Phase II Multicenter Study on Laparoscopic Administration of Allogeneic Adipose-Derived Mesenchymal Stem Cells for Crohn's Disease-Associated Strictures

Trial ID: 2023-507108-30-00
Protocol: FJD-MEIC-21-01
Sponsor: Instituto De Investigacion Sanitaria Fundacion Jimenez Diaz

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Diseases & Conditions

Crohn's disease

Objectives

The primary objective of this phase II, national, multicenter, uncontrolled, and open trial is to evaluate the **feasibility** and **safety** of laparoscopic administration of allogeneic adipose tissue-derived mesenchymal stem cells (adMSCs) for the treatment of patients with inflammatory bowel strictures associated with **Crohn's disease**. This is clinically relevant as it explores a novel therapeutic approach that could potentially address complications associated with Crohn's disease, offering insights into the management of bowel strictures.

Secondary objectives include:

To assess preliminary treatment efficacy, providing initial data on the potential benefits of the intervention.
To evaluate changes in the quality of life of treated patients using the IBDQ32 questionnaire, which is crucial for understanding the broader impact of the treatment on patient well-being.

Participants

The clinical trial involves participants diagnosed with **Crohn's disease**, specifically those experiencing inflammatory bowel strictures. The study population includes both male and female subjects aged between 18 and 75 years. Participants are required to have been diagnosed with Crohn's disease at least six months prior to the study and must present with a single inflammatory stenotic lesion in the small bowel or ileocolic area. The trial does not include a vulnerable population. Participants must have been treated with at least one biologic drug, such as anti-TNF, anti-integrin, or anti-IL-12/23, with an inadequate response to maintenance doses. Women of childbearing age are required to have a negative pregnancy test at screening and must agree to use effective contraceptive measures during the study. The sponsor has not provided information regarding the total number of participants in the trial.

Plans and Procedures

The clinical trial is designed as a **phase II**, national, multicenter, uncontrolled, and open-label study aimed at evaluating the feasibility and safety of laparoscopic administration of **allogeneic adipose tissue-derived mesenchymal stem cells expanded** for the treatment of patients with inflammatory bowel strictures associated with **Crohn's disease**. The trial is expected to commence recruitment on March 3, 2023, and conclude by November 30, 2025. Participants will be involved in the study for a maximum treatment period of one year, with the primary focus on assessing the proportion and type of complications arising from the treatment, including adverse reactions and complications during anesthesia.

The study will include an initial screening visit to confirm eligibility based on specific inclusion criteria, such as age between 18 and 75 years, a diagnosis of Crohn's disease at least six months prior, and the presence of a single inflammatory stenotic lesion. Women of childbearing age must have a negative pregnancy test and agree to use effective contraceptive measures. Follow-up visits will be scheduled at 6, 12, 18, 24, 36, and 52 weeks to evaluate changes in the length of stenosis, the **CDAI** questionnaire score, and the **IBDQ32** questionnaire score. The end-of-study visit will assess the overall safety and efficacy outcomes, including the number of patients requiring resection surgery due to obstructive episodes.

Participants may be withdrawn from the study if they experience significant adverse events, fail to comply with study procedures, or withdraw consent. The trial does not include a control group, and the investigational product is administered as an injectable solution. The study aims to provide insights into the potential therapeutic benefits of cell therapy in managing complications associated with Crohn's disease, with a focus on safety and feasibility.

Treatment

The clinical trial involves the administration of **allogeneic adipose tissue-derived mesenchymal stem cells expanded** as the experimental treatment. This investigational product is a **suspension for injection** and is classified as a cell therapy medicinal product. The active substance, **allogeneic adipose tissue-derived mesenchymal stem cells expanded**, is derived from lipoaspirate of healthy donors. The maximum daily dose is set at 120 million cells, with the same amount being the maximum total dose for the treatment period. The administration route is via injectable solution, specifically through laparoscopic administration, and the treatment period is limited to one day. The product is not formulated for pediatric use and is not designated as an orphan drug.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The trial is designed to evaluate the feasibility and safety of the experimental treatment in patients with inflammatory bowel strictures associated with Crohn's disease. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the protocol. The trial is conducted under a national, multicenter, uncontrolled, and open-label design, focusing on the specific administration technique and its outcomes.

Efficacy

Efficacy in this clinical trial will be assessed through both primary and secondary endpoints. The primary endpoints focus on the proportion and type of complications arising from treatment, including adverse reactions and complications during anesthesia, as well as those arising from the treatment administration procedure. Secondary endpoints include evaluating changes in the length of the stenosis compared to baseline as measured by enteroresonance, and changes in the Crohn's Disease Activity Index (CDAI) questionnaire score from baseline at multiple timepoints: 6, 12, 18, 24, 36, and 52 weeks. Additionally, changes in the score from baseline on the Inflammatory Bowel Disease Questionnaire (IBDQ32) will be assessed at the same intervals. The study will also describe the number of patients with obstructive episodes who required resection surgery during the study period. These assessments will provide a comprehensive evaluation of the treatment's efficacy in patients with inflammatory bowel strictures associated with **Crohn's disease**.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Patients who agree to participate and agree to give their written consent
Patients over 18 years of age and under 75 years of age
With Crohn's disease diagnosed at least 6 months earlier who meet clinical, endoscopic, histological and/or radiological criteria
Presence of a single inflammatory stenotic lesion in the small bowel or ileocolic area or anastomotic area of the small bowel or ileocolic area, either recent, or in the context of inflammatory recurrence, with a maximum length of 10 cm, demonstrated by enteroresonance, resulting in episodes of intestinal occlusion/subocclusion. Other inflammatory lesions are acceptable, but only one lesions are acceptable, but only one should be identified as the obvious cause of the occlusion/subocclusion. occlusion/subocclusion
Patients treated with at least one biologic drug and with inadequate response to maintenance doses and prior to intensification (either dose, interval or change/addition of another drug): a. anti-TNF (for at least 14 weeks, which includes induction and/or maintenance doses): Infliximab, Adalimumab, Certolizumab. b. Anti-integrin(at least for 14 weeks, which includes induction and/or maintenance doses): Vedolizumab c. Anti-IL-12/23(at least for 16 weeks, which includes induction and/or maintenance doses): Ustekinumab
Women of childbearing age must have a negative pregnancy test at screening and agree to use effective contraceptive measures for the duration of their participation in the study

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Exclusion Criteria

Intra-abdominal abscesses larger than 3 cm not drained (surgically, by interventional radiology) or not treated with antibiotics. Patients may be included once the abscess has been drained (no need to wait) or if they have received antibiotic treatment, once improvement has been confirmed with imaging tests.
Severe intestinal obstruction requiring urgent surgery.
Active Crohn's disease flare-up requiring medical treatment, defined as abdominal pain, fever, bloody diarrhea and CRP greater than 10. The patient may be included once the condition has resolved, when the patient is on maintenance medication.
History of previous invasive neoplasia in the last 5 years. Patients with completely resected basal cell carcinoma of the skin can be included.
History in the last 6 months of severe, progressive or uncontrolled hepatic, hematologic, gastrointestinal, renal, endocrine, pulmonary, cardiac, neurologic or psychiatric disease.
Patients with primary sclerosing cholangitis.
Patients with known congenital or acquired immune deficiency, including HIV.
Known allergy or hypersensitivity to penicillin or aminoglycosides; DMEN (dulbecco modified eagle's medium), bovine serum, local anesthetic or gadolinium.
Contraindication to perform MRI (pacemaker, hip prosthesis or severe claustrophobia) or receive contrast with gadolinium.
Patients unwilling or unable to comply with the study procedures.
Patients who are receiving, or have received, any investigational drug in the 3 months prior to the screening period.
Major surgery or severe trauma in the previous 6 months
Pregnant or breastfeeding women.
Patients with contraindications for general anesthesia, locoregional anesthesia (depending on the type of anesthesia required) or laparoscopic surgery.