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

NCT04543994 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: 20-1005
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

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.

Conditions

Ulcerative Colitis

Keywords

Ulcerative Colitis; medically refractory ulcerative colitis; UC; refractory ulcerative colitis

Outcome Measures

Primary Outcomes (1)

• Treatment related adverse events

  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.

  Month 3

Secondary Outcomes (5)

• Clinical and endoscopic remission

  Month 3, Month 12

• Clinical and endoscopic response

  Month 3, Month 12

• Partial clinical and endoscopic response

  Month 3, Month 12

• Lack of response

  Month 3, Month 12

• Mayo clinic score

  Month 1 through Month 24

Other Outcomes (4)

• Inflammatory bowel disease questionnaire

  Month 1 through Month 24

• EuroQol 5 Dimensions survey

  Month 1 through Month 24

• IBD-patient reported treatment impact survey

  Month 1 through Month 24

Study Arms (3)

Remestemcel-L (150 million cells)

EXPERIMENTAL

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).

Drug: Remestemcel-L

Remestemcel-L (300 million cells)

EXPERIMENTAL

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).

Drug: Remestemcel-L

Placebo

PLACEBO COMPARATOR

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).

Other: Placebo

Interventions

Placebo OTHER

Normal saline

Placebo

Remestemcel-L DRUG

An ex vivo culture-expanded adult allogeneic bone marrow derived mesenchymal stem cell product for the treatment of medically refractory ulcerative colitis

Remestemcel-L (150 million cells)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and Females 18-75 years of age.
• Ulcerative colitis of at least 6 months duration with medically refractory symptoms
• Exposure to corticosteroids, 5-ASA drugs, thiopurines, methotrexate, anti-TNF therapy, anti-integrin and anti-interleukin in the past are permitted but a washout period of 4 weeks for any monoclonal antibody is necessary.
• If receiving conventional immunomodulators (ie, AZA, 6-MP, or MTX), must have been taking them for ≥12 weeks, and on a stable dose for at least 4 weeks.
• If AZA, 6-MP, or MTX has been recently discontinued, it must have been stopped for at least 4 weeks.
• If receiving oral 5-ASA compounds, the dose must have been stable for at least 4 weeks.
• If receiving oral corticosteroids, the dose must be ≤20 mg/day prednisone or its equivalent and must have been stable for at least 4 weeks.
• If receiving budesonide, the dose must have been stable for at least 2 weeks.
• If oral 5-ASA compounds or oral corticosteroids (including budesonide) have been recently discontinued, they must have been stopped for at least 2 weeks.
• The following medications/therapies must have been discontinued before first administration of study agent:
• TNF-antagonist therapy (eg, infliximab, etanercept, certolizumab, adalimumab, golimumab), vedolizumab, ustekinumab for at least 4 weeks.
• Cyclosporine, tacrolimus, or sirolimus, for at least 4 weeks.
• thioguanine (6-TG) must have been discontinued for at least 4 weeks.
• Rectal corticosteroids (ie, corticosteroids \[including budesonide\] administered to the
• rectum or sigmoid colon via foam or enema or suppository) for at least 2 weeks.

You may not qualify if:

• Inability to give informed consent.
• Clinically significant medical conditions within the six months before administration of MSCs: e.g. myocardial infarction, active angina, congestive heart failure or other conditions that would, in the opinion of the investigators, compromise the safety of the patient.
• HIV
• Hepatitis B or C
• Abnormal AST or ALT at screening defined as AST \>100 or ALT \> 100
• Abnormal basic laboratory values with the following cut-offs:
• Alkaline phosphate \>200
• WBC \>13
• Hemoglobin \<7
• Platelets \<50 or \> 1 million
• Creatinine \>1.5
• History of cancer including melanoma (with the exception of localized skin cancers) within 5 years of study enrollment
• Investigational drug within one year of study enrollment
• Pregnant or breast feeding.
• Fulminant colitis requiring emergency surgery

Sponsors & Collaborators

• The Cleveland Clinic: lead
• Mesoblast, Inc.: collaborator

Study Sites (1)

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Related Publications (2)

• Sandborn WJ, Feagan BG, Rutgeerts P, Hanauer S, Colombel JF, Sands BE, Lukas M, Fedorak RN, Lee S, Bressler B, Fox I, Rosario M, Sankoh S, Xu J, Stephens K, Milch C, Parikh A; GEMINI 2 Study Group. Vedolizumab as induction and maintenance therapy for Crohn's disease. N Engl J Med. 2013 Aug 22;369(8):711-21. doi: 10.1056/NEJMoa1215739.

  PMID: 23964933 BACKGROUND

• Kin C, Kate Bundorf M. As Infliximab Use for Ulcerative Colitis Has Increased, so Has the Rate of Surgical Resection. J Gastrointest Surg. 2017 Jul;21(7):1159-1165. doi: 10.1007/s11605-017-3431-0. Epub 2017 May 8.

  PMID: 28484890 BACKGROUND

MeSH Terms

Conditions

Colitis, Ulcerative

Interventions

remestemcel-l

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Inflammatory Bowel Diseases; Colonic Diseases; Intestinal Diseases

Study Officials

• Amy Lightner

  Cleveland Clinic Foundation, Cleveland OH

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 3, 2020
• First Posted: September 10, 2020
• Study Start: November 10, 2020
• Primary Completion: November 15, 2023
• Study Completion: November 15, 2023
• Last Updated: April 16, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)