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.
OBJECTIVE
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.


BACKGROUND
EudraCT: 2010-021602-37; NCT01663116; Results.
Hospital Universitario de La Princesa, IIS-IP, Madrid, Spain.
Jose M
JM
Álvaro-Gracia
Hospital Universitario Clínico San Carlos de Madrid, Madrid, Spain.
Juan A
JA
Jover
Hospital Universitario de La Princesa, IIS-IP, Madrid, Spain.
Rosario
R
García-Vicuña
Hospital General Universitario Gregorio Marañón, Madrid, Spain.
Luis
L
Carreño
Hospital de Cruces, Bilbao, Spain.
Alberto
A
Alonso
Hospital Vall d'Hebron, Barcelona, Spain.
Sara
S
Marsal
INIBIC-Complejo Hospitalario Universitario A Coruña, A Coruña, Spain.
Francisco
F
Blanco
Hospital Universitario Marqués de Valdecilla, Santander, Spain.|Facultad de Medicina, Universidad de Cantabria, Santander, Spain.
Victor M
VM
Martínez-Taboada
Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK.
Peter
P
Taylor
IRYCIS, Hospital Universitario Ramón y Cajal, Madrid, Spain.
Cristina
C
Martín-Martín
TiGenix, Madrid, Spain.
Olga
O
DelaRosa
TiGenix, Madrid, Spain.
Ignacio
I
Tagarro
Department of Medicine, Universidad de La Laguna, La Laguna, Spain.|Complejo Hospitalario Universitario de Canarias, Tenerife, Spain.
Federico
F
Díaz-González
D000273:Adipose Tissue / Q000166:cytology; D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000628:therapy*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D008875:Middle Aged; D012720:Severity of Illness Index; D016037:Single-Blind Method; D016896:Treatment Outcome
D015415:Biomarkers; D002097:C-Reactive Protein
B cells; Rheumatoid Arthritis; T Cells; Treatment