Pediatric MSC-AFP Sub-study for Crohn's Fistula

Study Overview
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Brief Summary
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The purpose of this study is to determine the safety of using an autologous mesenchymal stromal cell (MSC) coated fistula plug in people with fistulizing Crohn's disease. Autologous means these cells to coat the plug come from the patient.

Detailed Description
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The investigators propose to study the safety of autologous mesenchymal stromal cell transfer using a biomatrix (the Gore Bio-A Fistula Plug) in a Phase I study using a single dose of 20 million cells. 5 patients (age 12 to 17 years) with Crohn's perianal fistulas will be enrolled. Subjects will undergo standard adjuvant therapy including drainage of infection and placement of a draining seton. Six weeks post placement of the draining seton, the seton will be replaced with the MSC loaded Gore fistula plug as per current clinical practice. The subjects will be subsequently followed for fistula response and closure for 24 months. This is an autologous product derived from the patient and used only for the same patient.

Official Title
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A Phase I Study of Autologous Mesenchymal Stromal Cell Coated Fistula Plug in Patients With Fistulizing Crohn's Disease: Pediatric Sub-study

Conditions
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Fistula in Ano, Crohn Disease

Intervention / Treatment
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* Drug: MSC-AFP


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Males and females 12-17 years of age. Residents of the United States. Crohn's disease with single or multiple draining complex perianal fistulae (definition as below) for at least three months despite standard therapy (definition below). Concurrent therapies with corticosteroids, 5-aminosalicylate (5-ASA) drugs, thiopurines, methotrexate (MTX), antibiotics, and anti-tumor necrosis factor (TNF) therapy are permitted. All patients should have undergone a colonoscopy in last 12 months to rule out malignant or premalignant condition 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 (and assent where appropriate). Must have failed standard medical therapy including anti-TNF agents Exclusion Criteria Inability to obtain informed consent (and assent where appropriate). Clinically significant medical conditions within the six months before administration of MSCs: e.g. sepsis, pneumonia active serious infection or other conditions that would, in the opinion of the investigators, compromise the safety of the patient. Specific exclusions; a. Evidence of hepatitis B, C, or HIV History of cancer including melanoma (with the exception of localized skin cancers) Investigational drug within thirty (30) days of baseline A resident outside the United States Pregnant or trying to become pregnant, or breast feeding. History of clinically significant auto-immunity (other than Crohn's disease) or any previous example of fat-directed autoimmunity Previous allergic reaction to a perianal fistula plug. If adipose tissue is not technically feasible Weight less than 35 kg Allergic to local anesthetics Non-enterocutaneous tracts (i.e. recto-vaginal, entero-vesicular)

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MSC-AFP<br>This is a single treatment group study. All patients will receive treatment of a stem cell coated fistula plug. | Drug: MSC-AFP<br>* Patients will have a mesenchymal stromal cell coated anal fistula plug placed in their Crohn's perianal fistula tract.<br>* Other names: mesenchymal stromal cell coated anal fistula plug;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-related adverse events (safety and toxicity) | Participants will have a health assessment and blood work done at each study visit to monitor for adverse events. | 2 months to approximately at 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with response to the treatment regarding cessation of drainage from the treated fistula. | Participants will have a clinical assessment of fistula drainage at each study visit. | 2 months to approximately at 24 months | 
| Number of participants with radiographic response to the treatment regarding the treated fistula. | Participants will have an assessment of healing radiographically by magnetic resonance imaging (MRI) at Week 2 visit, Week 8, and Week 24. | Week 2, Week 8, and Week 24 |