PMID- 27269294
OWN - NLM
STAT- MEDLINE
DCOM- 20170530
LR  - 20220408
IS  - 1468-2060 (Electronic)
IS  - 0003-4967 (Linking)
VI  - 76
IP  - 1
DP  - 2017 Jan
TI  - 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.
PG  - 196-202
LID - 10.1136/annrheumdis-2015-208918 [doi]
AB  - 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.
CI  - Published by the BMJ Publishing Group Limited. For permission to use (where not 
      already granted under a licence) please go to 
      http://www.bmj.com/company/products-services/rights-and-licensing/.
FAU - Alvaro-Gracia, Jose M
AU  - Alvaro-Gracia JM
AD  - Hospital Universitario de La Princesa, IIS-IP, Madrid, Spain.
FAU - Jover, Juan A
AU  - Jover JA
AD  - Hospital Universitario Clinico San Carlos de Madrid, Madrid, Spain.
FAU - Garcia-Vicuna, Rosario
AU  - Garcia-Vicuna R
AD  - Hospital Universitario de La Princesa, IIS-IP, Madrid, Spain.
FAU - Carreno, Luis
AU  - Carreno L
AD  - Hospital General Universitario Gregorio Maranon, Madrid, Spain.
FAU - Alonso, Alberto
AU  - Alonso A
AD  - Hospital de Cruces, Bilbao, Spain.
FAU - Marsal, Sara
AU  - Marsal S
AD  - Hospital Vall d'Hebron, Barcelona, Spain.
FAU - Blanco, Francisco
AU  - Blanco F
AD  - INIBIC-Complejo Hospitalario Universitario A Coruna, A Coruna, Spain.
FAU - Martinez-Taboada, Victor M
AU  - Martinez-Taboada VM
AD  - Hospital Universitario Marques de Valdecilla, Santander, Spain.
AD  - Facultad de Medicina, Universidad de Cantabria, Santander, Spain.
FAU - Taylor, Peter
AU  - Taylor P
AD  - Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK.
FAU - Martin-Martin, Cristina
AU  - Martin-Martin C
AD  - IRYCIS, Hospital Universitario Ramon y Cajal, Madrid, Spain.
FAU - DelaRosa, Olga
AU  - DelaRosa O
AD  - TiGenix, Madrid, Spain.
FAU - Tagarro, Ignacio
AU  - Tagarro I
AD  - TiGenix, Madrid, Spain.
FAU - Diaz-Gonzalez, Federico
AU  - Diaz-Gonzalez F
AD  - Department of Medicine, Universidad de La Laguna, La Laguna, Spain.
AD  - Complejo Hospitalario Universitario de Canarias, Tenerife, Spain.
LA  - eng
SI  - ClinicalTrials.gov/NCT01663116
PT  - Clinical Trial, Phase I
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
DEP - 20160607
PL  - England
TA  - Ann Rheum Dis
JT  - Annals of the rheumatic diseases
JID - 0372355
RN  - 0 (Biomarkers)
RN  - 9007-41-4 (C-Reactive Protein)
SB  - IM
MH  - Adipose Tissue/cytology
MH  - Adult
MH  - Aged
MH  - Arthritis, Rheumatoid/immunology/*therapy
MH  - Biomarkers/blood
MH  - C-Reactive Protein/metabolism
MH  - Female
MH  - Humans
MH  - Infusions, Intravenous
MH  - Male
MH  - Mesenchymal Stem Cell Transplantation/adverse effects/*methods
MH  - Middle Aged
MH  - Severity of Illness Index
MH  - Single-Blind Method
MH  - Treatment Outcome
OTO - NOTNLM
OT  - *B cells
OT  - *Rheumatoid Arthritis
OT  - *T Cells
OT  - *Treatment
EDAT- 2016/06/09 06:00
MHDA- 2017/05/31 06:00
CRDT- 2016/06/09 06:00
PHST- 2015/11/18 00:00 [received]
PHST- 2016/05/17 00:00 [accepted]
PHST- 2016/06/09 06:00 [pubmed]
PHST- 2017/05/31 06:00 [medline]
PHST- 2016/06/09 06:00 [entrez]
AID - annrheumdis-2015-208918 [pii]
AID - 10.1136/annrheumdis-2015-208918 [doi]
PST - ppublish
SO  - Ann Rheum Dis. 2017 Jan;76(1):196-202. doi: 10.1136/annrheumdis-2015-208918. Epub 
      2016 Jun 7.