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

Mesoblast

Status and phase: Completed; Phase 3

Conditions: Crohn's Disease

Treatments: Drug: Prochymal®; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT00482092

CRD 603

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 330 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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330 participants in 3 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Participants will receive matching placebo administered as intravenous (IV) infusions.

Treatment:

Drug: Placebo

Prochymal® - Low dose

Active Comparator group

Description:

Participants will receive a total dose of Prochymal® 600 x 10\^6 cells, IV infusion, on four days, once daily.

Treatment:

Drug: Prochymal®

Prochymal® - High dose

Active Comparator group

Description:

Participants will receive a total dose of Prochymal® 1200 x 10\^6 cells, IV infusion, on four days, once daily.

Treatment:

Drug: Prochymal®