Intravenous administration of expanded allogeneic adipose-derived mesenchymal stem cells in refractory rheumatoid arthritis (Cx611): results of a multicentre, dose escalation, randomised, single-blind, placebo-controlled phase Ib/IIa clinical trial

Objectives To evaluate the safety and tolerability of the intravenous administration of Cx611, a preparation of allogeneic expanded adipose-derived stem cells (eASCs), in refractory rheumatoid arthritis (RA) patients, as well as to obtain preliminary clinical efficacy data in this population. Methods Multicentre, dose escalation, randomised, single-blind (double-blind for efficacy), placebo controlled, phase Ib/IIa clinical trial. Patients with active refractory RA (failure to at least two biologicals) were randomised to receive three intravenous infusions (iv) of Cx611: 1 million/kg (cohort A), 2 million/kg (cohort B), 4 million/kg (cohort C), or placebo, on days 1, 8 and 15, and they were followed for therapy assessment for 24 weeks. Results Fifty-three patients were treated (20 in cohort A, 20 in cohort B, 6 in cohort C, and 7 in placebo group). A total of 141 adverse events (AEs) were reported. Seventeen patients from the group A (85%), 15 from the group B (75%), 6 from the group C (100%) and 4 from the placebo group (57%) experienced at least one AE. Eight AEs from 6 patients were grade 3 in intensity (severe), 5 in cohort A (lacunar infarction, diarrhoea, tendon rupture, rheumatoid nodule and arthritis), 2 in cohort B (sciatica and rheumatoid arthritis) and 1 in the placebo group (asthenia). Only one of the grade 3 AEs was serious (the lacunar infarction).ACR 20 responses for cohorts A, B, C and placebo were 45, 20, 33 and 29% respectively at month 1, and 25, 15, 17 and 0% respectively at month 3. Conclusion The intravenous infusion of Cx611 was in general well tolerated, without evidence of dose-related toxicity at the dose range and time period studied. In addition, a trend for clinical efficacy was observed. These data, in our opinion, justify further investigation of this innovative therapy in RA patients.