Evaluation of Local Co-administration of Autologous ADIpose Derived Stromal Vascular Fraction With Microfat for Refractory Perianal CROHN’s Fistulas : ADICROHN II

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], Phenomena and Processes [G] - Digestive System and Oral Physiological Phenomena [G10]

Trial duration

24 Oct 2024 → ongoing

Decision date (initial)

2024-10-24

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

DGOS

External identifiers

EU CT number

2024-517794-24-00

EudraCT number

2019-001948-21

ClinicalTrials.gov

NCT04010526

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy

assess the efficacy of local injection of autologous ADSVF and microfat versus placebo for the treatment of complex refractory perianal Crohn’s fistulas at week 24 (W24)

Secondary objectives 9

1. assess the superiority of the autologous cellular treatment versus placebo on complete (defined by a complete cessation of suppuration) and partial (defined by significant reduction of discharge) response at W4, W12, W24 and W52
2. to assess the superiority of the autologous cellular treatment versus placebo on complete healing (defined as clinical assessment of closure of all the external openings) at W4, W12, W24 and W52
3. to assess the superiority of the autologous cellular treatment versus placebo on reduction in the severity of perianal Crohn’s disease (Perianal Disease Activity Index PDAI), improvement of Quality of Life Short Inflammatory Bowel Disease Questionnaire (SIBDQ) (QoL), Crohn’s Disease Activity Index (CDAI), reduction of anal incontinence severity (Wexner score) (at W4, W12, W24 and W52)
4. safety assessment
5. analyze whether the proposed treatment induces changes in blood immune-inflammatory profile (assessed by quantification of regulatory lymphocyte subsets and soluble inflammatory molecules) at W4 compared to D0
6. analyze whether change in blood immune-inflammatory profile at W4 (assessed by quantification of regulatory lymphocyte subsets and soluble inflammatory molecules) can associate with the individualized clinical response assessed at W12 and W24
7. analyze the potential relationship between biological characteristics of ADSVF (cellular composition, secretory activity and transcriptional profile) and the individualized clinical response at W12 and W24 (in patients who received cellular treatment)
8. analyze whether the initial biological profile evaluated by global transcriptomic approach of intestinal mucosal biopsy performed on day of treatment can associate with the individualized clinical response at W12 and W24 (in patients who received cellular treatment)
9. to identify MRI charasteristics of fistula at baseline that will predict response to treatment at week 24 and 52 and identify MRI charasteristics at week 24 related to response at week 52

Conditions and MedDRA coding

crohn disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Signed informed consent
2. Patients with Crohn’s Disease (CD) diagnosed at least 6 months earlier in accordance with accepted clinical, endoscopic, histological and/or radiologic criteria
3. Presence of one or more refractory perianal fistula(s) assessed by clinical assessment during examination under anaesthesia (preparation treatment) and MRI
4. Non-active or mildly active luminal CD defined as a CDAI ≤ 220
5. Patients of either sex aged 18 years or older
6. Good general state of health according to clinical history and a physical examination
7. For women of a childbearing age, they must have negative serum or urine pregnancy test (sensitive to 25 IU human chorionic gonadotropin [hCG]). Both men and women should use appropriate birth control methods defined by the investigator.
8. Affiliation to a social security scheme

Exclusion criteria 23

1. Presence of dominant luminal active Crohn’s disease requiring immediate therapy
2. CDAI > 220
3. Patient naïve to specific treatment for perianal fistulising Crohn’s disease
4. Presence of an abscess or collections > 2 cm, unless resolved in the preparation procedure
5. Rectal and/or anal stenosis, if this means a limitation for any surgical procedure
6. Patient with ongoing steroid treatment or treated with steroids in the last 4 weeks
7. Malignant tumour or patients with a prior history of any malignant tumour, including any type of fistula carcinoma within 5 years prior to enrolment into this clinical study
8. Congenital or acquired immunodeficiencies
9. Contraindication to local anaesthetics or gadolinium (MRI contrast)
10. Contraindication to MRI scan, (e.g., due to the presence of pacemakers, hip replacements or severe claustrophobia)
11. Pregnant or breastfeeding women
12. Contraindication to the anaesthetic or surgical procedure
13. BMI < 18 kg/m2 to insure adequate abdominal or other subcutaneous adipose tissue accessible by lipoharvest
14. Any active viral infection following: HIV, HTLV I and II, VHB, VHC and Syphillis
15. Bleeding disorders precluding surgical procedure
16. Patients with known hypersensitivity to human albumin
17. Participation in an another clinical trial
18. Adults without legal capacity
19. Patients in Health and Social Establishments
20. Persons in emergency situations
21. Persons deprived of their liberty
22. Non Affiliated to a social security scheme
23. Absence or refusal of the informed consent

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. clinical assessment of closure (despite gentle finger compression) of all the external openings that were drained at baseline
2. MRI confirmation of absence of collections > 2 cm of the treated perianal fistulas at week 24

Secondary endpoints 8

1. assesment of complete cessation of suppuration
2. significant reduction of discharge
3. clinical assessment of closure of all the external openings
4. severity of perianal Crohn’s disease (Perianal Disease Activity Index PDAI), improvement of Quality of Life Short Inflammatory Bowel Disease Questionnaire (SIBDQ) (QoL), Crohn’s Disease Activity Index (CDAI), reduction of anal incontinence severity (Wexner score)
5. assessment of adverse events, severity, and causal relationship to study product
6. assessment of quantification of regulatory lymphocyte subsets and soluble inflammatory molecules
7. cellular composition, secretory activity and transcriptional profile
8. MRI charasteristics of fistula

Investigational products

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

Test 1

Placebo 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

Mélanie SERRERO

Public contact point

Organisation

Centre Hospitalier Regional De Marseille

Contact name

Amandine ROLLAND-BRUN

Locations

1 EU/EEA country · 4 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Corrective measures 1 · Art. 77 CTR

Results and documents

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

Documents 8 files

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

Application history

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