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.
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).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
278
120 million cells administered by intralesional injection.
24 mL saline solution by intralesional injection
Combine remission of perianal fistulising Crohn's
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.
Time frame: 24 weeks
Efficacy Assessment by week 24
* Clinical Remission (CR) defined as closure of all treated EO that were draining at baseline despite gentle finger compression, as clinically assessed * Response defined as closure of at least 50% of all treated EO that were draining at baseline, as clinically assessed * Time to Clinical Remission (time from treatment start to 1st visit with closure of all treated EO as described above) * Time to Response (time from treatment start to 1st visit with closure of at least 50% of all treated EO as described above) * Relapse defined, in patients with CR at previous visit, as reopening of any of the treated EO with active drainage, or the development of a perianal collection \> 2 cm of the treated perianal fistulas confirmed by centrally blinded MRI * Time to Relapse in patients with CR (time from CR to 1st visit with reopening of any of the treated EO as described above) * Severity of the perianal CD, assessed with the PDAI * QoL assessed by IBDQ * CDAI score * Van Assche
Time frame: 24 weeks
Efficacy Assessment by week 52
* Combined Remission of perianal fistulising Crohn's disease at week 52 (as defined for week 24) * Clinical Remission defined as the closure of all treated external openings that were draining at baseline despite gentle finger compression, as clinically assessed at week 52 * Response defined as closure of at least 50% of all treated external openings that were draining at baseline, as clinically assessed at week 52 * Time to Combined Remission by week 52 (as defined for week 24) * Time to Clinical Remission by week 52 (as defined for week 24) * Time to Response by week 52 (as defined for week 24) * Relapse by week 52 in patients with Combined Remission at week 24 (as defined for week 24) * Time to Relapse by week 52 in patients with Combined Remission at week 24 (as defined for week 24) * Severity of the perianal Crohn's disease up to week 52 assessed PDAI * QoL up to week 52 by the IBDQ * CDAI score up to week 52 * Van Assche score up to week 52
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Univ.-Klinik Innsbruck
Innsbruck, Austria
Krankenhaus
Saint Veit/Glan, Austria
Medizinische Universität
Vienna, Austria
Hospital Oost-Limburg
Genk, Belgium
Gent University Hospital
Ghent, Belgium
Leuven University Hospital
Leuven, Belgium
Hospital Hartziekenhuis
Roeselare, Belgium
CHU d'Amiens
Amiens, France
CHU de Bordeaux
Bordeaux, France
CHU de Caen
Caen, France
...and 42 more locations
Time frame: 52 weeks
Efficacy Assessment by week 104
* Clinical Remission of perianal fistulising Crohn's disease defined as the clinical assessment of closure of all treated external openings that were draining at baseline despite gentle finger compression at week 104 * Relapse by week 104 in patients with Combined Remission at week 52, defined as reopening of any of the treated external openings with active drainage as clinically assessed * Time to Relapse by week 104 in patients with Combined Remission at week 52 (defined as time from Combined Remission to first visit with reopening of any of the treated external openings with active drainage as clinically assessed) * Severity of the perianal Crohn's disease, assessed with the Perianal Disease Activity Index (PDAI) up to week 104 * Quality of Life (QoL) assessed by the Inflammatory Bowel Disease Questionnaire (IBDQ) up to week 104 * CDAI score up to week 104
Time frame: 104 Weeks
Safety analysis throughout the study:
* Adverse events including: Treatment emergent Adverse Events (TEAEs), TEAEs related to study treatment, Treatment emergent Serious Adverse Events (TESAEs), TESAEs related to study treatment, TEAEs leading to study withdrawal, adverse events related to surgical procedure(s) to provide study treatment, deaths Only SAEs will be reported during the 2nd follow-up period between week 52 and week 104. * Physical examination * Vital signs * Laboratory tests (biochemistry, haematology, urinalysis)
Time frame: week 24, 52 and 104