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

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

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.

Study Overview

• Status: Completed
• Conditions: Crohn's Disease
• Intervention / Treatment: Drug: Placebo; Drug: Prochymal®

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.

• Study Type: Interventional
• Enrollment (Actual): 330
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • South Australia
    • Adelaide, South Australia, Australia
      • Royal Adelaide Hospital
  • Victoria
    • Melbourne, Victoria, Australia
      • Royal Melbourne Hospital
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N1
      • University of Calgary
    • Edmonton, Alberta, Canada, T6G 2X8
      • University of Alberta Hospital
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3A 1R9
      • Health Science Centre
  • Ontario
    • London, Ontario, Canada, N6A 5A5
      • London Health Sciences Centre
    • Toronto, Ontario, Canada, M5G 1X5
      • Mount Sinai Hospital
• New Zealand
  • Christchurch, New Zealand
    • University of Otago
  • Hamilton, New Zealand
    • Waikato Hospital
• United States
  • California
    • Los Angeles, California, United States, 90033
      • University of Southern California University Hospital
    • San Francisco, California, United States, 94115
      • University of California, San Francisco
  • Colorado
    • Wheat Ridge, Colorado, United States, 80033
      • Western States Clinical Research
  • Florida
    • Clearwater, Florida, United States, 33765
      • Clinical Research of West Florida
    • Jacksonville, Florida, United States, 32256
      • Borland-Groover Clinic
    • Winter Park, Florida, United States, 32789
      • Shafran Gastroenterology Center
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Atlanta Gastroenterology Associates
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center
    • Urbana, Illinois, United States, 61801
      • Carle Clinic Association
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Medical Center
  • Kansas
    • Topeka, Kansas, United States, 66606
      • Cotton-O'Neil Clinical Research Center
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky Hospital
    • Louisville, Kentucky, United States, 40202
      • University of Louisville Hospital
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808
      • Gulf Coast Research
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland, Baltimore
    • Bethesda, Maryland, United States, 20892
      • National Institutes of Health
    • Chevy Chase, Maryland, United States, 20815
      • Chevy Chase Clinical Research
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02115
      • Brigham and Womens Hospital
    • Worcester, Massachusetts, United States, 01610
      • Clinical Pharmacology Study Group
  • Michigan
    • Dearborn, Michigan, United States, 48124
      • Center for Clinical Studies
    • Troy, Michigan, United States, 48098
      • Center for Digestive Health
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota Hospital
  • Missouri
    • Saint Louis, Missouri, United States, 63128
      • St Louis Center for Clinical Studies
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Medical Center
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai School of Medicine
    • New York, New York, United States, 10028
      • Weill Cornell Medical College
    • Rochester, New York, United States, 14621
      • Rochester General Hospital
    • Rochester, New York, United States, 14607
      • Rochester Institute for Digestive Diseases
    • Stony Brook, New York, United States, 11794
      • University Hospital and Medical Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28207
      • Charlotte Gastroenterology and Hepatology
    • Pinehurst, North Carolina, United States, 28734
      • Pinehurst Medical Clinic
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74135
      • Gastroenterology United of Tulsa
    • Tulsa, Oklahoma, United States, 74137
      • Options Health Research
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheney Center for Digestive Health
  • Tennessee
    • Germantown, Tennessee, United States, 37138
      • Gastroenterology Center Of The Midsouth
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
    • Nashville, Tennessee, United States, 37205
      • Nashville GI Specialists
  • Texas
    • Dallas, Texas, United States, 75246
      • Baylor University Medical Center
    • Galveston, Texas, United States, 77555
      • University of Texas Medical Branch
    • Houston, Texas, United States, 77030
      • University of Texas Health Science Center
  • Vermont
    • Burlington, Vermont, United States, 05401
      • University of Vermont
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Digestive and Liver Disease Specialists
    • Richmond, Virginia, United States, 23249
      • McGuire Research Institute
  • Washington
    • Seattle, Washington, United States, 98133
      • Seattle Gastroenterology Associates

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Mesoblast, Inc.
• Investigators: Study Director: Mahboob Rahman, MD, Mesoblast, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): September 17, 2007
• Primary Completion (Actual): September 15, 2014
• Study Completion (Actual): September 15, 2014

Study Registration Dates

• First Submitted: May 30, 2007
• First Submitted That Met QC Criteria: May 31, 2007
• First Posted (Estimate): June 4, 2007

Study Record Updates

• Last Update Posted (Actual): January 13, 2022
• Last Update Submitted That Met QC Criteria: January 11, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: Crohn's disease; adult stem cell therapy
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease; Anti-Infective Agents; Antiviral Agents; Anti-Inflammatory Agents; Remestemcel-l
• Other Study ID Numbers: CRD 603

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No