Evaluation of PROCHYMAL® Adult Human Stem Cells for Treatment-resistant Moderate-to-severe Crohn's Disease

Study Overview
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Brief Summary
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Protocol 603 is enrolling subjects with moderate-to-severe Crohn's disease who are intolerant to, or have previously failed therapy with, at least one steroid and at least one immunosuppressant and a biologic monoclonal anti-body to tumor necrosis factor alpha. The protocol investigates the safety and efficacy of using PROCHYMAL® adult human stem cells to induce remission. PROCHYMAL is delivered through a vein in the arm four times over two weeks, for approximately an hour each time.

Detailed Description
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A significant number of individuals with Crohn's disease do not find relief with existing steroidal, immunosuppressive, or biologic therapies, and are forced to seek surgery or other drastic measures for treatment. PROCHYMAL® adult human stem cells are manufactured from healthy, volunteer donors, extensively tested, and are stored to be available as needed. Human and animal studies have shown that the cells do not require any donor-recipient matching. The cells may have both immunosuppressive and healing benefits in Crohn's disease. The cells naturally migrate specifically to sites of inflammation, so their effects are believed to be local and self-limiting rather than systemic. Protocol 603 is enrolling subjects to evaluate the ability of PROCHYMAL to induce remission in subjects with moderate-to-severe disease (Crohn's disease activity index -- CDAI -- of between 250 and 450, inclusive) who have failed or been intolerant of at least one drug in each of the steroid, immunosuppressant, and biologic classes.

Official Title
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A Phase III, Multicenter, Placebo-controlled, Randomized, Double-blind Study to Evaluate the Safety and Efficacy of PROCHYMAL® (ex Vivo Cultured Adult Human Mesenchymal Stem Cells) Intravenous Infusion for the Induction of Remission in Subjects Experiencing Treatment-refractory Moderate-to-severe Crohn's Disease

Conditions
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Crohn's Disease

Intervention / Treatment
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* Drug: Prochymal®
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: failed (within last 2 yr) or intolerant of at least one steroid AND at least one immunosuppressant AND at EXACTLY one biologic CDAI between 250 and 450, inclusive endoscopically or radiographically confirmed Crohn's disease of ileus or colon or both C-Reactive Protein Test (CRP) of at least 5 mg/l (0.5 mg/dl)*OR* CDAI of at least 300 weight between 40 and 150 kg, inclusive adequate renal function negative tuberculosis skin (PPD) test (or evaluated low risk of TB activation) Exclusion Criteria: HIV or hepatitis infection active allergy to CT contrast agents, or to bovine or porcine products symptomatic fibrostenotic Crohn's disease permanent ostomy biologic therapy within past 90 d prednisone greater than 20 mg/d within past month short-bowel syndrome total parenteral nutrition abnormal liver function malignancy active within past 5 years (except completely resected basal or squamous cell carcinoma of skin) enteric pathogens, including C. difficile history of colonic mucosal dysplasia current or prior evidence of tuberculosis (TB) (unless risk of activation or re-activation deemed low)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Participants will receive matching placebo administered as intravenous (IV) infusions. | Drug: Placebo<br>* Prochymal® Placebo-matching IV infusion<br>|
| Active Comparator: Prochymal® - Low dose<br>Participants will receive a total dose of Prochymal® 600 x 10^6 cells, IV infusion, on four days, once daily. | Drug: Prochymal®<br>* Prochymal® IV infusion<br>* Other names: Adult Human Mesenchymal Stem Cells;|
| Active Comparator: Prochymal® - High dose<br>Participants will receive a total dose of Prochymal® 1200 x 10^6 cells, IV infusion, on four days, once daily. | Drug: Prochymal®<br>* Prochymal® IV infusion<br>* Other names: Adult Human Mesenchymal Stem Cells;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease remission (CDAI at or below 150) |  | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease improvement (Reduction by at least 100 points in CDAI) |  | 28 days | 
| Improvement in quality of life (IBDQ) |  | 28 days | 
| Reduction in number of draining fistulas |  | 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Crohn's disease, adult stem cell therapy