window, that patients were alive and free of mechanical ventilatory support.
  • Number of adverse events [ Time Frame: 30 days ]
    Safety analyses will be assessed by adverse event rates calculated as the ratio of the total number of events over 30 days divided by total patient-time at risk for the specific event from randomization.
  • Number of participants alive at day 7 [ Time Frame: 7 days ]
  • Number of participants alive at day 14 [ Time Frame: 14 days ]
  • Number of participants alive at day 60 [ Time Frame: 60 days ]
  • Number of participants alive at day 90 [ Time Frame: 90 days ]
  • Number of participants with resolution and/or improvement of ARDS [ Time Frame: 7 days ]
    The number and percent of patients with resolution and/or improvement of ARDS at day 7
  • Number of participants with resolution and/or improvement of ARDS [ Time Frame: 14 days ]
    The number and percent of patients with resolution and/or improvement of ARDS at day 14
  • Number of participants with resolution and/or improvement of ARDS [ Time Frame: 21 days ]
    The number and percent of patients with resolution and/or improvement of ARDS at day 21
  • Number of participants with resolution and/or improvement of ARDS [ Time Frame: 30 days ]
    The number and percent of patients with resolution and/or improvement of ARDS at day 30
  • Change from baseline of the severity of ARDS [ Time Frame: baseline and 7 days ]
    Change from baseline of the severity of ARDS according to Berlin Criteria at days 7 post-randomization Change from baseline of the severity of ARDS according to Berlin Criteria at days 7, 14, 21 and 30 post-randomization will be compared between treatment groups using a Cochran-Mantel-Haenszel test stratified by baseline severity.
  • Change from baseline of the severity of ARDS [ Time Frame: baseline and 14 days ]
    Change from baseline of the severity of ARDS according to Berlin Criteria at days 14 post-randomization Change from baseline of the severity of ARDS according to Berlin Criteria at days 7, 14, 21 and 30 post-randomization will be compared between treatment groups using a Cochran-Mantel-Haenszel test stratified by baseline severity.
  • Change from baseline of the severity of ARDS [ Time Frame: baseline and 21 days ]
    Change from baseline of the severity of ARDS according to Berlin Criteria at days 21 post-randomization Change from baseline of the severity of ARDS according to Berlin Criteria at days 7, 14, 21 and 30 post-randomization will be compared between treatment groups using a Cochran-Mantel-Haenszel test stratified by baseline severity.
  • Change from baseline of the severity of ARDS [ Time Frame: baseline and 30 days ]
    Change from baseline of the severity of ARDS according to Berlin Criteria at days 30 post-randomization Change from baseline of the severity of ARDS according to Berlin Criteria at days 7, 14, 21 and 30 post-randomization will be compared between treatment groups using a Cochran-Mantel-Haenszel test stratified by baseline severity.
  • Length of stay [ Time Frame: 12 months ]
    Hospital length of stay
  • Clinical Improvement Scale [ Time Frame: 7 days ]
    Change from baseline in Clinical Improvement Scale at day 7. Clinical Improvement Scale full scale from 1 to 7, with higher score indicating more clinical improvement.
  • Clinical Improvement Scale [ Time Frame: 14 days ]
    Change from baseline in Clinical Improvement Scale at day 14. Full scale from 1 to 7, with higher score indicating more clinical improvement.
  • Clinical Improvement Scale [ Time Frame: 21 days ]
    Change from baseline in Clinical Improvement Scale at day 21. Clinical Improvement Scale full scale from 1 to 7, with higher score indicating more clinical improvement.
  • Clinical Improvement Scale [ Time Frame: 30 days ]
    Change from baseline in Clinical Improvement Scale at day 30. Clinical Improvement Scale full scale from 1 to 7, with higher score indicating more clinical improvement.
  • Change in serum hs-CRP concentration [ Time Frame: baseline and 7 days ]
    Changes from baseline in serum hs-CRP concentration at days 7
  • Change in serum hs-CRP concentration [ Time Frame: baseline and 14 days ]
    Changes from baseline in serum hs-CRP concentration at days 14
  • Change in serum hs-CRP concentration [ Time Frame: baseline and 21 days ]
    Changes from baseline in serum hs-CRP concentration at days 21
  • Change in serum hs-CRP concentration [ Time Frame: baseline and 30 days ]
    Changes from baseline in serum hs-CRP concentration at days 30
  • Change in IL-6 inflammatory marker level [ Time Frame: baseline and 7 days ]
    Changes from baseline in IL-6 inflammatory marker level at 7 days
  • Change in IL-6 inflammatory marker level [ Time Frame: baseline and 14 days ]
    Changes from baseline in IL-6 inflammatory marker level at 14 days
  • Change in IL-6 inflammatory marker level [ Time Frame: baseline and 21 days ]
    Changes from baseline in IL-6 inflammatory marker level at 21 days
  • Change in IL-6 inflammatory marker level [ Time Frame: baseline and 30 days ]
    Changes from baseline in IL-6 inflammatory marker level at 30 days
  • Change in IL-8 inflammatory marker level [ Time Frame: baseline and 7 days ]
    Changes from baseline in IL-6 inflammatory marker level at 7 days
  • Change in IL-8 inflammatory marker level [ Time Frame: baseline and 14 days ]
    Changes from baseline in IL-6 inflammatory marker level at 14 days
  • Change in IL-8 inflammatory marker level [ Time Frame: baseline and 21 days ]
    Changes from baseline in IL-6 inflammatory marker level at 21 days
  • Change in IL-8 inflammatory marker level [ Time Frame: baseline and 30 days ]
    Changes from baseline in IL-6 inflammatory marker level at 30 days
  • Change in TNF-alpha inflammatory marker level [ Time Frame: baseline and 7 days ]
    Changes from baseline in TNF-alpha inflammatory marker level at 7 days
  • Change in TNF-alpha inflammatory marker level [ Time Frame: baseline and 14 days ]
    Changes from baseline in TNF-alpha inflammatory marker level at 14 days
  • Change in TNF-alpha inflammatory marker level [ Time Frame: baseline and 21 days ]
    Changes from baseline in TNF-alpha inflammatory marker level at 21 days
  • Change in TNF-alpha inflammatory marker level [ Time Frame: baseline and 30 days ]
    Changes from baseline in TNF-alpha inflammatory marker level at 30 days
Original Secondary Outcome Measures  ICMJE
 (submitted: April 28, 2020)
  • Number of days alive off mechanical ventilatory support [ Time Frame: 60 days ]
    Number of days alive off mechanical ventilatory support calculated as the number of days, within the 60 days window, that patients were alive and free of mechanical ventilatory support.
  • Number of adverse events [ Time Frame: 30 days ]
    Safety analyses will be assessed by adverse event rates calculated as the ratio of the total number of events over 30 days divided by total patient-time at risk for the specific event from randomization.
  • Number of participants alive at day 7 [ Time Frame: 7 days ]
  • Number of participants alive at day 14 [ Time Frame: 14 days ]
  • Number of participants alive at day 60 [ Time Frame: 60 days ]
  • Number of participants alive at day 90 [ Time Frame: 90 days ]
  • Number of participants with resolution and/or improvement of ARDS [ Time Frame: 7 days ]
    The number and percent of patients with resolution and/or improvement of ARDS at day 7
  • Number of participants with resolution and/or improvement of ARDS [ Time Frame: 14 days ]
    The number and percent of patients with resolution and/or improvement of ARDS at day 14
  • Number of participants with resolution and/or improvement of ARDS [ Time Frame: 21 days ]
    The number and percent of patients with resolution and/or improvement of ARDS at day 21
  • Number of participants with resolution and/or improvement of ARDS [ Time Frame: 30 days ]
    The number and percent of patients with resolution and/or improvement of ARDS at day 30
  • Change from baseline of the severity of ARDS [ Time Frame: baseline and 7 days ]
    Change from baseline of the severity of ARDS according to Berlin Criteria at days 7 post-randomization Change from baseline of the severity of ARDS according to Berlin Criteria at days 7, 14, 21 and 30 post-randomization will be compared between treatment groups using a Cochran-Mantel-Haenszel test stratified by baseline severity.
  • Change from baseline of the severity of ARDS [ Time Frame: baseline and 14 days ]
    Change from baseline of the severity of ARDS according to Berlin Criteria at days 14 post-randomization Change from baseline of the severity of ARDS according to Berlin Criteria at days 7, 14, 21 and 30 post-randomization will be compared between treatment groups using a Cochran-Mantel-Haenszel test stratified by baseline severity.
  • Change from baseline of the severity of ARDS [ Time Frame: baseline and 21 days ]
    Change from baseline of the severity of ARDS according to Berlin Criteria at days 21 post-randomization Change from baseline of the severity of ARDS according to Berlin Criteria at days 7, 14, 21 and 30 post-randomization will be compared between treatment groups using a Cochran-Mantel-Haenszel test stratified by baseline severity.
  • Change from baseline of the severity of ARDS [ Time Frame: baseline and 30 days ]
    Change from baseline of the severity of ARDS according to Berlin Criteria at days 30 post-randomization Change from baseline of the severity of ARDS according to Berlin Criteria at days 7, 14, 21 and 30 post-randomization will be compared between treatment groups using a Cochran-Mantel-Haenszel test stratified by baseline severity.
  • Length of stay [ Time Frame: 12 months ]
    Hospital length of stay
  • Clinical Improvement Scale [ Time Frame: 7 days ]
    Change from baseline in Clinical Improvement Scale at day 7. Clinical Improvement Scale full scale from 1 to 7, with higher score indicating more clinical improvement.
  • Clinical Improvement Scale [ Time Frame: 14 days ]
    Change from baseline in Clinical Improvement Scale at day 14. Full scale from 1 to 7, with higher score indicating more clinical improvement.
  • Clinical Improvement Scale [ Time Frame: 21 days ]
    Change from baseline in Clinical Improvement Scale at day 21. Clinical Improvement Scale full scale from 1 to y, with higher score indicating more clinical improvement.
  • Clinical Improvement Scale [ Time Frame: 30 days ]
    Change from baseline in Clinical Improvement Scale at day 30. Clinical Improvement Scale full scale from 1 to 7, with higher score indicating more clinical improvement.
  • Change in serum hs-CRP concentration [ Time Frame: baseline and 7 days ]
    Changes from baseline in serum hs-CRP concentration at days 7
  • Change in serum hs-CRP concentration [ Time Frame: baseline and 14 days ]
    Changes from baseline in serum hs-CRP concentration at days 14
  • Change in serum hs-CRP concentration [ Time Frame: baseline and 21 days ]
    Changes from baseline in serum hs-CRP concentration at days 21
  • Change in serum hs-CRP concentration [ Time Frame: baseline and 30 days ]
    Changes from baseline in serum hs-CRP concentration at days 30
  • Change in IL-6 inflammatory marker level [ Time Frame: baseline and 7 days ]
    Changes from baseline in IL-6 inflammatory marker level at 7 days
  • Change in IL-6 inflammatory marker level [ Time Frame: baseline and 14 days ]
    Changes from baseline in IL-6 inflammatory marker level at 14 days
  • Change in IL-6 inflammatory marker level [ Time Frame: baseline and 21 days ]
    Changes from baseline in IL-6 inflammatory marker level at 21 days
  • Change in IL-6 inflammatory marker level [ Time Frame: baseline and 30 days ]
    Changes from baseline in IL-6 inflammatory marker level at 30 days
  • Change in IL-8 inflammatory marker level [ Time Frame: baseline and 7 days ]
    Changes from baseline in IL-6 inflammatory marker level at 7 days
  • Change in IL-8 inflammatory marker level [ Time Frame: baseline and 14 days ]
    Changes from baseline in IL-6 inflammatory marker level at 14 days
  • Change in IL-8 inflammatory marker level [ Time Frame: baseline and 21 days ]
    Changes from baseline in IL-6 inflammatory marker level at 21 days
  • Change in IL-8 inflammatory marker level [ Time Frame: baseline and 30 days ]
    Changes from baseline in IL-6 inflammatory marker level at 30 days
  • Change in TNF-alpha inflammatory marker level [ Time Frame: baseline and 7 days ]
    Changes from baseline in TNF-alpha inflammatory marker level at 7 days
  • Change in TNF-alpha inflammatory marker level [ Time Frame: baseline and 14 days ]
    Changes from baseline in TNF-alpha inflammatory marker level at 14 days
  • Change in TNF-alpha inflammatory marker level [ Time Frame: baseline and 21 days ]
    Changes from baseline in TNF-alpha inflammatory marker level at 21 days
  • Change in TNF-alpha inflammatory marker level [ Time Frame: baseline and 30 days ]
    Changes from baseline in TNF-alpha inflammatory marker level at 30 days
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE MSCs in COVID-19 ARDS
Official Title  ICMJE Mesenchymal Stem Cells for the Treatment of Moderate to Severe COVID-19 Acute Respiratory Distress Syndrome
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.

Detailed Description

This will be a randomized (1:1 ratio), double blind, parallel design, placebo controlled trial. Randomization will be stratified by clinical center and by moderate versus severe ARDS. The study is designed to have three interim analyses for stopping accrual early for efficacy and futility when 30%, 45% and 60% of the 300 patients have reached the primary endpoint using Bayesian predictive probabilities.

Patients will be randomized in a 1:1 allocation to intravenous infusion of MSCs (remestemcel-L) plus standard of care versus placebo plus standard of care for the treatment of COVID-19 related ARDS:

  • Group 1: 2x10^6 MSC/kg of body weight plus standard of care, administered twice during the first week, with the second infusion at 4 days following the first infusion (± 1 day)
  • Group 2: Placebo (Plasma-Lyte) plus standard of care, administered twice during the first week, with the second infusion at 4 days following the first infusion (± 1 day) (control)

MSCs and placebo will initially be administered intravenously in the dose defined above at randomization. The rate of infusion may be tailored to the patient's respiratory status and fluid status, but the duration of infusion should not exceed 60 minutes.

Patients will be followed for 90 days post randomization, with assessment of pulmonary symptoms at 6 and 12 months.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
This will be a randomized (1:1 ratio), double blind, parallel design, placebo controlled trial.
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking Description:
This is a randomized clinical trial, in which the patients and investigators are masked to treatment assignment.
Primary Purpose: Treatment
Condition  ICMJE
  • Mesenchymal Stromal Cells
  • Remestemcel-L
  • Acute Respiratory Distress Syndrome
  • COVID
Intervention  ICMJE
  • Biological: Remestemcel-L
    administered twice during the first week, with the second infusion at 4 days following the first injection (± 1 day)
  • Drug: Placebo
    administered twice during the first week, with second infusion at 4 days following the first injection (± 1 day)
Study Arms  ICMJE
  • Experimental: Remestemcel-L Plus Standard of Care
    Intravenous infusion of remestemcel-L 2x10^6 MSC/kg of body weight plus standard of care
    Intervention: Biological: Remestemcel-L
  • Placebo Comparator: Placebo Plus Standard of Care
    Placebo (Plasma-Lyte) plus standard of care
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 28, 2020)
300
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 2022
Estimated Primary Completion Date April 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria

  • 18 years or older
  • Patient has coronavirus disease 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 computed 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) serum level >4.0 mg/dL
  • Acute Physiologic and Chronic Health Evaluation (APACHE IV) score >5
  • The patient or his/her legally authorized representative (LAR) is able to provide informed consent

Exclusion Criteria

  • 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 untreated HIV infection
  • Patients who have been intubated for more than 72 hours
  • Creatinine clearance less than 30 mL/minute
  • LFTs (ALT or AST) > 5x 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Mary Beth Marks (212) 659-9699 mary.marks@mountsinai.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04371393
Other Study ID Numbers  ICMJE GCO 08-1078-0014
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: All of the individual participant data collected during the trial, after deidentification.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Supporting Materials: 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.
Responsible Party Annetine Gelijns, Icahn School of Medicine at Mount Sinai
Study Sponsor  ICMJE Icahn School of Medicine at Mount Sinai
Collaborators  ICMJE Mesoblast, Inc.
Investigators  ICMJE
Principal Investigator: Annetine C Gelijns, PhD Icahn School of Medicine at Mount Sinai
Study Director: Michael Mack, MD Baylor Research Institute
Study Director: Peter Smith, MD Duke University
PRS Account Icahn School of Medicine at Mount Sinai
Verification Date June 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP