An Australian Study of Mesenchymal Stromal Cells for Crohn's Disease

A Multicentre Australian Phase 2 Study to Evaluate Safety and Efficacy of Mesenchymal Stromal Cells for Treating Biologic Refractory Crohn's Disease

Despite the advent of newer biologic therapies such as infliximab for Crohn's disease, a form of autoimmune inflammatory bowel disease, a proportion of patients are refractory to such therapy and require surgery. The hypothesis is that mesenchymal stromal cell therapy using third party human cultured cells will be safe and effective

Study Overview

• Status: Completed
• Conditions: Crohn Disease
• Intervention / Treatment: Drug: Mesenchymal stromal cells (MSC) for infusion

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Western Australia
    • Perth, Western Australia, Australia, 6000
      • Department of Gastroenterology and Hepatology, Royal Perth Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Colonic or small bowel Crohn's disease based on endoscopic appearances and histology
• Refractory to induction with infliximab or adalimumab; or have lost response to these agents; or have had side effects precluding their further use
• Where there has been loss of response to one of these agents, the other must be tried before being eligible
• Crohn's disease activity score (CDAI) 250 or more.
• C-reactive protein >10mg/L
• Surgery must have been offered to the subject (if appropriate) and declined
• Signed informed consent

Exclusion Criteria:

• Active sepsis, perforating disease. Coexistent perianal fistulous disease is permitted, providing no co-existent infection within previous 4 weeks
• Chronic stricturing disease in isolation
• Coexistent CMV disease
• Prior history of malignancy
• Pregnant or unwilling to practice contraceptive therapy or breast feeding females
• Last biologic therapy must be greater than 4 weeks prior, must be on stable corticosteroid dose for 14 days prior, during therapy and for 14 days after therapy, must be on stable immunomodulator dose (eg, azathioprine) for 14 days prior, during therapy and for 14 days after.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mesenchymal stromal cells; Mesenchymal stromal cells administered weekly for 4 weeks	Drug: Mesenchymal stromal cells (MSC) for infusion; MSC 2X10E6/kg recipient weight are infused over 15 minutes intravenously weekly for 4 weeks; Other Names: No other names

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical response to MSC: Reduction of Crohn's disease Activity score by 100 points or more at six weeks post start of therapy	Colonoscopy and biopsy as well as clinical parameters used for the Crohn's disease acivity (www.ibdaustralia.org/cdai/) will be undertaken at screening pre-therapy and at 6 weeks after start of therapy.	Six weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of infusional toxicity	Subjects will receive mesenchymal stromal cell therapy, 2X10E6/kg weekly by IV infusion for 4 weeks and will be assessed for 4 hours post infusion	Six weeks
Induction of remission	Crohn's disease activity index assessed as below 150	Six weeks
Improved quality of life	Increase in IBDQ and SF-36 scores measured at six weeks	Six weeks
Endoscopic improvement.	Crohn's disease endoscopic improvement score will be measured at repeat endoscopy six weeks after start of treatment	Six weeks

Collaborators and Investigators

• Sponsor: R.P.Herrmann
• Collaborators: The Alfred; The Queen Elizabeth Hospital; Concord Hospital; Sir Charles Gairdner Hospital
• Investigators: Principal Investigator: Geoff Forbes, MD, Royal Perth Hospital

Publications and helpful links

General Publications

• Forbes GM, Sturm MJ, Leong RW, Sparrow MP, Segarajasingam D, Cummins AG, Phillips M, Herrmann RP. A phase 2 study of allogeneic mesenchymal stromal cells for luminal Crohn's disease refractory to biologic therapy. Clin Gastroenterol Hepatol. 2014 Jan;12(1):64-71. doi: 10.1016/j.cgh.2013.06.021. Epub 2013 Jul 19.

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (Actual): June 1, 2014
• Study Completion (Actual): June 1, 2015

Study Registration Dates

• First Submitted: March 22, 2010
• First Submitted That Met QC Criteria: March 22, 2010
• First Posted (Estimate): March 23, 2010

Study Record Updates

• Last Update Posted (Estimate): June 9, 2015
• Last Update Submitted That Met QC Criteria: June 7, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Keywords: mesenchymal stromal cells; colitis; ileitis
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease
• Other Study ID Numbers: EC2009/123; CTN2010/0098 (Other Identifier: Therapeutics Good Administration, Government of Australia)