Cellular Immunotherapy for Septic Shock. A Phase I Clinical Trial

Am J Respir Crit Care Med. 2018 Feb 1;197(3):337-347. doi: 10.1164/rccm.201705-1006OC.

Abstract

Rationale: In septic animal models mesenchymal stem (stromal) cells (MSCs) modulate inflammation, enhance tissue repair and pathogen clearance, and reduce death.

Objectives: To conduct a phase I dose escalation trial of MSCs in septic shock with the primary objective of examining the safety and tolerability of MSCs.

Methods: We enrolled nine participants within 24 hours of admission to the ICU. A control cohort of 21 participants was enrolled before starting the MSC interventional cohort to characterize expected adverse events (AEs) and to serve as a comparator for the intervention cohort. Three separate MSC dose cohorts, with three participants per cohort, received a single intravenous dose of 0.3, 1.0, and 3.0 × 106 cells/kg. A prespecified safety plan monitored participants for the occurrence of AEs; cytokines were collected at prespecified time points.

Measurements and main results: Ages of participants in the interventional versus observational cohorts were median of 71 (range, 38-91) and 61 (range, 23-95). Acute Physiology and Chronic Health Evaluation scores were median of 25 (range, 11-28) and 26 (range, 17-32). MSC doses ranged from 19 to 250 million cells. There were no prespecified MSC infusion-associated or serious unexpected AEs, nor any safety or efficacy signals for the expected AEs or the measured cytokines between the interventional and observational cohorts.

Conclusions: The infusion of freshly cultured allogenic bone marrow-derived MSCs, up to a dose of 3 million cells/kg (250 million cells), into participants with septic shock seems safe. Clinical trial registered with www.clinicaltrials.gov (NCT02421484).

Keywords: allogeneic; bone marrow; mesenchymal stem cells; phase I clinical trial; septic shock.

Publication types

  • Clinical Trial, Phase I
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Allografts
  • Confidence Intervals
  • Female
  • Follow-Up Studies
  • Humans
  • Immunotherapy / methods*
  • Infusions, Intravenous
  • Male
  • Mesenchymal Stem Cell Transplantation / methods*
  • Middle Aged
  • Risk Assessment
  • Sex Factors
  • Shock, Septic / diagnosis
  • Shock, Septic / mortality
  • Shock, Septic / therapy*
  • Survival Rate
  • Treatment Outcome
  • Young Adult

Associated data

  • ClinicalTrials.gov/NCT02421484

Grant support