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

• ClinicalTrials.gov Identifier: NCT00482092
• Recruitment Status: Completed
• First Posted: June 4, 2007
• Last Update Posted: January 13, 2022
• Sponsor: Mesoblast, Inc.
• Information provided by (Responsible Party): Mesoblast, Ltd. ( Mesoblast, Inc. )

Tracking Information

• First Submitted Date: May 30, 2007
• First Posted Date: June 4, 2007
• Last Update Posted Date: January 13, 2022
• Actual Study Start Date: September 17, 2007
• Actual Primary Completion Date: September 15, 2014 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: May 31, 2007): Disease remission (CDAI at or below 150) [ Time Frame: 28 days ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 31, 2007)

• Disease improvement (Reduction by at least 100 points in CDAI) [ Time Frame: 28 days ]
• Improvement in quality of life (IBDQ) [ Time Frame: 28 days ]
• Reduction in number of draining fistulas [ Time Frame: 28 days ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Crohn's Disease

Intervention

• Drug: Prochymal®
  Prochymal® IV infusion
  Other Name: Adult Human Mesenchymal Stem Cells
• Drug: Placebo
  Prochymal® Placebo-matching IV infusion

Study Arms

• Placebo Comparator: Placebo
  Participants will receive matching placebo administered as intravenous (IV) infusions.
  Intervention: Drug: Placebo
• 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.
  Intervention: Drug: Prochymal®
• 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.
  Intervention: Drug: Prochymal®

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 19, 2014): 330
• Original Estimated Enrollment (submitted: May 31, 2007): 258
• Actual Study Completion Date: September 15, 2014
• Actual Primary Completion Date: September 15, 2014 (Final data collection date for primary outcome measure)

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)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Canada, New Zealand, United States

Administrative Information

• NCT Number: NCT00482092
• Other Study ID Numbers: CRD 603
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Mesoblast, Ltd. ( Mesoblast, Inc. )
• Original Responsible Party: Not Provided
• Current Study Sponsor: Mesoblast, Inc.
• Original Study Sponsor: Osiris Therapeutics
• Collaborators: Not Provided

Investigators

• Study Director: Mahboob Rahman, MD; Mesoblast, Inc.

• PRS Account: Mesoblast, Ltd.
• Verification Date: January 2022