A Phase III, Randomized, Double Blind, Parallel Group, Placebo Controlled, Multicentre Study to Assess Efficacy and Safety of Expanded Allogeneic Adipose-derived Stem Cells (eASCs) for the Treatment of Perianal Fistulising Crohn's Disease Over a Period of 24 Weeks and an Extended Follow-up Period up to 104 Weeks.
Overview
- Phase
- Phase 3
- Intervention
- Not specified
- Conditions
- Crohn's Disease
- Sponsor
- Tigenix S.A.U.
- Enrollment
- 278
- Locations
- 52
- Primary Endpoint
- Combine remission of perianal fistulising Crohn's
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
The current multicentre phase III study is proposed to confirm in an add-on therapy design compared to a placebo-control group, the efficacy of adipose-derived stem cells (eASCs) from healthy donors for the treatment of complex anal fistulas in patients with Crohn's disease over a 24-week period and an extended follow-up period up to 104 weeks.
Detailed Description
The current multicentre phase III study is proposed to confirm in an add-on therapy design compared to a placebo-control group, the efficacy of adipose-derived stem cells (eASCs) from healthy donors for the treatment of complex anal fistulas in patients with Crohn's disease over a 24-week period and an extended follow-up period up to 104 weeks. Subject with perianal fistulising Crohn's disease will be treated with Cx601, suspension of eASCs, at a dose of 120 million cells administered by intralesional injection. The treatment of complex perianal fistulas by local application of eASCs intends to improve significantly the local conditions with very few inconveniences (ambulatory procedure) and minimal risk of possible complications (anal incontinence). Therefore, this is a new therapeutic resource that is expected to be safe and efficacious as well as is expected to improve the quality of life of the patients in this highly debilitating and chronic condition. This treatment would prevent one of the main causes of anal incontinence, would diminish recurrence of the fistula disease and would reduce drastically the significant disorders provoked by the standard fistula surgery in the patients. Indeed, patients can be discharged according to the "One Day Surgical" procedures (major ambulatory surgery).
Investigators
Eligibility Criteria
Inclusion Criteria
- •The reference population will consist of patients with perianal fistulising Crohn´s disease refractory to at least one of the following treatments: antibiotics, immunosuppressants or anti-tumor necrosis factor (TNF). Naïve patients are excluded, and those patients refractory to antibiotics will represent less than 25% of the total recruited patients.
- •All of them must comply with the following inclusion criteria:
- •Signed informed consent.
- •Patients with Crohn's Disease (CD) diagnosed at least 6 months earlier in accordance with accepted clinical, endoscopic, histological and/or radiologic criteria.
- •Presence of complex perianal fistulas with a maximum of 2 fistulas (internal openings) and a maximum of 3 external openings, assessed by clinical assessment and MRI. Fistula must have been draining for at least 6 weeks prior to the inclusion. A complex perianal fistula is defined as a fistula that met one or more of the following criteria during its evolution:
- •High inter-sphincteric, trans-sphincteric, extra-sphincteric or supra-sphincteric.
- •Presence of ≥ 2 external openings (tracts).
- •Associated collections
- •Non-active or mildly active luminal CD defined by a CDAI ≤
- •Patients of either sex aged 18 years or older
Exclusion Criteria
- •Presence of dominant luminal active Crohn's disease requiring immediate therapy.
- •Concomitant rectovaginal fistulas
- •Patient naïve to specific treatment for perianal fistulising Crohn's disease including antibiotics
- •Presence of an abscess or collections \> 2 cm, unless resolved in the preparation procedure (week -3 to day 0).
- •Presence of \> 2 fistular lesions.
- •Presence of \> 3 external openings.
- •Rectal and/or anal stenosis and / or active proctitis, if this means a limitation for any surgical procedure.
- •Patient who underwent surgery for the fistula other than drainage or seton placement.
- •Patient with diverting stomas
- •Patient with ongoing steroid treatment or treated with steroids in the last 4 weeks
Outcomes
Primary Outcomes
Combine remission of perianal fistulising Crohn's
Time Frame: 24 weeks
Combined Remission of perianal fistulising Crohn's disease defined as the clinical assessment of closure of all treated external openings (EO) that were draining at baseline despite gentle finger compression at week 24, and absence of collections \> 2 cm of the treated perianal fistulas confirmed by centrally blinded MRI assessment by week 24.
Secondary Outcomes
- Efficacy Assessment by week 24(24 weeks)
- Efficacy Assessment by week 104(104 Weeks)
- Safety analysis throughout the study:(week 24, 52 and 104)
- Efficacy Assessment by week 52(52 weeks)