The safety and efficacy of stem cells for the treatment of severe community-acquired bacterial pneumonia: A randomized clinical trial.

ABSTRACT

PURPOSE: Evaluate the safety profile of expanded allogeneic adipose-derived mesenchymal stem cell (eASC) for the treatment of severe community-acquired bacterial pneumonia (CABP). MATERIALS AND METHODS: Randomized, multicenter, double-blind, placebo-controlled, phase 1b/2a trial. Patients with severe CABP were enrolled to receive intravenous infusions of Cx611 or placebo. The primary objective was safety including hypersensitivity reactions, thromboembolic events, and immunological responses to Cx611. The secondary endpoints included the clinical cure rate, ventilation-free days, and overall survival (Day 90). RESULTS: Eighty-three patients were randomized and received infusions (Cx611 n = 42]; placebo n = 41]. The mean age was similar (Cx611 61.1 [11.2] years; placebo 63.4 [10.4] years). The number of AEs and treatment-emergent AEs were similar (243; 184 and 2; 1) in Cx611 and placebo respectively. Hypersensitivity reactions or thromboembolic events were similar (Cx611 n = 9; placebo n = 12). Each study arm had similar anti-HLA antibody/DSA levels at Day 90. The clinical cure rate (Cx611 86.7%; placebo 93.8%), mean number of ventilator-free days (Cx611 12.2 [10.29] days; placebo 15.4 [10.75] days), and overall survival (Cx611 71.5%; placebo 77.0%) did not differ between study arms. CONCLUSION: Cx611 was well tolerated in severe CABP. These data provide insights for future stem cell clinical study designs, endpoints and sample size calculation. TRIAL REGISTRATION NCT03158727 (retrospectively registered May 09, 2017). Full study protocol https//clinicaltrials.gov/ProvidedDocs/27/NCT03158727/Prot_000.pdf.