TiGenix

Safety and tolerability of Cx611 confirmed in Phase I sepsis challenge trial - Seite 2

For more information:

Richard Simpson
Senior Consultant, Comfi sprl
T: [phone]
[e-mail]

About Cx611

Cx611 is an intravenously-administered product of allogeneic expanded adipose-derived stem cells (eASCs). TiGenix is currently developing Cx611 for patients with early rheumatoid arthritis and for patients with severe sepsis. For the first of these two indications, in 2013 TiGenix reported positive 6-month safety data from its Phase IIa study of Cx611 in refractory rheumatoid arthritis, as well as a first indication of therapeutic activity using standard outcome measures and biologic markers of inflammation for at least three months after dosing. The multicentre, randomised, double-blind, placebo-controlled Phase IIa trial enrolled 53 patients with active refractory rheumatoid arthritis (mean time since diagnosis 15 years), under treatment with at least one non-biologic disease-modifying anti-rheumatic drug (DMARD), who failed to respond to at least two biologic drugs (mean previous treatment: 3 or more DMARDs and 3 or more biologic drugs). 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 Days 1, 8, and 15 and were followed up monthly over a six-month period. Follow-up consisted of a detailed monthly work-up 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. Only one patient suffered serious adverse events that led to a discontinuation of treatment. All other side effects were mild and transient indicating that eASCs are well tolerated and associated with an overall acceptable safety profile. Measured clinical activity scores were ACR20¹, ACR50¹, ACR70¹, EULAR² response rates, and the disease activity score, DAS28³. To gain a first insight into therapeutic activity, these parameters were evaluated every month for six months. Patients receiving Cx611 had higher ACR scores, a better EULAR response, and higher DAS28 scores than patients receiving placebo over three months, and a sustained benefit over six months. The Company is currently working with clinical experts to complete a 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 fourth quarter of 2015 and TiGenix would expect final results to be available by the end of 2017.