Bone Marrow Mesenchymal Stem Cell-Derived Extracellular Vesicle Infusion for the Treatment of Respiratory Failure From COVID-19

• Published in: Chest Vol. 164; no. 6; pp. 1444 - 1453
• Main Authors: Lightner, Amy L., Sengupta, Vikram, Qian, Sascha, Ransom, John T., Suzuki, Sam, Park, David J., Melson, Timothy I., Williams, Brian P., Walsh, James J., Awili, Mustafa
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.12.2023
• Subjects: bone marrow mesenchymal stem cell; COVID-19; efficacy; extracellular vesicle; safety; AE; ITT; BM-MSC; bone marrow mesenchymal stem cell; efficacy; ExoFlo-15; COVID-19; EV; TEAE; ExoFlo-10; VFD; safety; SAE; IRB; extracellular vesicle
• ISSN: 0012-3692; 1931-3543
• DOI: 10.1016/j.chest.2023.06.024

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. Do two doses of ExoFlo safely reduce mortality in COVID-19-associated moderate to severe ARDS compared with placebo? 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. 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, χ2, 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. 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. ClinicalTrials.gov; No.: NCT04493242; URL: www.clinicaltrials.gov. [Display omitted]