A Phase I Study Evaluating Autologous Bone Marrow Derived Mesenchymal Stromal for Crohn's Disease. (EPIC/MSC/IBD)

A Phase I Study Evaluating Safety and Tolerability of Autologous Bone Marrow Derived Mesenchymal Stromal (MSC) Cells in Adults With Moderate to Severe Crohn's Disease.

In this Phase I trial the investigators intend to show safety and tolerability of autologous MSC, expanded using a non-xenogeneic, human component platelet lysate expansion media. Fresh, non cryopreserved, autologous MSCs will delivered intravenously as a single bolus dose in a dose escalation phase I study. The investigators intend to test whether the product is clinically safe in adults (18-65 years old) with CD and to determine maximal deliverable dose. Secondary endpoint will monitor effectiveness using CDAI as an endpoint.

Study Overview

• Status: Completed
• Conditions: Crohn's Disease
• Intervention / Treatment: Biological: autologous mesenchymal stromal cell

Detailed Description

EPIC MSC/IBD is made up of autologous marrow-derived mesenchymal stromal cells ex vivo expanded numerically for approximately 14 days using pooled human Platelet Lysate (phPL), harvested on the day of infusion, washed and suspended at a concentration of 4 million cells/ml in Plasmalyte A with 0.5% human serum albumin. This is a phase I dose-escalation, open label, non-randomized, non-placebo controlled, single group assignment study to evaluate the safety and tolerability of a single intravenous infusion of EPIC MSC2011-001. EPIC EPIC MSC/IBD will be infused intravenously and will be administered at one of three dose levels: (Tier 1) 2 million cells/kg patient body weight; (Tier 2) 5 million cells/kg, and (Tier 3) 10 million cells/kg. This Phase I clinical trial will enroll 16-20 subjects with moderate to severe Crohn's. The duration of this study for each patient is 12 weeks. The investigators anticipate that this study will be completed within 2 years of commencement.

Primary objective: To describe and compare the safety and tolerability of a single infusion of fresh autologous bone marrow derived Mesenchymal stromal cells infused to patients with moderate to severe Crohn's disease.

Secondary objective: Efficacy of autologous bone marrow derived Mesenchymal stromal cells infusion to patients with moderate to severe Crohn's disease as assessed through disease activity index, and quality of life index.

Safety variables:Adverse events (AEs),Laboratory parameters (hematology, biochemistry, urinalysis), Vital signs.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

• Men and women 18-65 years of age.
• Patient must have had CD for at least 3 months from the time of initial diagnosis. The diagnosis of CD must have been confirmed by endoscopic and histological evidence.
• Patients must have active Crohn's disease as defined by a Crohns Disease Activity Index (CDAI) score between >220 at screening and baseline.
• Patients should have no need for immediate surgery (i.e. due to obstruction, strictures, active abscess or perforations ).
• Subjects must be refractory (defined as lack of response for at least 3 months) to immunomodulators (including 6-mercaptopurine and azathioprine and methotrexate) or anti-TNF therapy at present or some point in the course of their disease. Lack of response is defined by failure to reduce the CDAI score by at least 70 points.
• The following medications will be allowed: mesalamine and prednisone (stable dose for at least 2 weeks prior to enrollment).
• Subjects on anti TNF therapy will require a minimum of 4 weeks washout period prior to screening.
• Subjects on non-steroidal analgesics require a minimum of 2 weeks washout period prior to screening
• If female and of child-bearing age, patient must be non-pregnant, non-breastfeeding, and use adequate contraception;
• Patient is willing to participate in the study and has signed the informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: autologous mesenchymal stromal cells	Biological: autologous mesenchymal stromal cell

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of adverse events	Monitoring for adverse events at time of MSC infusion and in 12 months following	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Crohn's disease activity Index (CDAI)	CDAI score before and after intervention will be monitored over 12 months	12 months

Collaborators and Investigators

• Sponsor: Emory University
• Collaborators: Atlanta Clinical and Translational Science Institute
• Investigators: Principal Investigator: Tanvi Dhere, MD, Emory University

Publications and helpful links

General Publications

• Dhere T, Copland I, Garcia M, Chiang KY, Chinnadurai R, Prasad M, Galipeau J, Kugathasan S. The safety of autologous and metabolically fit bone marrow mesenchymal stromal cells in medically refractory Crohn's disease - a phase 1 trial with three doses. Aliment Pharmacol Ther. 2016 Sep;44(5):471-81. doi: 10.1111/apt.13717. Epub 2016 Jul 7.

Study record dates

Study Major Dates

• Study Start: July 1, 2012
• Primary Completion (Actual): July 1, 2015

Study Registration Dates

• First Submitted: August 6, 2012
• First Submitted That Met QC Criteria: August 7, 2012
• First Posted (Estimate): August 8, 2012

Study Record Updates

• Last Update Posted (Estimate): October 17, 2016
• Last Update Submitted That Met QC Criteria: October 13, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: Crohn's disease; inflammatory bowel disease
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease
• Other Study ID Numbers: IRB00051454; EPIC001 (Other Identifier: Other)