Study of Mesenchymal Stem Cells for the Treatment of Medically Refractory Ulcerative Colitis (UC)

Phase 1

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

• Registration Number: NCT04543994
• Lead Sponsor: The Cleveland Clinic

Brief Summary

The purpose of this study is to determine the safety and efficacy of using remestemcel-L, an ex vivo culture-expanded adult allogeneic bone marrow derived mesenchymal stem cell product (MSCs) delivered by targeted endoscopic delivery to treat people for medically refractory ulcerative colitis.

This study will enroll adult patients with medically refractory ulcerative colitis who are planning to switch biologic therapy or undergo colectomy as the next stage in their treatment plan.

Detailed Description

Ulcerative colitis (UC) is an idiopathic chronic inflammatory disease of the colon and rectum, which continues to increase in incidence for unknown reasons, resulting in a significant burden to the healthcare system. UC is characterized by persistent mucosal inflammation of the colon and rectum with a chronic remitting and relapsing behavior which leaves patients on chronic immunosuppression and hospitalizations to treat the disease symptoms, but unable to cure the disease. Despite the ever-growing armamentarium of immunosuppressive medication, up to 30% of patients still require a colectomy for medically refractory disease.

Participants with medically refractory ulcerative 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 ulcerative colitis.

Study Timeline

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

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
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).
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).

Primary Outcome Measures

Name	Time	Method
Treatment related adverse events	Month 3	Number of participants with treatment related adverse events post-injection of 150 or 300 million allogeneic bone marrow derived mesenchymal stem cells for the treatment of medically refractory Ulcerative colitis as assessed by protocol CCF-Stem Cells IBD-005.

Secondary Outcome Measures

Name	Time	Method
Clinical and endoscopic remission	Month 3, Month 12	Number of participants with clinical and endoscopic remission post-injection of 150 or 300 million bone marrow allogeneic derived mesenchymal stem cells for the treatment of medically refractory Ulcerative colitis.; Clinical and endoscopic remission is defined as: Clinical remission: Mayo Clinic score of 2 or lower and no subscore higher than 1, and mucosal healing, defined as an endoscopic subscore of 0 or 1; Endoscopic remission: Mayo Clinic scale endoscopic subscore of 0 or 1
Clinical and endoscopic response	Month 3, Month 12	Number of participants with a clinical and endoscopic response post-injection of 150 or 300 million allogeneic bone marrow derived mesenchymal stem cells for the treatment of medically refractory Ulcerative colitis.; Clinical and endoscopic response is defined as: Clinical response: Reduction in the Mayo Clinic score by 3 points and a decrease of at least 30% from the baseline score with a decrease of at least 2 points on the rectal bleeding subscale to an absolute rectal bleeding score of 1 or 2.; Endoscopic response: Mayo Clinic scale endoscopic subscore decrease by at least one point
Partial clinical and endoscopic response	Month 3, Month 12	Number of participants with a partial clinical and endoscopic response post-injection of 150 or 300 million allogeneic bone marrow derived mesenchymal stem cells for the treatment of medically refractory Ulcerative colitis.; Partial clinical and endoscopic response is defined as: Partial clinical response: Reduction in the Mayo Clinic score that does not meet the following: by 3 points and a decrease of at least 30% from the baseline score with a decrease of at least 2 points on the rectal bleeding subscale to an absolute rectal bleeding score of 1 or 2; Partial endoscopic response: No improvement in Mayo Clinic scale endoscopic subscore that stays the same or decreases
Lack of response	Month 3, Month 12	Number of participants with a lack of response post-injection of 150 or 300 million allogeneic bone marrow derived mesenchymal stem cells for the treatment of medically refractory Ulcerative colitis.; Lack of response is defined as: Clinical response: No improvement in Mayo Clinic score; Endoscopic response: No improvement or worsening in Mayo Clinic scale endoscopic subscore
Mayo clinic score	Month 1 through Month 24	Mayo clinic score will be used to measure quality of life in participants.; \*Score ranges from 0 (least severe) to 12(most severe).

Trial Locations

Locations (1)

Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States