Clinical trial NCT00482092: Evaluation of PROCHYMAL® Adult Human Stem Cells for Treatment-resistant Moderate-to-severe Crohn's Disease
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Crohn's Disease
Keywords: Crohn's disease
adult stem cell therapy
Lead sponsor: Mesoblast, Ltd.
Sponsor class: INDUSTRY
First posted: 2007-06-04
Enrollment: 330
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Disease remission (CDAI at or below 150)
timeFrame: 28 days
Secondary outcomes:
measure: Disease improvement (Reduction by at least 100 points in CDAI)
timeFrame: 28 days
measure: Improvement in quality of life (IBDQ)
timeFrame: 28 days
measure: Reduction in number of draining fistulas
timeFrame: 28 days
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of Southern California University Hospital
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Wheat Ridge
country: United States
facility: Western States Clinical Research
state: Colorado
city: Clearwater
country: United States
facility: Clinical Research of West Florida
state: Florida
city: Jacksonville
country: United States
facility: Borland-Groover Clinic
state: Florida
city: Winter Park
country: United States
facility: Shafran Gastroenterology Center
state: Florida
city: Atlanta
country: United States
facility: Atlanta Gastroenterology Associates
state: Georgia
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Urbana
country: United States
facility: Carle Clinic Association
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Medical Center
state: Indiana
city: Topeka
country: United States
facility: Cotton-O'Neil Clinical Research Center
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky Hospital
state: Kentucky
city: Louisville
country: United States
facility: University of Louisville Hospital
state: Kentucky
city: Baton Rouge
country: United States
facility: Gulf Coast Research
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland, Baltimore
state: Maryland
city: Bethesda
country: United States
facility: National Institutes of Health
state: Maryland
city: Chevy Chase
country: United States
facility: Chevy Chase Clinical Research
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Womens Hospital
state: Massachusetts
city: Worcester
country: United States
facility: Clinical Pharmacology Study Group
state: Massachusetts
city: Dearborn
country: United States
facility: Center for Clinical Studies
state: Michigan
city: Troy
country: United States
facility: Center for Digestive Health
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota Hospital
state: Minnesota
city: Saint Louis
country: United States
facility: St Louis Center for Clinical Studies
state: Missouri
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: Rochester
country: United States
facility: Rochester Institute for Digestive Diseases
state: New York
city: Rochester
country: United States
facility: Rochester General Hospital
state: New York
city: Stony Brook
country: United States
facility: University Hospital and Medical Center
state: New York
city: Charlotte
country: United States
facility: Charlotte Gastroenterology and Hepatology
state: North Carolina
city: Pinehurst
country: United States
facility: Pinehurst Medical Clinic
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University
state: North Carolina
city: Tulsa
country: United States
facility: Gastroenterology United of Tulsa
state: Oklahoma
city: Tulsa
country: United States
facility: Options Health Research
state: Oklahoma
city: Pittsburgh
country: United States
facility: Allegheney Center for Digestive Health
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Germantown
country: United States
facility: Gastroenterology Center of the Midsouth
state: Tennessee
city: Nashville
country: United States
facility: Nashville GI Specialists
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: Galveston
country: United States
facility: University of Texas Medical Branch
state: Texas
city: Houston
country: United States
facility: University of Texas Health Science Center
state: Texas
city: Burlington
country: United States
facility: University of Vermont
state: Vermont
city: Norfolk
country: United States
facility: Digestive and Liver Disease Specialists
state: Virginia
city: Richmond
country: United States
facility: McGuire Research Institute
state: Virginia
city: Seattle
country: United States
facility: Seattle Gastroenterology Associates
state: Washington
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Melbourne
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: Winnipeg
country: Canada
facility: Health Science Centre
state: Manitoba
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: Mount Sinai Hospital
state: Ontario
city: Christchurch
country: New Zealand
facility: University of Otago
city: Hamilton
country: New Zealand
facility: Waikato Hospital
Study officials:
affiliation: Mesoblast, Inc.
name: Mahboob Rahman, MD
role: STUDY_DIRECTOR
References: