Mesenchymal Stem Cells for the Treatment of Perianal Fistulizing Crohn's Disease

NCT ID: NCT04519671

Last Updated: 2022-04-05

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-11-19
• Study Completion Date: 2022-11-30

Brief Summary

The purpose of this study is to determine the safety and efficacy of using adult allogeneic bone marrow derived mesenchymal stem cells (MSCs), to treat people for medically refractory perianal fistulizing Crohn's disease.

Detailed Description

Crohn's disease (CD), a chronic transmural inflammatory disease of the gastrointestinal tract, continues to increase in incidence for unknown reasons. According to population based studies, at least 26% of patients with CD will develop perianal fistulas in the first two decades following diagnosis, particularly those with colonic and rectal involvement. These patients experience significant morbidity due to pain, persistent drainage, recurrent perianal sepsis, and ongoing need to access medical care resulting in increased costs and impaired quality of life.

Unfortunately, perianal fistulizing Crohn's disease is notoriously difficult to cure with 37% of patients experiencing refractory disease. As a result, patients cycle through numerous immunosuppressive medications that can have significant side effects, and >90% undergo multiple surgical interventions putting them at risk of incontinence.

The specific rationale for MSCs in perianal Crohn's fistulas is based upon 1) their anti-inflammatory and immunomodulatory properties; 2) several studies reporting the safety and efficacy of MSCs for the treatment of perianal Crohn's fistula; 3) existence of safe manufacturing methods for isolation and expansion of MSCs.

This study will enroll 20 participants that have Crohn's disease with medically and surgically refractory perianal fistulizing disease. Participants enrolled will be those that meet particular criteria for participation in the clinical trial.

Enrolled participants will be randomized to treatment group with adult allogeneic bone marrow derived mesenchymal stem cells, versus placebo in a 3:1 fashion. Participants in the treatment group will have a direct injection of MSCs at a dose of 75 million cells. This will be given as a direct injection in and around the fistula tract. Participants will be evaluated for complete healing at three months. If complete healing has been achieved, participants will continue to be followed for one year. If complete healing has not been achieved at three months, participants will be eligible for a second injection of MSCs at the same dose of 75 million cells. Control participants without complete healing from placebo will cross over at the 6 month visit to receive an injection of MSCs and again three months after this as above, and will be followed for one year after treatment to a total duration of 18 months.

Conditions

Perianal Crohn Disease; Perianal Fistula; Crohn Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Mesenchymal Stem Cells

Direct injection of adult allogeneic bone marrow derived mesenchymal stem cells, at a dose of 75 million cells into perianal fistula(s) at baseline with a possible repeat injection at 3 months if not completely healed from the first injection.

Group Type: EXPERIMENTAL

Mesenchymal Stem Cells

Intervention Type: DRUG

Direct injection of adult allogeneic bone marrow derived mesenchymal stem cell product, at a dose of 75 million cells into perianal fistula(s)

Placebo

Direct injection of normal saline. If not completely healed after 6 months, participants will then cross over to the treatment group to receive a direct injection of adult allogeneic bone marrow derived mesenchymal stem cells, at a dose of 75 million cells into perianal fistula(s)

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Normal saline

Interventions

Mesenchymal Stem Cells

Direct injection of adult allogeneic bone marrow derived mesenchymal stem cell product, at a dose of 75 million cells into perianal fistula(s)

Intervention Type: DRUG

Placebo

Normal saline

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. Men and Women 18-75 years of age with a diagnosis of Crohn's disease for at least six months duration.

2. Single and Multi-tract Perianal fistula, with or without previous failed surgical repair.

3. Have no contraindications to MR evaluations: e.g. pacemaker or magnetically active metal fragments, claustrophobia

4. Ability to comply with protocol

5. Competent and able to provide written informed consent

6. Concurrent Crohn's-related therapies with stable doses (>2 months) corticosteroids, 5- ASA drugs, immunomodulators, anti-TNF therapy, anti-integrin and anti-interleukin therapies are permitted

Exclusion Criteria

1. Inability to give informed consent.

2. 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 subject.

3. Specific exclusions:

1. Hepatitis B or C

2. HIV

3. Abnormal AST or ALT at screening(defined as >/= 2x ULN)

4. History of cancer including melanoma (with the exception of localized skin cancers) within one year of screening.

5. History of colorectal cancer within 5 years

6. Investigational drug within one month of treatment

7. Pregnant or breast feeding or trying to become pregnant.

8. Presence of a rectovaginal or perineal body fistula

9. Change in Crohn's immunosuppressive regimen within the 2 months prior to enrollment

10. Uncontrolled intestinal Crohn's disease which will require escalation for medical therapy or surgery within 2 months of enrollment

11. Severe anal canal disease that is stenotic and requires dilation

12. Female participant unwilling to agree to use acceptable contraception methods during participation in study

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Amy Lightner

OTHER

Sponsor Role: lead

Responsible Party

Amy Lightner

Sponsor-Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Amy Lightner, MD

Role: PRINCIPAL_INVESTIGATOR

The Cleveland Clinic

Locations

Cleveland Clinic

Cleveland, Ohio, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Allison Bayles, AA

Role: CONTACT

ibdstemcelltherapy@ccf.org

216-444-0887

Alex VanDenBossche, BSN

Role: CONTACT

ibdstemcelltherapy@ccf.org

216-379-0307

Facility Contacts

Allison Bayles

Role: primary

Alex VanDenBossche

Role: backup

References

Kasparek MS, Glatzle J, Temeltcheva T, Mueller MH, Koenigsrainer A, Kreis ME. Long-term quality of life in patients with Crohn's disease and perianal fistulas: influence of fecal diversion. Dis Colon Rectum. 2007 Dec;50(12):2067-74. doi: 10.1007/s10350-007-9006-5.

Reference Type: BACKGROUND

PMID: 17680311 (View on PubMed)

Sandborn WJ, Fazio VW, Feagan BG, Hanauer SB; American Gastroenterological Association Clinical Practice Committee. AGA technical review on perianal Crohn's disease. Gastroenterology. 2003 Nov;125(5):1508-30. doi: 10.1016/j.gastro.2003.08.025. No abstract available.

Reference Type: BACKGROUND

PMID: 14598268 (View on PubMed)

Schwartz DA, Loftus EV Jr, Tremaine WJ, Panaccione R, Harmsen WS, Zinsmeister AR, Sandborn WJ. The natural history of fistulizing Crohn's disease in Olmsted County, Minnesota. Gastroenterology. 2002 Apr;122(4):875-80. doi: 10.1053/gast.2002.32362.

Reference Type: BACKGROUND

PMID: 11910338 (View on PubMed)

Panes J, Garcia-Olmo D, Van Assche G, Colombel JF, Reinisch W, Baumgart DC, Dignass A, Nachury M, Ferrante M, Kazemi-Shirazi L, Grimaud JC, de la Portilla F, Goldin E, Richard MP, Leselbaum A, Danese S; ADMIRE CD Study Group Collaborators. Expanded allogeneic adipose-derived mesenchymal stem cells (Cx601) for complex perianal fistulas in Crohn's disease: a phase 3 randomised, double-blind controlled trial. Lancet. 2016 Sep 24;388(10051):1281-90. doi: 10.1016/S0140-6736(16)31203-X. Epub 2016 Jul 29.

Reference Type: BACKGROUND

PMID: 27477896 (View on PubMed)

Panes J, Garcia-Olmo D, Van Assche G, Colombel JF, Reinisch W, Baumgart DC, Dignass A, Nachury M, Ferrante M, Kazemi-Shirazi L, Grimaud JC, de la Portilla F, Goldin E, Richard MP, Diez MC, Tagarro I, Leselbaum A, Danese S; ADMIRE CD Study Group Collaborators. Long-term Efficacy and Safety of Stem Cell Therapy (Cx601) for Complex Perianal Fistulas in Patients With Crohn's Disease. Gastroenterology. 2018 Apr;154(5):1334-1342.e4. doi: 10.1053/j.gastro.2017.12.020. Epub 2017 Dec 24.

Reference Type: BACKGROUND

PMID: 29277560 (View on PubMed)

Molendijk I, Bonsing BA, Roelofs H, Peeters KC, Wasser MN, Dijkstra G, van der Woude CJ, Duijvestein M, Veenendaal RA, Zwaginga JJ, Verspaget HW, Fibbe WE, van der Meulen-de Jong AE, Hommes DW. Allogeneic Bone Marrow-Derived Mesenchymal Stromal Cells Promote Healing of Refractory Perianal Fistulas in Patients With Crohn's Disease. Gastroenterology. 2015 Oct;149(4):918-27.e6. doi: 10.1053/j.gastro.2015.06.014. Epub 2015 Jun 25.

Reference Type: BACKGROUND

PMID: 26116801 (View on PubMed)

Molendijk I, van der Meulen-de Jong AE, Verspaget HW, Veenendaal RA, Hommes DW, Bonsing BA, Peeters KCMJ. Standardization of mesenchymal stromal cell therapy for perianal fistulizing Crohn's disease. Eur J Gastroenterol Hepatol. 2018 Oct;30(10):1148-1154. doi: 10.1097/MEG.0000000000001208.

Reference Type: BACKGROUND

PMID: 30095479 (View on PubMed)

Other Identifiers

20-1020

Identifier Type: -

Identifier Source: org_study_id