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Cell Therapy Using Umbilical Cord-derived Mesenchymal Stromal Cells in SARS-CoV-2-related ARDS (STROMA-CoV2)

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ClinicalTrials.gov Identifier: NCT04333368
Recruitment Status : Recruiting
First Posted : April 3, 2020
Last Update Posted : May 21, 2020
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Brief Summary:

Whereas the pandemic due do Covid-19 continues to spread, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes Severe Acute Respiratory Distress Syndrome in 30% of patients with a 30%-60% mortality rate for those requiring hospitalization in an intensive care unit. The main physio-pathological hallmark is an acute pulmonary inflammation. Currently, there is no treatment.

Mesenchymal stem cells (MSC) feature several attractive characteristics: ease of procurement, high proliferation potential, capacity to home to inflammatory sites, anti-inflammatory, anti-fibrotic and immunomodulatory properties. If all MSC share several characteristics regardless of the tissue source, the highest productions of bioactive molecules and the strongest immunomodulatory properties are yielded by those from the Wharton's jelly of the umbilical cord. An additional advantage is that they can be scaled-up to generate banks of cryofrozen and thus readily available products. These cells have already been tested in several clinical trials with an excellent safety record.

The objective of this project is to treat intubated-ventilated patients presenting with a SARS-CoV2-related Acute Respiratory Distress Syndrome (ARDS) of less than 96 hours by three intravenous infusions of umbilical cord Wharton's jelly-derived mesenchymal stromal cells (UC-MSC) one every other day (duration of the treatment: one week). The primary endpoint is the PaO2/FiO2 ratio at day 7. The evolution of several inflammatory markers, T regulatory lymphocytes and donor-specific antibodies will also be monitored. The trial will include 40 patients, of whom 20 will be cell-treated while the remaining 20 patients will be injected with a placebo solution in addition to the standard of care. Given the pathophysiology of SARS-CoV2, it is thus sound to hypothesize that the intravenous administration of UC-MSC during the initial phase of ARDS could control inflammation, accelerate its recovery with improved oxygenation, reduced mechanical ventilation and ventilation weaning time and therefore reduced length of stay in intensive care.

The feasibility of the project is supported by the expertise of the Meary Cell and Gene Therapy Center, which is approved for the production of Advanced Therapy Medicinal Products and has already successfully prepared the first batches of cells, as well as by the involvement of a cardiac surgery team which will leverage its experience with stem cells for the treatment of heart failure to make it relevant to the Stroma-Cov-2 project.


Condition or disease Intervention/treatment Phase
Severe Acute Respiratory Syndrome Coronavirus 2 Severe Acute Respiratory Distress Syndrome Biological: Umbilical cord Wharton's jelly-derived human Other: NaCl 0.9% Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Cell Therapy Using Umbilical Cord-derived Mesenchymal Stromal Cells in SARS-CoV-2-related ARDS
Actual Study Start Date : April 6, 2020
Estimated Primary Completion Date : August 31, 2020
Estimated Study Completion Date : July 31, 2021


Arm Intervention/treatment
Experimental: MSC Biological: Umbilical cord Wharton's jelly-derived human
Umbilical cord Wharton's jelly-derived human MSC (at the dose of 1 Million / kg) will be administered via a peripheral or central venous line over 60 minutes, using tubing with a 200-μm filter. Cells, in a 150 mL volume, will be delivered at D1 - D3 - D5.

Placebo Comparator: NaCl Other: NaCl 0.9%
NaCl 0.9% (150 mL) given via an intravenous route at D1 - D3 - D5




Primary Outcome Measures :
  1. Respiratory efficacy evaluated by the increase in PaO2/FiO2 ratio from baseline to day 7 in the experimental group compared with the placebo group [ Time Frame: From baseline to day 7 ]

Secondary Outcome Measures :
  1. Lung injury score [ Time Frame: From baseline to day 28 ]
  2. Oxygenation index [ Time Frame: From baseline to day 28 ]
  3. In-hospital mortality [ Time Frame: From baseline to day 28 ]
  4. Mortality [ Time Frame: At day 28 ]
  5. Ventilator-free days [ Time Frame: From baseline to day 28 ]
  6. Number of days between randomization and the first day the patient meets weaning criteria o Number of days between randomization and the first day the patient meets PaO2/FiO2 > 200 (out of a prone positioning session) [ Time Frame: From baseline to day 28 ]
  7. Cumulative use of sedatives [ Time Frame: From baseline to day 28 ]
  8. Cumulative duration of use of sedatives [ Time Frame: From baseline to day 28 ]
  9. Cumulative duration of use of neuromuscular blocking agents (other than used for intubation) [ Time Frame: From baseline to day 28 ]
  10. Cumulative use of neuromuscular blocking agents (other than used for intubation) [ Time Frame: From baseline to day 28 ]
  11. ICU-acquired weakness and delirium [ Time Frame: From baseline to day 28 ]
  12. Treatment-induced toxicity rate and adverse events up to day 28 [ Time Frame: From baseline to day 28 ]
  13. Quality of life at one year (EQ5D-3L quality of life questionnaire) [ Time Frame: At 6 months and 12 months ]
  14. Measurements of plasmatic cytokines (IL1, IL6, IL8, TNF-alpha, IL10, TGF-beta, sRAGE, Ang2) level [ Time Frame: At day 1, 3, 5, 7 and 14 ]
  15. Anti-HLA antibodies plasmatic dosage [ Time Frame: From baseline to day 14, and at 6 months ]


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

Inclusion Criteria:

  • Male or female patient, age > 18 years, intubated and mechanically ventilated
  • Laboratory (RT-PCR)-confirmed infection with SARS-CoV2
  • Diagnosis of ARDS according to the Berlin definition of ARDS
  • Onset of ARDS <96 hours
  • Patient with French Social Security System
  • Provision of a written informed consent by the designated substitute decision maker, if present. In the event of absence, the patient can be included by investigator's decision alone.

Exclusion Criteria:

  • Previous history of ARDS in the last month
  • Chronic respiratory diseases requiring long-term oxygen therapy and/or long-term respiratory assistance
  • Allogeneic bone marrow transplantation
  • Active cancer
  • Liver cirrhosis with basal Child and Pugh of C
  • Pulmonary fibrosis
  • Patient with end-of-life decision
  • Patient not expected to survive for 24 hours
  • Patient who received an organ transplant
  • Woman known to be pregnant or lactating
  • Patient already enrolled in another interventional pharmacotherapy protocol on COVID-19
  • Patient has burns to ≥15% of their total body surface area
  • Patient is receiving extra-corporeal membrane oxygenation, high-frequency oscillatory ventilation or any form of extra-corporeal lung support
  • Patient under tutelage

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): NCT04333368


Contacts
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Contact: Antoine MONSEL, MD, PhD 0184827399 antoine.monsel@aphp.fr
Contact: Philippe MENASCHÉ, MD, PhD 01 56 09 36 22 philippe.menasche@aphp.fr

Locations
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France
Hôpital Pitié-Salpêtrière - APHP Recruiting
Paris, France, 75013
Contact: Antoine A MONSEL, MD, PhD    0184827399    antoine.monsel@aphp.fr   
Hôpital Européen Georges Pompidou - APHP Recruiting
Paris, France, 75015
Contact: Philippe MENASCHE, MD, PhD    01 56 09 36 22    philippe.menasche@aphp.fr   
Contact: Jean-Luc DIEHL, MD, PhD       jean-luc.diehl@aphp.fr   
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
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Principal Investigator: Antoine MONSEL, MD, PhD Hôpital Pitié-Salpêtrière - Assitance Publique - Hôpitaux de Paris
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Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT04333368    
Other Study ID Numbers: APHP200395
2020-001287-28 ( EudraCT Number )
First Posted: April 3, 2020    Key Record Dates
Last Update Posted: May 21, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Assistance Publique - Hôpitaux de Paris:
SARS-CoV2
COVID-19
Acute Respiratory Distress Syndrome
Cell therapy
Mesenchymal stromal cells
Additional relevant MeSH terms:
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Coronavirus Infections
Severe Acute Respiratory Syndrome
Respiratory Distress Syndrome, Newborn
Respiratory Distress Syndrome, Adult
Acute Lung Injury
Syndrome
Disease
Pathologic Processes
Lung Diseases
Respiratory Tract Diseases
Respiration Disorders
Infant, Premature, Diseases
Infant, Newborn, Diseases
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Virus Diseases
Lung Injury
Respiratory Tract Infections