Rheumatoid Arthritis Aggravated Clinical Trial
Official title:
"Phase Ib/IIa, Escalating Dose, Single Blind, Clinical Trial to Assess the Safety of the i.v Administration of Allogeneic Adipose-derived Mesenchymal Cells (eASCs) to Refractory Rheumatoid Arthritis (RA) Patients".
Phase Ib/IIa clinical trial of a new medicinal product of the somatic cell therapy class (eASCs). This study is designed as a multicenter, single blind, fixed dose escalation, with three treatment groups, controlled with placebo (randomization 3:1) whose target population are patients with rheumatoid arthritis refractory to at least two biologic.
Traditionally, RA has been treated with non-steroidal anti-inflammatory drugs,
glucocorticoids and non-biologics-DMARDs. Only non-biologics-DMARDs and, at a lesser extent,
glucocorticoids have shown to be able to prevent or interrupt the inflammatory and
destructive disease processes.
Mesenchymal stem cells (MSCs) are nonhematopoietic stromal cells that are able to
differentiate into mesenchymal tissues such as bone, cartilage, muscle, ligament, tendon, and
adipose. MSCs can be easily isolated from bone marrow or adipose tissue and rapidly expanded
in culture. MSCs have also been shown to have immuno-suppressive and healing capacities,
improve angiogenesis and prevent fibrosis. These properties could be used for novel
therapeutic applications in various disorders, including rheumatoid arthritis, osteoarthritis
(OA), genetic bone and cartilage disorders and bone metastasis. MSCs can potently modulate
immune responses, showing antiproliferative and anti-inflammatory capacities.
This study is a multicenter phase Ib/IIa, escalating dose, single blind clinical trial to
assess the safety of the intravenous administration of expanded allogeneic adipose-derived
mesenchymal stem cells (eASCs) to refractory rheumatoid arthritis (RA) patients.
The primary objective of the study is to determine the safety, feasibility and tolerance, and
to identify, if possible, the dose limiting toxicity (DLT) and the dose for future clinical
trials on efficacy of the intravenous infusion of allogeneic eASCs for patients suffering
rheumatoid arthritis (RA) under treatment with at least one non-biologic-Disease modifying
antirheumatoid drug (DMARD) who have previously failed to treatment with at least two
biologics. The secondary objective is to obtain information on the clinical and functional
effects of the intravenous infusion of allogeneic eASCs in patients with RA and to explore
pharmacodynamics parameters.
53 patients (i.e. patients having received at least one dose of study treatment) in three
different cohorts are planned to be included in this clinical trial. Expansion will start
after acute toxicity assessment of the first three patients of each cohort.
Dose and intervals for the trial consist of the following active groups: a) first cohort: 1
million cells/kg administered at days 1, 8 and 15; b) second cohort: 2 million cells / kg
administered at days 1, 8 and 15; c) third cohort: 4 million cells / kg administered at days
1, 8 and 15.
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