Dataset Information

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.

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. EudraCT Number 2017-000584-33.

SUBMITTER: Gorman E

PROVIDER: S-EPMC9099345 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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.

Gorman Ellen E Shankar-Hari Manu M Hopkins Phil P Tunnicliffe William S WS Perkins Gavin D GD Silversides Jonathan J McGuigan Peter P Jackson Colette C Boyle Roisin R McFerran Jamie J McDowell Cliona C Campbell Christina C McFarland Margaret M Smythe Jon J Thompson Jacqui J Williams Barry B Curley Gerard G Laffey John G JG Clarke Mike M McAuley Daniel F DF O'Kane Cecilia C

Trials 20220513 1

<h4>Background</h4>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.<h4>Methods</h4>Phase 1 is a multicentre open-label dose-escalation pilot trial. Patients will receive a single infusion of REALIST ...[more]

PMID: 35562778

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Dataset Information

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.

Background

Methods

Discussion

Trial registration

Publications

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.

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