Date: 2014-04-30
Type of information: Initiation of development program
phase: 2
Announcement: initiation of a development program
Company: Tigenix (Belgium)
Product: Cx611
Action
mechanism: Cell therapy. Cx611 is a suspension of expanded allogeneic adult stem cells derived from human adipose (fat) tissue (expanded Adipose derived Stem Cells or 'eASCs') that is delivered through intravenous injection for the treatment of rheumatoid arthritis.
Disease: rheumatoid arthritis
Therapeutic area: Autoimmune diseases – Inflammatory diseases - Rheumatic diseases
Country:
Trial
details: The multicenter, randomized, double blind, placebo-controlled Phase IIa trial enrolled 53 patients with active refractory rheumatoid arthritis (mean time since diagnosis 15 years), who failed to respond to at least two biologics (mean previous treatment with 3 or more disease-modifying antirheumatic drugs and 3 or more biologics). The study design was based on a three-cohort dose-escalating protocol. For both the low and medium dose regimens 20 patients received active treatment versus 3 patients on placebo; for the high dose regimen 6 patients received active treatment versus 1 on placebo. Patients were dosed at day 1, 8, and 15 and were followed up monthly over a six-month period. Follow-up consisted of a detailed monthly workup of all patients measuring all pre-defined parameters. The aim was to evaluate the safety, tolerability and optimal dosing over the full 6 months of the trial, as well as exploring therapeutic activity.
Latest
news: * On June 30, 2014, TiGenix, the European leader in cell therapy, announced that it will develop Cx611 for patients suffering from early rheumatoid arthritis and for patients suffering from severe sepsis. In animal models, expanded Adipose-derived Stem Cells (eASCs) have been shown to down-regulate pro-inflammatory cytokines and up-regulate regulatory T cells which modulate the immune system. In a Phase IIa study of Cx611 in refractory rheumatoid arthritis completed and presented in 2013, the safety of the product was confirmed and signs of efficacy were encouraging (see below). Some patients treated with Cx611 entered remission after years of treatment with conventional and biological drugs. Assisted by a Steering Committee consisting of Professor Mark Genovese (Professor Immunology and Rheumatology, Stanford University, US), Professor Paul Emery (Professor of Rheumatology, University of Leeds, UK) and Professor José María Alvaro-Gracia (Head of the Biological Therapies Unit at the Hospital Universitario de La Princesa, Madrid, Spain), the principal investigator in the earlier Phase IIa study of Cx611 in refractory rheumatoid arthritis, TiGenix is working with a group of leading clinical experts, including Professor Luyten (Belgium), to complete the protocol for a randomised, double-blind, comparative Phase II study to test the efficacy of Cx611 in patients exhibiting substantial disease activity of rheumatoid arthritis despite treatment with methotrexate and corticosteroids, but unexposed to a biological drug. Recruitment for the proposed study could start in the third quarter of 2015 and TiGenix would expect final results to be available by the first half of 2017. * On April 22, 2013, TiGenix has announced positive 6-month safety data of its Phase IIa study of Cx611 in rheumatoid arthritis, as well as a first indication of therapeutic activity on standard outcome measures and biologic markers of inflammation for at least three months after dosing. This Phase IIa trial enrolled 53 patients with active refractory rheumatoid arthritis (mean time since diagnosis 15 years), who failed to respond to at least two biologics (mean previous treatment with 3 or more disease-modifying antirheumatic drugs and 3 or more biologics). The aim was to evaluate the safety, tolerability and optimal dosing over the full 6 months of the trial, as well as exploring therapeutic activity. Only one patient suffered serious adverse events that led to discontinuation of the treatment. All other side effects were mild and transient. Importantly, the first results show no signs of hematological side effects or thrombosis. Measured clinical activity scores were ACR20, ACR50, ACR70, EULAR response rates, and the disease activity score DAS28. To gain a first insight into the therapeutic activity, these parameters were evaluated every month for six months. The tables reflect cumulated results in percentages of all three active treatment arms at months 1 (M1), 2 (M2), 3 (M3), and "final visit" (FV). A more detailed analysis is currently ongoing. (ACR 20 means a 20% improvement in tender or swollen joint counts as well as 20% improvement in at least three of the following five criteria: patient assessment, physician assessment, erythrocyte sedimentation rate, pain scale and functional questionnaire. The ACR50 and ACR70 categories adhere to the same criteria, but for 50% and 70% improvement, respectively.EULAR, European League Against RheumatismDAS28, Disease Activity Score 28 joint count.) * On December 19, 2012, TiGenix has announced positive interim safety results of its Phase IIa study of Cx611 in rheumatoid arthritis (RA). The Company believes that this clinical trial can set the stage not only for the further development of Cx611 in RA, but also in a wide range of other autoimmune disorders. The interim results cover the first three months of the Phase IIa's six-month follow-up, and the data are still blinded. The primary endpoint of this study is safety, and the data collected so far support the good safety profile of all three doses of Cx611. Only two patients (4%) have suffered serious adverse events and only in one case (2%) it led to discontinuation of the treatment. All other side effects were mild and transient. The company is now looking forward to reporting the final results of the study at the end of April 2013. * On August 8, 2012, TiGenix has announced the completion of patient enrollment in the its phase IIa study of Cx611. "In addition to the primary endpoints of safety and optimal dosing, we expect this trial to yield a first indication of the duration of the efficacy of Cx611 in this very difficult patient population: the enrolled patients have previously failed to respond to at least two biologicals," said Eduardo Bravo, CEO of TiGenix. "In the trial patients are treated with three injections of Cx611. The six-month follow-up without further dosing should provide us with a truly meaningful result." * On April 17, 2012, TiGenix announced that upon review of the safety data of the first three patients of the third cohort of Cx611 it has received the go-ahead from the independent Safety Monitoring Board to recruit and dose the remaining patients of this cohort. The Phase IIa trial is based on a three-step dosefinding protocol, where each step starts with a safety review of the first three patients after 40 days of dosing. The company is on line with its expectations. With 6 months of follow-up, the current RA trial in 53 patients is expected to report the final results in the first half of 2013. * On February 1, 2012, TiGenix has announced that upon review of the safety data of the first three patients of the second cohort of Cx611 it has received the go-ahead from the independent Safety Monitoring Board to recruit and dose the remaining 20 patients of this cohort and to open the third and final cohort. * On October 25, 2011, TiGenix has received the go-ahead from the independent Safety Monitoring Board to move into the randomized stage of Cx611. This decision is based on the analysis of the safety data from patients treated in the study's first cohort.
