Clinical Trials

Date: 2017-06-13

Type of information: Initiation of the trial

phase: 3

Announcement: initiation of the trial

Company: Tigenix (Belgium)

Product: Cx601 (adipose derived allogeneic stem cell therapy)

Action mechanism:

• Cell therapy. Cx601 is a suspension of expanded allogeneic adult stem cell (eASCs) product derived from human adipose (fat) tissue (expanded Adipose derived Stem Cells or eASCs) that is delivered locally in the fistula through intra-lesional injection. Cx601 is currently in Phase III of clinical development for the treatment of complex perianal fistulas in patients with Crohn's disease.
• Cx601 has been licensed to Takeda for the exclusive development and commercialization outside the US.

Disease: complex perianal fistulas in patients with Crohn's disease 

Therapeutic area: Autoimmune diseases - Inflammatory diseases - Digestive diseases

Country: USA

Trial details:

• The global pivotal Phase III trial is a randomized, double-blind, placebo-controlled study designed to confirm the efficacy and safety of a single administration of Cx601 for the treatment of complex perianal fistulas in Crohn's disease patients. The trial design is similar to the European Phase III ADMIRE-CD trial for Cx601 with an identical primary endpoint. In January 2017, the U.S. Food and Drug Administration (FDA) agreed to the design of the protocol for the global Phase III trial, and confirmed that a future U.S Biologics License Application (BLA) could be filed based on the study results at week 24, instead of week 52, from a broader patient population than the initial Special Protocol Assessment (SPA) formally endorsed in August 2015. With these adjustments, the trial should benefit from an expedited recruitment process, leading to shorter timelines, an earlier filing, and the possibility of an earlier approval in the U.S.

Latest news:

• • On June 13, 2017, TiGenix announced that it has hosted its first European investigator meeting, which formally launches the global pivotal phase III clinical trial for Cx601 for the treatment of complex perianal fistulas in patients with Crohn's disease. Similar investigator meetings are planned to take place in Europe (EU), Israel, the United States and Canada from the fourth quarter of 2017. The global trial is designed to support a future regulatory filing for Cx601 in the U.S. The first investigator meeting, held on June 8 and June 9 in Rome, Italy, brought together more than 60 leading gastroenterologists, colorectal surgeons and study co-ordinators from 30 confirmed clinical trial sites across Belgium, Czech Republic, Italy, Poland and Spain. Presentations were given by national and regional study co-ordinators, including the principal EU/Israel gastroenterologist study co-ordinator, Professor Julián Panés, Head of the Inflammatory Bowel Disease Unit at the Hospital Clinic of Barcelona (Spain) and President of the European Crohn's and Colitis Organization (ECCO), and the EU/Israel surgeon study coordinator, Dr. Damián García Olmo, Chief of the Department of Surgery at Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid.
• • On March 7, 2017, TiGenix announced that it has received positive feedback from the FDA on an improved protocol for its global Phase III trial for the treatment of complex perianal fistulas in Crohn's disease patients. On August 2015, TiGenix received the FDA endorsement of a Special Protocol Assessment (SPA) for a pivotal Phase III study for Biologics License Application (BLA) in the U.S (see below). Since the granting of the SPA, further confirmatory positive results have been obtained from the European Phase III study of Cx601 (ADMIRE-CD). Subsequently, TiGenix submitted a Marketing Authorization Application to the European Medicines Agency in March 2016. Following the publication of this additional data, TiGenix submitted a series of technical improvements to be considered by the FDA regarding the previously endorsed protocol.
• Based on the minutes from a meeting with the FDA on January 19, 2017, the Agency has agreed to an improved protocol for the global Phase III trial of Cx601. With these current amendments, the FDA has agreed that the BLA could be filed based on the efficacy and safety follow-up of patients assessed at week 24, instead of week 52. Furthermore, the FDA has agreed to accept fewer patients than originally planned in the study, and has endorsed a broader target population that will ultimately facilitate the recruitment process. With these adjustments, the study will benefit from an expedited recruitment process that should lead to shorter timelines, an earlier filing, and the possibility of an earlier approval in the U.S. As a result of these modifications, the trial design is even more similar to the European ADMIRE-CD than it was before. The trial for the U.S. registration of Cx601 is expected to begin in the first half of 2017. In parallel, TiGenix is exploring further expedited pathways to accelerate the submission and review process for its future BLA.
• • On August 7, 2015, TiGenix announced that it has reached an agreement with the FDA on a Special Protocol Assessment (SPA) for its Phase III registration trial of Cx601 in the U.S. for the treatment of complex perianal fistulas in Crohn's disease patients. The agreed pivotal trial is a randomised, double-blind, parallel group, placebo-controlled and multicentre study in complex perianal fistulas in Crohn's disease patients. The study will enroll approximately 224 patients to assess the efficacy and safety of Cx601 24 and 52 weeks after a single dose administration of the product. The SPA describes the primary endpoint as combined remission, defined as clinical assessment by week 24 of closure of all treated external openings draining at baseline despite gentle compression, and absence of collections > 2cm confirmed by MRI. This primary endpoint is in line with the one for the European Phase III trial, which results are expected later this quarter. The company expects to complete the process of manufacturing technology transfer to its U.S.-based CMO, Lonza, and thereafter will start its Phase III trial of Cx601 in the U.S. in the second half of 2016.
• • On December 22, 2014, TiGenix announced that it has submitted to the FDA the required documentation for a Special Protocol Assessment (SPA) of its pivotal Phase III trial design for Cx601 in the treatment of complex perianal fistulas in patients with Crohn's disease in the United States.  The planned US study design is similar to the ongoing Phase III trial in Europe, whose results are expected in the third quarter of 2015. The US trial design protocol incorporates guidance both from the FDA and from the Company's US Scientific Advisory Board of six leading North American clinical experts in gastroenterology and inflammatory bowel disease.
• The randomised, double-blind, placebo-controlled Phase III trial in the US is designed to confirm the efficacy and safety of Cx601 in the treatment of complex perianal fistulas in Crohn's disease patients. It will enrol approximately 180 patients and its primary endpoint will be the remission of fistulous disease, defined as 100% healing of the tracts. The first complete analysis of results will be at 24 weeks, with a follow-up analysis at 52 weeks post-treatment. As discussed with the FDA, TiGenix plans to use data from both the Phase III trial in Europe and from this Phase III trial in the US as the basis for its eventual submission of a Biologics License Application (BLA). On completion of the SPA review process, and of the technology transfer of its cell manufacturing process to a contract manufacturing organisation (CMO) in the US, TiGenix will submit its investigational new drug application (IND) for this Phase III study to the FDA.

Is general: Yes