Tolerance of local administration of cryopreserved autologous stromal vascular fraction combined with micrograft for the treatment of refractory ano-perineal fistulas in Crohn's disease

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Regional De Marseille

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

29 Dec 2025 → ongoing

Decision date (initial)

2025-06-02

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

DGOS - PHCRI

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Bioequivalence, Safety

To evaluate the overall safety profile of cryopreserved autologous VSF injection combined with autologous microfat in the treatment of refractory anoperineal fistulas associated with Crohn's disease.

Secondary objectives 9

1. Evaluate remission induced by cryopreserved FVS injection, per patient and per fistula. A subgroup will focus on recto-vaginal fistulas.
2. Evaluate remission induced by injection of a second dose of FVS in previously treated patients, per patient and per fistula. A subgroup will focus on recto-vaginal fistulas.
3. Evaluate the tolerability of a second dose of FVS in previously treated patients.
4. Evaluate the complete clinical response, per patient and per fistula. A subgroup will focus on recto-vaginal fistulas.
5. Evaluate partial clinical response, by patient and by fistula. A subgroup will focus on recto-vaginal fistulas.
6. Compare patients' quality of life before and after treatment.
7. Compare the severity of perineal damage in patients before and after treatment.
8. Compare patients' disease activity before and after treatment.
9. Evaluate external orifice closure, by patient and by fistula A subgroup will focus on recto-vaginal fistulas

Conditions and MedDRA coding

Crohn's disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Signature of a consent form.
2. Patients with Crohn's disease diagnosed at least 6 months previously, according to clinical, endoscopic, histological and/or radiological criteria.
3. Patients previously included/treated in the ADICROHN 2 study.
4. Luminal non-active or weakly active Crohn's disease, defined by a CDAI score ≤ 220.
5. Patients with ADICROHN-2 protocol response failure, defined by persistence of anoperineal fistula(s) at the end of the ADICROHN-2 study and their persistence at the time of inclusion.
6. Successful patients (combined remission) at the end of the ADICROHN-2 study but with recurrence of the anoperineal fistula(s) at the time of inclusion.
7. Sufficient quantity of cryopreserved cells to enable innovative treatment, at a rate of at least 30 million frozen cells per fistula pathway based on the number of fistulas to be treated.
8. Patients over 18 years of age.
9. Good general health according to history and clinical examination.
10. Women of childbearing age must have a negative pregnancy test (serum or urine) (detection threshold: 25 mIU hCG/ml). Patients of both sexes should use reliable contraception.
11. Affiliation to a social security system.

Exclusion criteria 16

1. Active, mainly luminal Crohn's disease requiring immediate treatment.
2. Patient with intolerance to advanced therapy drug in ADICROHN-2 study.
3. Presence of abscess or collections > 2 cm at time of inclusion, unless resolved during fistula preparation.
4. Rectal and/or anal stenosis and/or active rectitis resulting in limited surgical access.
5. Patients on corticosteroids or having received them in the four weeks preceding injection of the experimental product.
6. Malignant tumors or history of malignant tumors less than 5 years old.
7. Congenital or acquired immunodeficiency.
8. Contraindications to local anesthetics and gadolinium (MRI contrast agent).
9. Contraindications to MRI: metallic foreign bodies (ferromagnetic material) and metallic implants (pacemakers, heart valves, vascular clips, surgical clips or staples, cochlear implants, any implanted electronic medical equipment or devices (e.g. insulin pumps), orthopedic medical prostheses.
10. Treatment with darvadstrocel < 6 months prior to inclusion.
11. Contraindications to general anesthesia.
12. BMI < 18 kg/m2 to ensure sufficient abdominal or other subcutaneous adipose tissue accessible by manual liposuction.
13. Coagulation disorders contraindicating surgery.
14. Known hypersensitivity to human albumin.
15. Participation in another clinical trial (other than an observational study).
16. Persons protected by articles L1121-5, L1121-6 and L1121-8 of the French Public Health Code (pregnant or breast-feeding women, persons deprived of their liberty by court order, socially vulnerable persons, adults incapable or unable to give consent).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. Absence of local infectious complications, defined by the absence of local inflammatory signs: pain, and/or erythematous placard, and/or swelling or induration at 6 months, cumulating all assessments at each visit (1 week and at 1, 3 and 6 months).
2. The absence of general infectious complications, defined by the absence of general infectious signs: fever, chills, mottling, hypotension at 6 months, cumulating all assessments at each visit (1 week and at 1, 3 and 6 months).
3. No increase in anal incontinence compared with the pre-therapeutic evaluation, as assessed by the Wexner index at 6 months, cumulating all assessments at each visit (1 week and at 1, 3 and 6 months).
4. The absence of any other adverse events considered potentially related to the experimental treatment at 6 months, cumulating all assessments at each visit (1 week and at 1, 3 and 6 months).

Secondary endpoints 9

1. Remission induced by cryopreserved FVS injection is assessed at 6 months and defined by closure of the external os and absence of collection > 2cm on MRI (= combined remission).
2. Remission induced by injection of a second dose of FVS is assessed at 6 months and defined by closure of the external os and absence of collection > 2cm on MRI (= combined remission)..
3. Tolerability of a second dose of FVS is defined by evaluation of the overall tolerance profile (see primary endpoint). It is assessed at 6 months as for the primary endpoint.
4. Complete clinical response is assessed at 1 week, 1, 3 and 6 months, and defined by the cessation of suppurations.
5. Partial clinical response is assessed at 1 week, 1, 3 and 6 months and defined by significant reduction in suppuration (reduction ≥ 2 points on the 5-point suppuration scale).
6. Quality of life is assessed at 1, 3 and 6 months using the Short Inflammatory Bowel Disease Questionnaire (SIBDQ).
7. Severity of perineal damage is assessed at 1 week and at 1, 3 and 6 months using the Perineal Disease Activity Index (PDAI).
8. Patients' disease activity is assessed at 1, 3 and 6 months by the Crohn's Disease Activity Index (CDAI), and at 6 months by fecal calprotectin.
9. Closure of the external ostium is assessed at 1 week and at 1, 3 and 6 months, and defined by healing of the ostium or absence of suppuration despite slight digital compression.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Regional De Marseille

Sponsor organisation

Centre Hospitalier Regional De Marseille

Address

265 Chemin Des Bourrely

City

Marseille

Postcode

13015

Country

France

Scientific contact point

Organisation

Centre Hospitalier Regional De Marseille

Contact name

Lucas GUILLO

Public contact point

Organisation

Centre Hospitalier Regional De Marseille

Contact name

Lucas GUILLO

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 7 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications