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

Primary Purpose

Perianal Crohn Disease, Perianal Fistula, Crohn Disease

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Mesenchymal Stem Cells
Placebo
Sponsored by
Amy Lightner
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Perianal Crohn Disease focused on measuring perianal fistula, perianal Crohn's disease, mesenchymal stromal cells, mesenchymal stem cells

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Cleveland ClinicRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Mesenchymal Stem Cells

Placebo

Arm Description

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.

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)

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Full Information

First Posted
August 17, 2020
Last Updated
April 1, 2022
Sponsor
Amy Lightner
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1. Study Identification

Unique Protocol Identification Number
NCT04519671
Brief Title
Mesenchymal Stem Cells for the Treatment of Perianal Fistulizing Crohn's Disease
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
April 2022
Overall Recruitment Status
Recruiting
Study Start Date
November 19, 2020 (Actual)
Primary Completion Date
November 2022 (Anticipated)
Study Completion Date
November 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Amy Lightner

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Perianal Crohn Disease, Perianal Fistula, Crohn Disease
Keywords
perianal fistula, perianal Crohn's disease, mesenchymal stromal cells, mesenchymal stem cells

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Crossover Assignment
Masking
Participant
Masking Description
Single
Allocation
Randomized
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Mesenchymal Stem Cells
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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)
Intervention Type
Drug
Intervention Name(s)
Mesenchymal Stem Cells
Intervention Description
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
Other
Intervention Name(s)
Placebo
Intervention Description
Normal saline
Primary Outcome Measure Information:
Title
Treatment related adverse events
Description
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
Time Frame
Month 6
Secondary Outcome Measure Information:
Title
Complete clinical healing
Description
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
Time Frame
Month 6, Month 12
Other Pre-specified Outcome Measures:
Title
Partial clinical healing
Description
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
Time Frame
Month 6, Month 12
Title
Lack of response
Description
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
Time Frame
Month 6, Month 12
Title
Worsening of disease
Description
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
Time Frame
Month 6, Month 12

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria Men and Women 18-75 years of age with a diagnosis of Crohn's disease for at least six months duration. Single and Multi-tract Perianal fistula, with or without previous failed surgical repair. Have no contraindications to MR evaluations: e.g. pacemaker or magnetically active metal fragments, claustrophobia Ability to comply with protocol Competent and able to provide written informed consent 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 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 subject. Specific exclusions: Hepatitis B or C HIV Abnormal AST or ALT at screening(defined as >/= 2x ULN) History of cancer including melanoma (with the exception of localized skin cancers) within one year of screening. History of colorectal cancer within 5 years Investigational drug within one month of treatment Pregnant or breast feeding or trying to become pregnant. Presence of a rectovaginal or perineal body fistula Change in Crohn's immunosuppressive regimen within the 2 months prior to enrollment Uncontrolled intestinal Crohn's disease which will require escalation for medical therapy or surgery within 2 months of enrollment Severe anal canal disease that is stenotic and requires dilation Female participant unwilling to agree to use acceptable contraception methods during participation in study
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Allison Bayles, AA
Phone
216-444-0887
Email
ibdstemcelltherapy@ccf.org
First Name & Middle Initial & Last Name or Official Title & Degree
Alex VanDenBossche, BSN
Phone
216-379-0307
Email
ibdstemcelltherapy@ccf.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Amy Lightner, MD
Organizational Affiliation
The Cleveland Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Allison Bayles
First Name & Middle Initial & Last Name & Degree
Alex VanDenBossche

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
17680311
Citation
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.
Results Reference
background
PubMed Identifier
14598268
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. doi: 10.1016/j.gastro.2003.08.025. No abstract available.
Results Reference
background
PubMed Identifier
11910338
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. doi: 10.1053/gast.2002.32362.
Results Reference
background
PubMed Identifier
27477896
Citation
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.
Results Reference
background
PubMed Identifier
29277560
Citation
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.
Results Reference
background
PubMed Identifier
26116801
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.
Results Reference
background
PubMed Identifier
30095479
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.
Results Reference
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Mesenchymal Stem Cells for the Treatment of Perianal Fistulizing Crohn's Disease

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