Dose Escalation of Allogeneic Adipose Derived Stroma/Stem Cells for the Treatment of Crohn's Fistula (ALLOFIST)

Dose Escalation of Allogeneic Adipose Derived Stroma/Stem Cells for the Treatment of Crohn's Fistula:a Phase I/II Clinical Study

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.

Study Overview

• Status: Recruiting
• Conditions: Crohn Disease
• Intervention / Treatment: Drug: AdMSC (CellReady®)

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.

• Study Type: Interventional
• Enrollment (Estimated): 9
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Etienne BUSCAIL, MD; Phone Number: +33 05 61 32 23 73; Email: buscail.e@chu-toulouse.fr
• Study Contact Backup: Name: Louis BSUCAIL, MD; Phone Number: +33 05 61 32 33 98; Email: buscail.l@chu-toulouse.fr

Study Locations

• France
  • Toulouse, France
    • Recruiting
    • Toulouse Hospital
    • Contact: Etienne BUSCAIL, MD; Phone Number: +33 05 61 32 23 73; Email: buscail.e@chu-toulouse.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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®

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AdMSC (CellReady®); 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	Drug: AdMSC (CellReady®); At day 0, patients will have AdMSC injections. Patients will be followed-up for 6 months; Other Names: AdMSC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
adverse events of grade ≥ 2 at 6 months	Number of adverse events of grade ≥ 2 related to the experimental treatment (CellReady®) or related to surgical/medical procedures,	6 months after injection
Efficacy of AdMSC by clinical evaluation at 6 months	This evaluation will be measured by the presence or absence of flow through the internal or external orifice see in anoscopy and through the external orifice	6 months after injection
Efficacy of AdMSC by radiological evaluation at 6 months	This evaluation will be measured by disappearance of fistula tract or fistula tract present but inactive.	6 months after injection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety at 1 and 3 and 6 months	adverse effects will be assessed	1, 3 and 6 months after injection
Efficacy of AdMSC by clinical evaluation 1 and 3 months	This evaluation will be measured by the presence or absence of flow through the internal or external orifice see in anoscopy and through the external orifice	1 and 3 months after injection
Efficacy of AdMSC by biological evaluation	complete blood count , platelets, C-reactive protein (CRP) , liver enzyme profile, Prothrombin level (TP), activated clotting time (ACT), albumin, ferritinemia will be measured in blood samples	1, 3 and 6 months after injection
Change from Baseline in quality of life	Evaluation of quality of life by CAF QoL	1, 3 and 6 months after injection
Change from Baseline in disease activity	Evaluation of quality of life by Harvey-Bradshaw Index	1, 3 and 6 months after injection
Change from Baseline in perianal disease activity	Evaluation by perianal disease activity index (PDAI) . This index evaluate the presence of a fistula, the presence of pain and its impact on activity, the characteristics of the APL, the impact on the sexual activity	1, 3 and 6 months after injection
Change from Baseline in lesions	Evaluation by Cardiff classifcation . The creation of subclasses of anoperineal lesions allowing the comparison of superimposable groups in therapeutic trials. This classification allows a standardized and precise description of lesions.	1, 3 and 6 months after injection
Change from Baseline in anal incontinence	Evaluation by Wexner anal incontinence score: score to quickly and simply assess the severity of anal incontinence.	1, 3 and 6 months after injection
Change from Baseline in patient symptoms	Evaluation by Allan score: score used to assess patient symptoms and assess the impact of treatment on perineal lesions.	1, 3 and 6 months after injection
tryptophan metabolists	tryptophan metabolists are measured by high pressure liquid chromatography coupled with tandem mass spectrometry	3 and 6 months after injection
faecal microbiota	faecal microbiota is analysed by Illumina Mi-Seq	3 and 6 months after injection

Collaborators and Investigators

• Sponsor: University Hospital, Toulouse
• Investigators: Principal Investigator: Etienne BUSCAIL, MD, Toulouse Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 12, 2025
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: October 8, 2024
• First Submitted That Met QC Criteria: October 9, 2024
• First Posted (Actual): October 10, 2024

Study Record Updates

• Last Update Posted (Actual): December 24, 2025
• Last Update Submitted That Met QC Criteria: December 23, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Crohn's disease; immunomodulation; perianal fistula; regenerative medicine; allogeneic adipose-derived stem cell
• Additional Relevant MeSH Terms: Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Crohn Disease
• Other Study ID Numbers: RC31/13/7030

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No