Repair of acute respiratory distress syndrome by stromal cell administration (REALIST): a structured study protocol for an open-label dose-escalation phase 1 trial followed by a randomised, triple-blind, allocation concealed, placebo-controlled phase 2 trial

Ellen Gorman, Manu Shankar-Hari, Phil Hopkins, William S. Tunnicliffe, Gavin D. Perkins, Jonathan Silversides, Peter McGuigan, Colette Jackson, Roisin Boyle, Jamie McFerran, Cliona McDowell, Christina Campbell, Margaret McFarland, Jon Smythe, Jacqui Thompson, Barry Williams, Gerard Curley, John G. Laffey, Mike Clarke, Daniel F. McAuleyCecilia O’Kane*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Mesenchymal stromal cells (MSCs) may be of benefit in ARDS due to immunomodulatory and reparative properties. This trial investigates a novel CD362 enriched umbilical cord derived MSC product (REALIST ORBCEL-C), produced to Good Manufacturing Practice standards, in patients with moderate to severe ARDS due to COVID-19 and ARDS due to other causes. Methods: Phase 1 is a multicentre open-label dose-escalation pilot trial. Patients will receive a single infusion of REALIST ORBCEL-C (100 × 106 cells, 200 × 106 cells or 400 × 106 cells) in a 3 + 3 design. Phase 2 is a multicentre randomised, triple blind, allocation concealed placebo-controlled trial. Two cohorts of patients, with ARDS due to COVID-19 or ARDS due to other causes, will be recruited and randomised 1:1 to receive either a single infusion of REALIST ORBCEL-C (400 × 106 cells or maximal tolerated dose in phase 1) or placebo. Planned recruitment to each cohort is 60 patients. The primary safety outcome is the incidence of serious adverse events. The primary efficacy outcome is oxygenation index at day 7. The trial will be reported according to the Consolidated Standards for Reporting Trials (CONSORT 2010) statement. Discussion: The development and manufacture of an advanced therapy medicinal product to Good Manufacturing Practice standards within NHS infrastructure are discussed, including challenges encountered during the early stages of trial set up. The rationale to include a separate cohort of patients with ARDS due to COVID-19 in phase 2 of the trial is outlined. Trial registration: ClinicalTrials.gov NCT03042143. Registered on 3 February 2017.

Original languageEnglish
Article number401
JournalTrials
Volume23
Issue number1
Early online date13 May 2022
DOIs
Publication statusPublished - Dec 2022

Keywords / Materials (for Non-textual outputs)

  • Acute respiratory distress syndrome
  • Clinical trial
  • COVID-19
  • Mesenchymal stem cells
  • Mesenchymal stromal cells
  • MSCs
  • Protocol

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