NCT04333368: STROMA-CoV2

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

Completed Phase 1, PHASE2 Last updated 18 February 2022

What this trial tests

Phase 1, PHASE2 trial testing Umbilical cord Wharton's jelly-derived human in Severe Acute Respiratory Syndrome Coronavirus 2 in 47 participants. Completed in 26 October 2021.

Timeline

6 April 2020

Primary endpoint
26 October 2021

26 October 2021

Quick facts

Lead sponsor	Assistance Publique - Hôpitaux de Paris
Phase	Phase 1, PHASE2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	triple
Primary purpose	treatment
Enrollment	47
Start date	6 April 2020
Primary completion	26 October 2021
Estimated completion	26 October 2021
Sites	2 locations across France

Drugs / interventions tested

• Umbilical cord Wharton's jelly-derived human — full drug profile →
• NaCl 0.9%

Conditions studied

• Severe Acute Respiratory Syndrome Coronavirus 2 — all drugs for Severe Acute Respiratory Syndrome Coronavirus 2 →
• Severe Acute Respiratory Distress Syndrome — all drugs for Severe Acute Respiratory Distress Syndrome →

Sponsor

Assistance Publique - Hôpitaux de Paris — full company profile →

Who can join

18 and older, any sex, with Severe Acute Respiratory Syndrome Coronavirus 2 or Severe Acute Respiratory Distress Syndrome. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Cytokine storm and leukocyte changes in mild versus severe SARS-CoV-2 infection: Review of 3939 COVID-19 patients in China and emerging pathogenesis and therapy concepts.
   Wang J, Jiang M, Chen X, Montaner LJ. · · 2020 · cited 551× · PMID 32534467 · DOI 10.1002/jlb.3covr0520-272r
2. COVID-19 and Cancer: a Comprehensive Review.
   Gosain R, Abdou Y, Singh A, Rana N, et al · · 2020 · cited 187× · PMID 32385672 · DOI 10.1007/s11912-020-00934-7
3. Immunomodulatory Mechanisms of Mesenchymal Stem Cells and Their Potential Clinical Applications.
   Huang Y, Wu Q, Tam PKH. · · 2022 · cited 143× · PMID 36077421 · DOI 10.3390/ijms231710023
4. Human umbilical cord-derived mesenchymal stem/stromal cells: a promising candidate for the development of advanced therapy medicinal products.
   Mebarki M, Abadie C, Larghero J, Cras A. · · 2021 · cited 116× · PMID 33637125 · DOI 10.1186/s13287-021-02222-y
5. Treatment of COVID-19-associated ARDS with mesenchymal stromal cells: a multicenter randomized double-blind trial.
   Monsel A, Hauw-Berlemont C, Mebarki M, Heming N, et al · · 2022 · cited 83× · PMID 35189925 · DOI 10.1186/s13054-022-03930-4
6. Is COVID-19 a New Hematologic Disease?
   Debuc B, Smadja DM. · · 2021 · cited 70× · PMID 32399806 · DOI 10.1007/s12015-020-09987-4
7. The mechanism underlying extrapulmonary complications of the coronavirus disease 2019 and its therapeutic implication.
   Ning Q, Wu D, Wang X, Xi D, et al · · 2022 · cited 64× · PMID 35197452 · DOI 10.1038/s41392-022-00907-1
8. Immunobiology and immunotherapy of COVID-19: A clinically updated overview.
   Esmaeilzadeh A, Elahi R. · · 2021 · cited 59× · PMID 33022076 · DOI 10.1002/jcp.30076