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

NCT04333368 | Completed Phase 1

• 2 other identifiers: APHP2003952020-001287-28
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 2

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.

Conditions

Severe Acute Respiratory Syndrome Coronavirus 2; Severe Acute Respiratory Distress Syndrome

Keywords

SARS-CoV2; COVID-19; Acute Respiratory Distress Syndrome; Cell therapy; Mesenchymal stromal cells

Outcome Measures

Primary Outcomes (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

  From baseline to day 7

Secondary Outcomes (15)

• Lung injury score

  From baseline to day 28

• Oxygenation index

  From baseline to day 28

• In-hospital mortality

  From baseline to day 28

• Mortality

  At day 28

• Ventilator-free days

  From baseline to day 28

Study Arms (2)

MSC

EXPERIMENTAL

Biological: Umbilical cord Wharton's jelly-derived human

NaCl

PLACEBO COMPARATOR

Other: NaCl 0.9%

Interventions

Umbilical cord Wharton's jelly-derived human BIOLOGICAL

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.

MSC

NaCl 0.9% OTHER

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

NaCl

Eligibility Criteria

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

You may qualify if:

• Male or female patient, age \> 18 years,
• Laboratory (RT-PCR)-confirmed infection with SARS-CoV2
• Diagnosis of ARDS according to the Berlin definition of ARDS
• Under invasive, non-invasive ventilation or high-flow nasal oxygen therapy (PEEP ≥ 5 cmH2O)
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (2)

Hôpital Pitié-Salpêtrière - APHP

Paris, 75013, France

Location

Hôpital Européen Georges Pompidou - APHP

Paris, 75015, France

Location

Related Publications (2)

• Monsel A, Hauw-Berlemont C, Mebarki M, Heming N, Mayaux J, Nguekap Tchoumba O, Diehl JL, Demoule A, Annane D, Marois C, Demeret S, Weiss E, Voiriot G, Fartoukh M, Constantin JM, Megarbane B, Plantefeve G, Malard-Castagnet S, Burrel S, Rosenzwajg M, Tchitchek N, Boucher-Pillet H, Churlaud G, Cras A, Maheux C, Pezzana C, Diallo MH, Ropers J, Menasche P, Larghero J; APHP STROMA-CoV-2 Collaborative Research Group. Treatment of COVID-19-associated ARDS with mesenchymal stromal cells: a multicenter randomized double-blind trial. Crit Care. 2022 Feb 21;26(1):48. doi: 10.1186/s13054-022-03930-4.

  PMID: 35189925 DERIVED

• Mebarki M, Iglicki N, Marigny C, Abadie C, Nicolet C, Churlaud G, Maheux C, Boucher H, Monsel A, Menasche P, Larghero J, Faivre L, Cras A. Development of a human umbilical cord-derived mesenchymal stromal cell-based advanced therapy medicinal product to treat immune and/or inflammatory diseases. Stem Cell Res Ther. 2021 Nov 13;12(1):571. doi: 10.1186/s13287-021-02637-7.

  PMID: 34774107 DERIVED

MeSH Terms

Conditions

Respiratory Distress Syndrome; COVID-19

Interventions

Sodium Chloride

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Antoine MONSEL, MD, PhD

  Hôpital Pitié-Salpêtrière - Assitance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 29, 2020
• First Posted: April 3, 2020
• Study Start: April 6, 2020
• Primary Completion: October 26, 2021
• Study Completion: October 26, 2021
• Last Updated: February 18, 2022

Record last verified: 2022-02

Locations

FR (2)