Clinical efficacy and safety of multipotent adult progenitor cells (invimestrocel) for acute respiratory distress syndrome (ARDS) caused by pneumonia: a randomized, open-label, standard therapy-controlled, phase 2 multicenter study (ONE-BRIDGE).

ABSTRACT

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a life-threatening inflammatory lung injury with high mortality; no approved medication exists. Efficacy and safety of bone marrow-derived, allogeneic, multipotent adult progenitor cells (invimestrocel) plus standard treatment in patients with ARDS caused by pneumonia was evaluated. METHODS: A randomized, open-label, standard therapy-controlled, phase 2 study (January 2019-September 2021) conducted in 29 centers in Japan. Patients with ARDS caused by pneumonia, with extensive early fibroproliferation on high-resolution computed tomography and low risk of systemic organ failure identified by an Acute Physiology and Chronic Health Evaluation (APACHE II) score were included. Patients were randomized 21 to receive a single intravenous infusion of 9.0 × 108 cells of invimestrocel (administered at a rate of up to 10 mL/min over 30-60 min by free flow) plus standard treatment (N = 20) or standard treatment (N = 10) consistent with the clinical practice guidelines of the Japanese Respiratory Society for the management of ARDS. Primary endpoint was ventilator-free days (VFDs) through day 28 after study treatment. Analysis of covariance was performed with treatment group, age, partial pressure arterial oxygen/fraction of inspired oxygen ratio, and APACHE II score as covariates. RESULTS: Median (interquartile range) number of VFDs was numerically higher in the invimestrocel group versus standard group (20.0 [0.0-24.0] vs 11.0 [0.0-14.0]) but was not statistically significantly different (least square [LS] means [95% confidence interval (CI)] invimestrocel group, 11.6 [6.9-16.3]; standard group, 6.2 [- 0.4 to 12.8]; LS mean difference [95% CI], 5.4 [- 1.9 to 12.8]; p = 0.1397). Ventilator weaning rate at day 28 was 65% (13/20) versus 30% (3/10), and mortality rate was 21% (4/19) versus 29% (2/7) at day 28 and 26% (5/19 patients) versus 43% (3/7 patients) at day 180, for the invimestrocel and standard groups, respectively. No allergic or serious adverse reactions were associated with invimestrocel. CONCLUSIONS: In Japanese patients with ARDS caused by pneumonia, invimestrocel plus standard treatment resulted in no significant difference in the number of VFDs but may result in improved survival compared with standard treatment. Invimestrocel was well tolerated. TRIAL REGISTRATION ClinicalTrials.gov, Identifier NCT03807804; January 8, 2019; https//clinicaltrials.gov/ct2/show/NCT03807804 .