Purpose

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

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
This will be a randomized (1:1 ratio), double blind, parallel design, placebo controlled trial.
Primary Purpose
Treatment
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.

Arm Groups

ArmDescriptionAssigned Intervention
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)
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)

Recruiting Locations

University of Maryland
Baltimore, Maryland 21201
Contact:
Manal Al-Suqi
MaAl-Suqi@som.umaryland.edu

More Details

Status
Recruiting
Sponsor
Icahn School of Medicine at Mount Sinai

Study Contact

Mary Beth Marks
(212) 659-9699
mary.marks@mountsinai.org

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.