Bone Marrow Mesenchymal Stem Cell-Derived Extracellular Vesicle Infusion for the Treatment of Respiratory Failure From COVID-19: A Randomized, Placebo-Controlled Dosing Clinical Trial.
| Autor: | Lightner AL; Direct Biologics, LLC, Austin, TX. Electronic address: ALightner@directbiologics.com., Sengupta V; Direct Biologics, LLC, Austin, TX., Qian S; Direct Biologics, LLC, Austin, TX., Ransom JT; Direct Biologics, LLC, Austin, TX., Suzuki S; Direct Biologics, LLC, Austin, TX., Park DJ; Providence St Jude Medical Center/Providence Medical Foundation, Fullerton, CA., Melson TI; Helen Keller Hospital, Sheffield, AL., Williams BP; Covenant Health, Lubbock, TX., Walsh JJ; Donald Guthrie Foundation, Sayre, PA., Awili M; PRX Research, Mesquite, TX. |
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| Jazyk: | angličtina |
| Zdroj: | Chest [Chest] 2023 Dec; Vol. 164 (6), pp. 1444-1453. Date of Electronic Publication: 2023 Jun 23. |
| DOI: | 10.1016/j.chest.2023.06.024 |
| Abstrakt: | Background: Bone marrow mesenchymal stem cell (BM-MSC)-derived extracellular vesicles (ExoFlo) convey the immunomodulatory and regenerative properties of intact BM-MSCs. This study aimed to determine the safety and efficacy of ExoFlo as treatment for moderate to severe ARDS in patients with severe COVID-19. Research Question: Do two doses of ExoFlo safely reduce mortality in COVID-19-associated moderate to severe ARDS compared with placebo? Study Design and Methods: A prospective phase 2 multicenter double-anonymized randomized placebo-controlled dosing trial was conducted at five sites across the United States with infusions of placebo, 10 mL of ExoFlo, or 15 mL of ExoFlo on days 1 and 4. Patients (N = 102) with COVID-19-associated moderate to severe ARDS were enrolled and randomized to treatment. Adverse events were documented throughout the study. The primary outcome measure was all-cause 60-day mortality rate. Secondary outcomes included time to death (overall mortality); the incidence of treatment-emergent serious adverse events; proportion of discharged patients at 7, 30, and 60 days; time to hospital discharge; and ventilation-free days. Results: No treatment-related adverse events were reported. Mortality (60-day) in the intention-to-treat population was reduced with 15 mL ExoFlo mixed with 85 mL normal saline (ExoFlo-15) compared with placebo (not significant, χ 2 , P = .1343). For the post hoc subgroup analyses, 60-day mortality was decreased with ExoFlo-15 compared with placebo (relative risk, 0.385; 95% CI, 0.159-0.931; P = .0340; n = 50). With ExoFlo-15, a relative risk of 0.423 (95% CI, 0.173-1.032; P = .0588; n = 24) was determined for participants aged 18 to 65 years with moderate to severe ARDS. Ventilation-free days improved with ExoFlo-15 (P = .0455; n = 50) for all participants aged 18 to 65 years. Interpretation: The 15 mL dose of ExoFlo was found to be safe in patients with severe or critical COVID-19-associated respiratory failure. In participants aged 18 to 65 years, the risk reduction in 60-day mortality was further improved from subjects of all ages in the intention-to-treat population after two doses of 15 mL of ExoFlo compared with placebo. Clinical Trial Registration: ClinicalTrials.gov; No.: NCT04493242; URL: www. Clinicaltrials: gov. Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: A. L. L. is CMO at Direct Biologics. J. T. R. is a PhD at Direct Biologics. S. Q. and V. S. are prior associate CMOs at Direct Biologics. None declared (S. S., D. J. P., T. I. M., B. P. W., J. J. W., M. A.). (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.) |
| Databáze: | MEDLINE |
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