Study of Mesenchymal Stem Cells for the Treatment of Medically Refractory Crohn's Colitis

Phase 1

• Conditions: Crohn Colitis
• Interventions: Drug: Remestemcel-L; Other: Placebo

• Registration Number: NCT04548583
• Lead Sponsor: The Cleveland Clinic

Brief Summary

Crohn's disease has several phenotypes (inflammatory, stricturing, fistulizing) and location (small bowel, ileocecal, colon, and perianal). Approximately one third of patients have inflammation limited to the colon. Up to two thirds will become medically refractory and require a total abdominal colectomy for symptom control. The purpose of this study is to determine the safety and efficacy of using allogeneic bone marrow derived mesenchymal stem cells (MSCs) delivered by targeted endoscopic delivery to treat people for medically refractory Crohn's colitis.

Detailed Description

Participants with medically refractory Crohn's colitis will be treated by targeted endoscopic delivery of remestemcel-L, an ex vivo culture expanded allogeneic bone marrow derived mesenchymal stem cell product at a dose of 150 or 300 million. This will be injected into the submucosal layer of the colon and rectal wall.

Patients will receive a second dose of remestemcel-L at a dose of 150 or 300 million MSCs (same dose as initial). If at 3 months post injection of remestemcel-L there is clinical remission, escalation of medical management and/or surgery will be delayed and patients observed. If there is worsening or no improvement in treated patients, then patients will proceed with escalation of medical management or colectomy as per standard of care. Control patients without improvement will cross over to receive remestemcel-L at 3 months and may be retreated at 6 months. All patients will be followed for two years post initial treatment.

There will be a total of 4 cohorts of 3 patients (2 treatment:1 control) receiving the 150 million MSC dose of study drug and a total of 4 cohorts of 3 patients (2 treatment:1 control) receiving 300 million MSCs dose of study drug. This study plans to enroll a total of 24 participants.

The primary endpoint of this study is to determine the safety and feasibility of endoscopic injection of remestemcel-L, an ex vivo culture expanded allogeneic bone marrow derived mesenchymal stem cell product for treatment of medically refractory Crohn's colitis.

Study Timeline

• Study First Submitted: 2020-09-03
• Study First Submitted QC: 2020-09-11
• Study First Posted: 2020-09-14
• Study Start: 2020-11-04
• Status Verified: 2022-04
• Last Update Submitted: 2022-04-04
• Last Update Posted: 2022-04-05
• Primary Completion: 2023-10
• Study Completion: 2023-10

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
remestemcel-L (150 million cells)	Remestemcel-L	Targeted endoscopic delivery of remestemcel-L, at a dose of 150 million cells into the submucosal layer of the colon wall at baseline If at 3 months post injection of remestemcel-L there is clinical, endoscopic or radiographic improvement, patients will receive a second dose of remestemcel-L at a dose of 150 million MSCs (same dose at initial)
remestemcel-L (300 million cells)	Remestemcel-L	Targeted endoscopic delivery of remestemcel-L, at a dose of 300 million cells into the submucosal layer of the colon wall at baseline. If at 3 months post injection of remestemcel-L there is clinical, endoscopic or radiographic improvement, patients will receive a second dose of remestemcel-L at a dose of 300 million MSCs (same dose at initial).
Placebo	Placebo	Direct injection of normal saline into the submucosal layer of the colon wall. If not completely healed after 3 months, participants will then cross over to the treatment group to receive a direct injection of remestemcel-L, at a dose of 150 or 300 million cells into the submucosal layer of the colon wall. If at 6 months post injection of remestemcel-L there is clinical, endoscopic or radiographic improvement, patients will receive a second dose of remestemcel-L at a dose of 150 or 300 million MSCs (same dose at initial).

Primary Outcome Measures

Name	Time	Method
Treatment related adverse events	Month 3	The primary endpoint of this study is to determine the safety and feasibility of endoscopic injection of remestemcel-L, an ex vivo expanded allogeneic bone marrow-derived mesenchymal stem cell product, for treatment of medically refractory Crohn's colitis.

Secondary Outcome Measures

Name	Time	Method
Complete clinical healing	Month 3, Month 12	Number of participants with complete clinical healing post-injection of 150 or 300 million bone marrow allogeneic derived mesenchymal stem cells for the treatment of medically refractory Crohn's colitis.; Complete healing is defined as: Clinical and endoscopic remission; Clinical Healing: Normalization of CRP to \<2.87 mg per liter, CDAI drops to \<150; Radiographic Healing: MR enterography with improvement of inflammation; Endoscopic healing: Absence of mucosal ulceration and SES-CD score of 0-5
Clinical response	Month 3, Month 12	Number of participants with clinical response post-injection of 150 or 300 million allogeneic bone marrow derived mesenchymal stem cell product for the treatment of medically refractory Crohn's colitis.; Clinical response is defined as: Clinical Healing: Normalization of CRP to \<2.87 mg per liter, CDAI drops to \<150; Radiographic Healing: MR enterography with improvement of inflammation; Endoscopic healing: Absence of mucosal ulceration and SES-CD score of 0-5
Partial clinical response	Month 3, Month 12	Number of participants with partial clinical response post-injection of 150 or 300 million allogeneic bone marrow derived mesenchymal stem cell product for the treatment of medically refractory Crohn's colitis.; Partial clinical response is defined as: Clinical Healing: \>25% reduction of CRP, decrease in CDAI by \<100 points; Radiographic Healing: MR enterography with improvement in inflammation; Endoscopic healing: Decreased SES-CD by \>25% but \< 50% or to score of 10-15
Lack of response	Month 3, Month 12	Number of participants with lack of response post-injection of 150 or 300 million allogeneic bone marrow derived mesenchymal stem cell product for the treatment of medically refractory Crohn's colitis.; Lack of response is defined as: Clinical Healing: No improvement; Radiographic Healing: MR enterography without resolution of inflammation; Endoscopic healing: No improvement in SES-CD
Crohn's disease activity index	Month 1 through Month 24	Crohn's disease activity index will be used to measure quality of life in participants.; \*Remission of Crohn's disease is defined as CDAI below 150. Severe disease is defined as a value of greater than 450.
Inflammatory bowel disease questionnaire	Month 1 through Month 24	Inflammatory bowel disease questionnaire will be used to measure quality of life in participants.; \*Score ranges from 32 (best health) to 224 (worst health)
EuroQol 5 Dimensions survey	Month 1 through Month 24	EuroQol 5 Dimensions survey will be used to measure quality of life in participants.; \*Score ranges from 5 (full health) to 25 (worst health).
Inflammatory bowel disease patient reported treatment impact survey	Month 1 through Month 24	IBD-patient reported treatment impact survey will be used to measure quality of life in participants.; \*Score ranges from 3 (most satisfied) to 15 (least satisfied)
Short Form 36 health survey	Month 1 through Month 24	Short Form 36 health survey will be used to measure quality of life in participants.; \*Score ranges from 0 (least favorable health state) to 3600 (most favorable health state)

Trial Locations

Locations (1)

Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States