Objectives To evaluate the safety and tolerability of the intravenous administration of Cx611, a preparation of allogeneic expanded adipose-derived stem cells (eASCs), in patients with refractory rheumatoid arthritis (RA), as well as to obtain preliminary clinical efficacy data in this population.
Methods It is a 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 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 RA) and 1 in the placebo group (asthenia). Only one of the grade 3 AEs was serious (the lacunar infarction). American College of Rheumatology 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.
Conclusions 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 patients with RA.
Trial registration numbers EudraCT: 2010-021602-37; NCT01663116; Results.
- Rheumatoid Arthritis
- B cells
- T Cells
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Handling editor Tore K Kvien
Collaborators Additional list of investigators Javier Ballina, Hospital Central Asturias, Oviedo. Ricardo Blanco Alonso, Hospital Marqués de Valdecilla, Santander. Sagrario Bustabad, Complejo Hospitalario Universitario de Canarias, Tenerife. Eugenio Chamizo, Hospital General de Mérida. Antonio Fernández-Nebro, Hospital Carlos Haya de Málaga. José Luis Marenco, Hospital Nuestra Sra. Valme, Sevilla. Emilio Martín-Mola, Hospital La Paz, Madrid. Federico Navarro, Hospital Virgen Macarena, Sevilla. Arturo Rodríguez, Hospital Santa Creu i Sant Pau, Barcelona. José Andrés Román-Ivorra, Hospital La Fe, Valencia. Raimon Sanmartí, Hospital Clinic i Provincial, Barcelona. Jesús Tornero, Hospital de Guadalajara.
Contributors JMA-G, VMM-T, PT, FD-G and ODR were involved in study design, data analysis and in drafting and reviewing the manuscript. IT was involved in data analysis, and in drafting and reviewing the manuscript. JAJ, RG-V, LC, AA, SM and FB were involved in patient recruitment, treatment and follow-up, and in reviewing the manuscript. CMM was involved in anti-HLA antibodies detection and manuscript review.
Funding This work was funded by TiGenix and the European Union's Seventh Programme for research, technological development and demonstration under grant agreement no 279174 to TiGenix.
Competing interests JMA-G, VMM-T, PT and FD-G received advisory fees from Tigenix. ODR and IT are employees of Tigenix.
Patient consent Obtained.
Ethics approval Ethics committee at Hospital de la Princesa, Madrid, and others.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement Data are available upon request to the corresponding author.