Crohn ColitisPhase 1/2NCT04548583
Study of Mesenchymal Stem Cells for the Treatment of Medically Refractory Crohn's Colitis
A Phase 1/2 study testing Remestemcel-L in people with Crohn Colitis, run by The Cleveland Clinic at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Crohn Colitis
- What is being tested?
- Remestemcel-L
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Nov 2020to 15 Nov 2023
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
- 6-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.
- Parenteral corticosteroids for at least 2 weeks.
- Total parenteral nutrition (TPN) for at least 2 weeks.
- Antibiotics for the treatment of UC (eg, ciprofloxacin, metronidazole, or rifaximin) for atleast 2 weeks.
- No colonic dysplasia and malignancy as ruled out by colonoscopy within 30 days of MSC delivery
- Ability to comply with protocol
- Competent and able to provide written informed consent
- Must have lost response to at least one monoclonal antibody (anti-TNF, anti-interleukin, or anti- integrin therapy), or tofacitinib, or have a contra-indication to biologic therapy
Who cannot join
- 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.
- Specific exclusions;
- HIV
- Hepatitis B or C
- Abnormal AST or ALT at screening defined as > 3x upper limit of normal?
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- 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
- Neoplasia of the colon on preoperative biopsy
- Presence of an ostomy
- Three or more prior small bowel resections
- Colonic stricture that unable to pass an adult colonoscope
- Active or latent tuberculosis
- Unable to wean off corticosteroids
- Patients with primary sclerosing cholangitis
- Patients with a known allergy to DMSO, porcine and/or bovine proteins. Control patients will have additional criteria that need to be met prior to the patients' crossing over to receive treatment.
- Inclusion Criteria for control patients prior to entering the treatment phase:
- Received placebo at the point of first injection
- Completed all study visits to date
- Clinical status has remained the same or improved, not worsened
- Exclusion Criteria for control patients who will be entering the treatment phase:
- Required repeat hospitalization for a colitis flare
- Given oral and intravenous steroids for a colitis flare
- Had worsening abdominal pain frequency of bowel movements, blood in stool
- Desires exclusion from the study to pursue escalation in medical management or surgery
- Has a colonic perforation that requires surgery
- Has colonic bleeding that requires surgery
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase IB/IIA Study of Remestemcel-L, an Ex-vivo Culture-expanded Adult Allogeneic Bone Marrow Derived Mesenchymal Stem Cell Product for the Treatment of Medically Refractory Crohn's Colitis
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.
Read the 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.
- Conditions
- Crohn Colitis
- Being tested
- Remestemcel-L, Placebo
- Medical subject headings
- Crohn Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Remestemcel-LDrug
adult allogeneic bone marrow derived mesenchymal stem cell product for the treatment of medically refractory Crohn's colitis
Remestemcel-LDrug
adult allogeneic bone marrow derived mesenchymal stem cell product for the treatment of medically refractory Crohn's colitis
PlaceboOther
Normal saline
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: 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). Receives: 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). Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Month 3
Secondary outcomes (9)
Complete clinical healing
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
Measured: Month 3, Month 12
Clinical response
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
Measured: Month 3, Month 12
Partial clinical response
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
Measured: Month 3, Month 12
Lack of response
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
Measured: Month 3, Month 12
Crohn's disease activity index
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.
Measured: Month 1 through Month 24
Inflammatory bowel disease questionnaire
Inflammatory bowel disease questionnaire will be used to measure quality of life in participants.
*Score ranges from 32 (best health) to 224 (worst health)
Measured: Month 1 through Month 24
EuroQol 5 Dimensions survey
EuroQol 5 Dimensions survey will be used to measure quality of life in participants.
*Score ranges from 5 (full health) to 25 (worst health).
Measured: Month 1 through Month 24
Inflammatory bowel disease patient reported treatment impact survey
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)
Measured: Month 1 through Month 24
Short Form 36 health survey
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)
Measured: Month 1 through Month 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2020
- Study start4 Nov 2020
- Primary completion15 Nov 2023
- Study completion15 Nov 2023
Why it stopped: PI left Cleveland Clinic
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Crohn ColitisStudies of the same condition, open and under way.
- More trials run by The Cleveland ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Cleveland Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- Mesoblast, Inc.
- Responsible party
- Principal investigator, Anthony Lembo, The Cleveland Clinic
- Investigators
- Amy Lightner, MD, Principal investigator, The Cleveland Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04548583
- Sponsor's protocol ID
- 20-845
- Status last verified
- Nov 2022
- First submitted
- 3 Sep 2020
- Last updated
- 16 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IB/IIA Study of Remestemcel-L, an Ex-vivo Culture-expanded Adult Allogeneic Bone Marrow Derived Mesenchymal Stem Cell Product for the Treatment of Medically Refractory Crohn's Colitis
- ClinicalTrials.gov ID
- NCT04548583
- Acronym / sponsor ID
- 20-845
- Conditions
- Crohn Colitis
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: PI left Cleveland Clinic
- Enrolment
- 7 participants (actual)
- Lead sponsor
- The Cleveland ClinicUniversity, hospital or other
- Collaborators
- Mesoblast, Inc.
- Study start
- 4 Nov 2020 (actual)
- Primary completion
- 15 Nov 2023 (actual)
- Study completion
- 15 Nov 2023 (actual)
- First posted
- 14 Sep 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| remestemcel-L (150 million cells) | Experimental | Drug: Remestemcel-LTargeted 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) | Experimental | Drug: Remestemcel-LTargeted 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 comparator | Other: PlaceboDirect 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). |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- 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.
- The following medications/therapies must have been discontinued before first administration of study agent:
- No colonic dysplasia and malignancy as ruled out by colonoscopy within 30 days of MSC delivery
Key exclusion criteria (35 listed)
- 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.
- Specific exclusions;
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Remestemcel-Ladult allogeneic bone marrow derived mesenchymal stem cell product for the treatment of medically refractory Crohn's colitis | Drug | remestemcel-L (150 million cells) |
| Remestemcel-Ladult allogeneic bone marrow derived mesenchymal stem cell product for the treatment of medically refractory Crohn's colitis | Drug | remestemcel-L (300 million cells) |
| PlaceboNormal saline | Other | Placebo |
Primary outcome
Treatment related adverse events
Time frame: 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.
9 secondary outcomes
Complete clinical healing
Time frame: Month 3, Month 12
Clinical response
Time frame: Month 3, Month 12
Partial clinical response
Time frame: Month 3, Month 12
Lack of response
Time frame: Month 3, Month 12
Crohn's disease activity index
Time frame: Month 1 through Month 24
Inflammatory bowel disease questionnaire
Time frame: Month 1 through Month 24
EuroQol 5 Dimensions survey
Time frame: Month 1 through Month 24
Inflammatory bowel disease patient reported treatment impact survey
Time frame: Month 1 through Month 24
Short Form 36 health survey
Time frame: Month 1 through Month 24
Results and safety
The study was stopped early (reason given: PI left Cleveland Clinic). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Apr 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Amy Lightner, MD principal investigator
The Cleveland Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Remestemcel-L in people with Crohn Colitis, run by The Cleveland Clinic at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 35 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 16 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: PI left Cleveland Clinic). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Treatment related adverse events (time frame: Month 3). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Apr 2026.