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

Crohn Disease Clinical Trial

— PFCD  

Official title:

A Phase IB/IIA Study of Adult Allogeneic Bone Marrow Derived Mesenchymal Stem Cells for the Treatment of Perianal Fistulizing Crohn's Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04519671
• Other study ID #: 20-1020
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: November 19, 2020
• Est. completion date: November 2022

Study information

• Verified date: April 2022
• Source: The Cleveland Clinic
• Contact: Allison Bayles, AA
• Phone: 216-444-0887
• Email: ibdstemcelltherapy[@]ccf.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: November 2022
• Est. primary completion date: November 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Crohn Disease
• Fistula
• Perianal Crohn Disease
• Perianal Fistula

Intervention

Drug:
• 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)

Other:
• Placebo
Normal saline

Locations

Country	Name	City	State
United States	Cleveland Clinic	Cleveland	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Amy Lightner

Country where clinical trial is conducted

United States, 

References & Publications (7)

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. — View Citation

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. — View Citation

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. — View Citation

Panés J, García-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. — View Citation

Panés J, García-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. — View Citation

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. Review. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Partial clinical healing	Number of participants with partial clinical healing post-injection of 75 million allogeneic bone marrow derived MSC's for the treatment of perianal fistula(s) in the setting of Crohn's disease; Partial clinical healing is defined as: Radiographic Healing: MRI with an absence of a fluid collection >2 cm in 2 of 3 dimensions, lack of edema, inflammation or sign of active inflammatory response. A remnant scar of a fistula tract may remain; Clinical healing: Greater than or equal to 50 % cessation of drainage on both clinical exam with deep palpation and per patient report and epithelization of the external fistula opening	Month 6, Month 12
Other	Lack of response	Number of participants with lack of response post-injection of 75 million allogeneic bone marrow derived MSC's for the treatment of perianal fistula(s) in the setting of Crohn's disease; Lack of response is defined as: Radiographic and Clinical healing which does not meet the threshold for Partial Healing	Month 6, Month 12
Other	Worsening of disease	Number of participants with worsening of disease post-injection of 75 million allogeneic bone marrow derived MSC's for the treatment of perianal fistula(s) in the setting of Crohn's disease; Worsening disease is defined as: Radiographic: MRI with a fluid collection >2 cm in 2 of 3 dimensions, edema, inflammation or sign of active inflammatory response. An increased number of tracts may be seen, or increased branching from the primary tract,; Clinical: Increased drainage per patient report and on clinical exam	Month 6, Month 12
Primary	Treatment related adverse events	Number of participants with treatment related adverse events post-injection of 75 million allogeneic bone marrow derived MSC's for the treatment of perianal fistula(s) in the setting of Crohn's disease as assessed by protocol CCF-Stem Cells IBD-001	Month 6
Secondary	Complete clinical healing	Number of participants with complete clinical healing post-injection of 75 million allogeneic bone marrow derived MSC's for the treatment of perianal fistula(s) in the setting of Crohn's disease.; Complete Healing is defined as: Radiographic Healing: MRI with an absence of a fluid collection >2 cm in 3 of 3 dimensions, lack of edema, inflammation or sign of active inflammatory response. A remnant scar of a fistula tract may remain; Clinical Healing: 100% cessation of drainage on both clinical exam with deep palpation and per patient report and epithelization of the external fistula opening	Month 6, Month 12