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

Abstract

Community-acquired bacterial pneumonia; Intensive care unit; Mesenchymal stem cells

Neumonía bacteriana adquirida en la comunidad; Unidad de cuidados intensivos; Células madre mesenquimales

Pneumònia bacteriana adquirida a la comunitat; Unitat de cures intensives; Cèl·lules mare mesenquimal

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.

This study was supported by a grant from European Union's Horizon 2020 Research and Innovation Program (agreement number 681031); funding from this grant covered approximately one-third of the total estimated costs of the SEPCELL trial. The study sponsor is TiGenix SAU (a wholly-owned subsidiary of Takeda Pharmaceuticals) who funded approximately two-thirds of the total estimated trial costs. The funding from TiGenix SAU/Takeda Pharmaceuticals covered costs associated with (but not limited to) appointing the contract research organization, the manufacturing and shipping of Cx611, rental and shipping of cryofreezers for storage of Cx611 at study sites, internal personnel costs for all departments involved in the SEPCELL trial, regulatory submissions, and interactions.