Jose M Álvaro-Gracia1, Juan A Jover2, Rosario García-Vicuña1, Luis Carreño3, Alberto Alonso4, Sara Marsal5, Francisco Blanco6, Victor M Martínez-Taboada7,8, Peter Taylor9, Cristina Martín-Martín10, Olga DelaRosa11, Ignacio Tagarro11, Federico Díaz-González12,13. 1. Hospital Universitario de La Princesa, IIS-IP, Madrid, Spain. 2. Hospital Universitario Clínico San Carlos de Madrid, Madrid, Spain. 3. Hospital General Universitario Gregorio Marañón, Madrid, Spain. 4. Hospital de Cruces, Bilbao, Spain. 5. Hospital Vall d'Hebron, Barcelona, Spain. 6. INIBIC-Complejo Hospitalario Universitario A Coruña, A Coruña, Spain. 7. Hospital Universitario Marqués de Valdecilla, Santander, Spain. 8. Facultad de Medicina, Universidad de Cantabria, Santander, Spain. 9. Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK. 10. IRYCIS, Hospital Universitario Ramón y Cajal, Madrid, Spain. 11. TiGenix, Madrid, Spain. 12. Department of Medicine, Universidad de La Laguna, La Laguna, Spain. 13. Complejo Hospitalario Universitario de Canarias, Tenerife, Spain.
Abstract
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. 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/.
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. 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/.
Entities:
Keywords:
B cells; Rheumatoid Arthritis; T Cells; Treatment
Authors: Alexandra M Roch; Thomas K Maatman; Todd G Cook; Howard H Wu; Stephanie Merfeld-Clauss; Dmitry O Traktuev; Keith L March; Nicholas J Zyromski Journal: J Gastrointest Surg Date: 2019-11-19 Impact factor: 3.452