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

NCT04548583 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: 20-845
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

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.

Conditions

Crohn Colitis

Outcome Measures

Primary Outcomes (1)

• Treatment related adverse events

  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.

  Month 3

Secondary Outcomes (9)

• Complete clinical healing

  Month 3, Month 12

• Clinical response

  Month 3, Month 12

• Partial clinical response

  Month 3, Month 12

• Lack of response

  Month 3, Month 12

• Crohn's disease activity index

  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

Remestemcel-L DRUG

adult allogeneic bone marrow derived mesenchymal stem cell product for the treatment of medically refractory Crohn's colitis

remestemcel-L (150 million cells)

Placebo OTHER

Normal saline

Placebo

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.
• Crohn's colitis of at least 6 months duration with medically refractory symptoms who has failed one anti-TNF therapy, with a next step of subtotal colectomy or escalation in medical management.
• 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.
• Rectal 5-ASA compounds (ie, 5-ASAs administered to the rectum or sigmoid colon viafoam 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 \> 3x upper limit of normal?
• 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.
• If patient is of reproductive capacity, unwilling to use adequate birth control measures while they are in the study
• Fulminant colitis requiring emergency surgery
• Concurrent active clostridium difficile infection of the colon
• Concurrent CMV infection of the colon
• Evidence of colonic perforation
• Massive hemorrhage from the colon requiring emergent surgery
• Ulcerative colitis or indeterminate colitis

Sponsors & Collaborators

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

Study Sites (1)

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

MeSH Terms

Conditions

Crohn Disease

Interventions

remestemcel-l

Condition Hierarchy (Ancestors)

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

Study Officials

• Amy Lightner, MD

  The Cleveland Clinic

  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 14, 2020
• Study Start: November 4, 2020
• Primary Completion: November 15, 2023
• Study Completion: November 15, 2023
• Last Updated: April 16, 2026

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)