Clinical trial NCT06636032: Dose Escalation of Allogeneic Adipose Derived Stroma/Stem Cells for the Treatment of Crohn's Fistula
Official title: Dose Escalation of Allogeneic Adipose Derived Stroma/Stem Cells for the Treatment of Crohn's Fistula:a Phase I/II Clinical Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Crohn Disease
Keywords: Crohn's disease
perianal fistula
regenerative medicine
immunomodulation
allogeneic adipose-derived stem cell
Lead sponsor: University Hospital, Toulouse
Sponsor class: OTHER
First posted: 2024-10-10
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Perianal fistulas are in the forefront (42 to 72, 4%) of morbid complication of Crohn's disease, affecting nearly one- third of patients and complicating abscesses in 35-48% of cases. The current treatment is based on the combination of drainage (proctologic and surgical), and biologics techniques, but the failure rate varies from 30 to 80%. Actually, innovative cell therapy procedures are validated by Cell-Easy with the use of allogenic mesenchymal stem cells for the immunomodulatory, anti-inflammatory, angiogenic and trophic properties (CellReady®) and represent a promising option in the treatment of perianal fistulas associated with Crohn's disease. This phase I/II study is designed to evaluate the treatment of complex perianal fistulas associated with Crohn's disease, after failure of conventional treatment by injection of allogeneic cultured adipose-derived stromal cell (AdMSC) into the fistula.

Detailed description: The injection of adipose stromal cells is currently evaluated in clinical studies for repair-damaged tissues in various diseases (limb ischemia, osteoarthritis, systemic slerosis...). Immunoregulatory and anti-inflammatory properties of AdMSC's are responsible for accelerating healing and represents an innovative approach to treat perianal fistulas associated with Crohn's disease.

This phase I/II study is designed to evaluate the treatment of complex perianal fistulas associated with Crohn's disease, after failure of conventional treatment by injection of AdMSC (CellReady®) into the fistula.

Different doses of AdMSC will be tested for a dose escalation (5.10\*7 and 10.10\*7 cells) and injected in the in the wall of the fistula.

Eligibility criteria: Inclusion Criteria:

* Patients over 18 years old,
* Patients who signed the informed consent,
* Patient affiliated to a social security system,
* Controlled luminal Crohn's disease characterized by an Harvey-Bradshaw score less or equal than 8 and diagnosed on clinical, endoscopic, histological and/or radiological criteria for more than 3 months,
* Colonoscopy less than a year old without ulcer in the rectum,
* Presence of complex chronic perianal fistula with a maximum of two internal ports and three external ports,
* Patient treated with a combined treatment (drainage on setons + anti-TNFα) and who failed conventional treatment after 6 months and whose intraluminal disease (intestinal damage) is controlled

Exclusion Criteria:

* Refusal of the patient to participate in the study,
* Positive QuantiFERON test,
* Patient with transplanted organ,
* History of cancer in the last five years or lympho-proliferative disease,
* Persistent bacterial or viral infection,
* Patient with a contraindication to MRI,
* Known allergy to Gadolinium,
* Known allergy to Albumine,
* End-stage organ failure,
* Pregnant or breastfeeding women,
* Women of childbearing age without effective contraception throughout the duration of the study,
* Patient under judicial protection, under guardianship or curatorship.
* Patient previously treated with ALOFISEL®

Primary outcomes:
measure: adverse events of grade ≥ 2 at 6 months
timeFrame: 6 months after injection
measure: Efficacy of AdMSC by clinical evaluation at 6 months
timeFrame: 6 months after injection
measure: Efficacy of AdMSC by radiological evaluation at 6 months
timeFrame: 6 months after injection
Secondary outcomes:
measure: Safety at 1 and 3 and 6 months
timeFrame: 1, 3 and 6 months after injection
measure: Efficacy of AdMSC by clinical evaluation 1 and 3 months
timeFrame: 1 and 3 months after injection
measure: Efficacy of AdMSC by biological evaluation
timeFrame: 1, 3 and 6 months after injection
measure: Change from Baseline in quality of life
timeFrame: 1, 3 and 6 months after injection
measure: Change from Baseline in disease activity
timeFrame: 1, 3 and 6 months after injection
measure: Change from Baseline in perianal disease activity
timeFrame: 1, 3 and 6 months after injection
measure: Change from Baseline in lesions
timeFrame: 1, 3 and 6 months after injection
measure: Change from Baseline in anal incontinence
timeFrame: 1, 3 and 6 months after injection
measure: Change from Baseline in patient symptoms
timeFrame: 1, 3 and 6 months after injection
measure: tryptophan metabolists
timeFrame: 3 and 6 months after injection
measure: faecal microbiota
timeFrame: 3 and 6 months after injection
Other outcomes:
Locations:
city: Toulouse
country: France
facility: Toulouse Hospital
Study officials:
affiliation: Toulouse Hospital
name: Etienne BUSCAIL, MD
role: PRINCIPAL_INVESTIGATOR
References: