https://clinicaltrials.gov/ct2/show/NCT04371393?term=Stem+cells&cond=COVID&draw=2&rank=24

MSCs inCOVID-19 ARDS

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government.Know the risks and potential benefitsof clinical studies and talk to your health care provider before participating. Read ourdisclaimerfor details.

	ClinicalTrials.gov Identifier: NCT04371393
1	Recruitment Status: Not yet recruiting First Posted: May 1, 2020 Last Update Posted: May 1, 2020 SeeContacts and Locations

Sponsor:

Icahn School of Medicine at Mount Sinai

Collaborator:

Mesoblast, Inc.

Information provided by (Responsible Party):

Annetine Gelijns, Icahn School of Medicine at Mount Sinai

• Study Details
• Tabular View
• No Results Posted
• Disclaimer
• How to Read a Study Record

Study Description

Go to

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 Tcellsand 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 stromalcell(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.

	Condition or disease	Intervention/treatment	Phase
1	Mesenchymal StromalCellsRemestemcel-L	Biological: Remestemcel-L®Drug: Placebo	Phase 3

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 Design

Go to

	Study Type:	Interventional (Clinical Trial)
1	EstimatedEnrollment:	300 participants
2	Allocation:	Randomized
3	Intervention Model:	Parallel Assignment
4	Intervention Model Description:	This will be a randomized (1:1 ratio), double blind, parallel design, placebo controlled trial.
5	Masking:	Triple (Participant, Investigator, Outcomes Assessor)
6	Masking Description:	This is a randomized clinical trial, in which the patients and investigators are masked to treatment assignment.
7	Primary Purpose:	Treatment
8	Official Title:	MesenchymalStem Cellsfor the Treatment of Moderate to SevereCOVID-19 Acute Respiratory Distress Syndrome
9	EstimatedStudy Start Date:	April 2020
10	EstimatedPrimary Completion Date:	April 2021
11	EstimatedStudy Completion Date:	April 2022

Resource links provided by the National Library of Medicine

Genetic and Rare Diseases Information Centerresources:Respiratory Distress Syndrome, InfantAcute Respiratory Distress Syndrome

U.S. FDA Resources

Arms and Interventions

Go to

	Arm	Intervention/treatment
1	Experimental: Remestemcel-L® Plus Standard of Care Intravenous infusion of remestemcel-L® 2x10^6 MSC/kg of body weight plus standard of care	Biological: Remestemcel-L® administered twice during the first week, with the second infusion at 4 days following the first injection (± 1 day)
2	Placebo Comparator: Placebo Plus Standard of Care Placebo (Plasma-Lyte) plus standard of care	Drug: Placebo administered twice during the first week, with second infusion at 4 days following the first injection (± 1 day)

Outcome Measures

Go to

Primary Outcome Measures:

1. Number of all-cause mortality [ Time Frame: 30 days ]
   Number of all-cause mortality within 30 days of randomization.

Secondary Outcome Measures:

1. 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.
2. 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.
3. Number of participants alive at day 7 [ Time Frame: 7 days ]
4. Number of participants alive at day 14 [ Time Frame: 14 days ]
5. Number of participants alive at day 60 [ Time Frame: 60 days ]
6. Number of participants alive at day 90 [ Time Frame: 90 days ]
7. 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
8. 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
9. 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
10. 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
11. 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.
12. 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.
13. 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.
14. 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.
15. Length of stay [ Time Frame: 12 months ]
    Hospital length of stay
16. 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.
17. 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.
18. 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.
19. 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.
20. Change in serum hs-CRP concentration [ Time Frame: baseline and 7 days ]
    Changes from baseline in serum hs-CRP concentration at days 7
21. Change in serum hs-CRP concentration [ Time Frame: baseline and 14 days ]
    Changes from baseline in serum hs-CRP concentration at days 14
22. Change in serum hs-CRP concentration [ Time Frame: baseline and 21 days ]
    Changes from baseline in serum hs-CRP concentration at days 21
23. Change in serum hs-CRP concentration [ Time Frame: baseline and 30 days ]
    Changes from baseline in serum hs-CRP concentration at days 30
24. 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
25. 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
26. 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
27. 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
28. 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
29. 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
30. 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
31. 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
32. 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
33. 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
34. 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
35. 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

Eligibility Criteria

Go to

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information,Learn About Clinical Studies.

	Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
1	Sexes Eligible for Study:	All
2	Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Go to

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number):NCT04371393

Contacts

	Contact: Mary Beth Marks	(212) 659-9699	[email protected]

Sponsors and Collaborators

Icahn School of Medicine at Mount Sinai

Mesoblast, Inc.

Investigators

	Principal Investigator:	Annetine C Gelijns, PhD	Icahn School of Medicine at Mount Sinai
1	Study Director:	Michael Mack, MD	Baylor Research Institute
2	Study Director:	Peter Smith, MD	Duke University

More Information

Go to

Responsible Party:	Annetine Gelijns, Chair, Department of Population Health Science & Policy, Icahn School of Medicine at Mount Sinai
ClinicalTrials.gov Identifier:	NCT04371393History of Changes
Other Study ID Numbers:	GCO 08-1078-0014
First Posted:	May 1, 2020 Key Record Dates
Last Update Posted:	May 1, 2020
Last Verified:	April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Yes
Plan Description:	All of the individual participant data collected during the trial, after deidentification.
Supporting Materials:	Study Protocol Statistical Analysis Plan (SAP) Informed Consent Form (ICF) Clinical Study Report (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.

Studies a U.S. FDA-regulated Drug Product:	Yes
Studies a U.S. FDA-regulated Device Product:	No