Treatment of refractory Crohn's disease lesions by local injection of mesenchymal stem cells

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre hospitalier universitaire de Liege

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

1 Mar 2018 → 21 Apr 2026

Decision date (initial)

2024-10-09

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-514033-37-00

EudraCT number

2017-002653-11

ClinicalTrials.gov

NCT03901235

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To assess the safety and efficacy of local injection of mesenchymal stem cells on healing of refractory intestinal and perianal lesions in Crohn’s disease

Secondary objectives 1

1. To assess the evolution of clinical indices of activity, quality of life, patient reported outcomes, tissue damage index and obstructive score of local injection of mesenchymal stem cells on refractory intestinal and perianal lesions in Crohn's disease

Conditions and MedDRA coding

Crohn's Disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Patients ≥ 18 years of age
2. Patients signing the informed consent
3. Diagnosis of Crohn's Disease for more than 6 months
4. Presence of at least one CD lesion refractory to conventional therapies (azathioprine, 6- mercaptopurine or methotrexate) and to biologic treatments (anti-TNF therapies, vedolizumab, or ustekinumab).
5. Refractory lesion defined by (1) a stricture with a length of 2 to 5cm of the colon or the ileum accessible by ileocolonoscopy (i.e. a lesion identified during a colonoscopy with a lumen narrowing non passable by the colonoscope), (2) unhealed deep ulcer of the colon or the ileum accessible to ileocolonoscopy, or (3) actively draining perianal fistula(s)
6. 15 patients with stricture(s), 5 patients with unhealed deep ulcer(s), and 50 patients with an actively draining perianal fistula(s) will be included.

Exclusion criteria 11

1. Indication for immediate luminal surgery
2. Intestinal obstruction
3. Intra-abdominal fistulas or abscess
4. Intestinal/colonic stricture or deep unhealed ulcer not accessible to ileocolonoscopy
5. Undrained peri-anal abscess
6. Pregnant women or planning pregnancy within one year
7. Positive stool culture/toxin for clostridium difficile pathogen or other pathogens
8. Renal failure (anuria, serious fluid overload, GFR < 30 ml/min, dialysis) or hepatic failure (fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evinced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin >3 mg/dL)
9. Documented human immunodeficiency virus infection; active hepatitis B, C, or tuberculosis
10. Opportunistic infection within 6 months before screening or a serious infection in the previous 3 months
11. Malignancy within the past 5 years; or a history of lymphoproliferative disease

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. The first co-primary endpoint will be the complete or partial healing of the refractory lesion at 12 weeks.
2. The second co-primary endpoint is safety, assessed by monitoring for adverse and serious adverse events and changes in vital signs at the day of treatment and at all follow-up visits.

Secondary endpoints 8

1. Complete or partial healing of the refractory lesion at 48 weeks
2. Evolution of the Patient Reported Outcomes (PRO), between week 0, 12 and 48, including pain, general well-being and number of stools per day
3. Evolution of Crohn's Disease Activity Index (CDAI) between weeks 0, 12 and 48
4. Evolution of the Short health scale SHS (quality of life) between week 0, 12 and 48
5. Evolution of the Lemann Index between week 0, 12 and 48
6. Evolution of the GETAID obstructive score for Crohn's Disease strictures between weeks 0, 12 and 48
7. Disappearance or improvement of intestinal or colonic ulcers/stricture at MRI at 12 and 48 weeks
8. Incidence of specific safety outcomes all over the study period and more specifically at week 0, 4, 12, 24, and 48: (1) the occurrence of an obstruction requiring hospitalisation and fasting for at least 24 hours, (2) the occurrence of an intestinal perforation, (3) the development of an intra-abdominal fistula and/or abscess, (4) perianal abscess, (5) new perianal fistulous track.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre hospitalier universitaire de Liege

Sponsor organisation

Centre hospitalier universitaire de Liege

Address

Avenue De L'hopital 1

City

Liege

Postcode

4000

Country

Belgium

Scientific contact point

Organisation

Centre hospitalier universitaire de Liege

Contact name

Prof. Edouard Louis

Public contact point

Organisation

Centre hospitalier universitaire de Liege

Contact name

Prof. Edouard Louis

Locations

1 EU/EEA country · 1 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

Temporary halts 1 · Art. 38 CTR

Results and documents

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

Documents 12 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