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

Overview

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.

Interventions

• Drug AdMSC (CellReady®)
  At day 0, patients will have AdMSC injections. Patients will be followed-up for 6 months

Primary outcome measures

• adverse events of grade ≥ 2 at 6 months [Time frame: 6 months after injection]
• Efficacy of AdMSC by clinical evaluation at 6 months [Time frame: 6 months after injection]
• Efficacy of AdMSC by radiological evaluation at 6 months [Time frame: 6 months after injection]

Secondary outcome measures (11)

• Safety at 1 and 3 and 6 months [Time frame: 1, 3 and 6 months after injection]
• Efficacy of AdMSC by clinical evaluation 1 and 3 months [Time frame: 1 and 3 months after injection]
• Efficacy of AdMSC by biological evaluation [Time frame: 1, 3 and 6 months after injection]
• Change from Baseline in quality of life [Time frame: 1, 3 and 6 months after injection]
• Change from Baseline in disease activity [Time frame: 1, 3 and 6 months after injection]
• Change from Baseline in perianal disease activity [Time frame: 1, 3 and 6 months after injection]
• Change from Baseline in lesions [Time frame: 1, 3 and 6 months after injection]
• Change from Baseline in anal incontinence [Time frame: 1, 3 and 6 months after injection]
• Change from Baseline in patient symptoms [Time frame: 1, 3 and 6 months after injection]
• tryptophan metabolists [Time frame: 3 and 6 months after injection]
• faecal microbiota [Time frame: 3 and 6 months after injection]

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®

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

France · 1 center

• Toulouse Hospital — Toulouse

Publications

• Buscail E, Gilletta de Saint Joseph C, Lebrin M, Frument I, Gross F, Bournet B, Buscail L, Culetto A, Mokrane F, Delchier MC, Quelven I, Daguzan C, Pugnet G, Duffas JP, Ghouti L, Philis A, Carrere N, Lepage B, Le Cosquer G. Rationale and design of the AlloFIST trial: a phase I/IIa study to evaluate dose escalation of allogeneic adipose-derived stroma/stem cells for the treatment of Crohn's fistula PMID 41469061

Identifiers

NCT: NCT06636032 · RC31/13/7030

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗