A Study To Investigate The Safety And Possible Clinical Benefit Of Multistem(r) In Patients With Moderate To Severe Ulcerative Colitis

Pfizer

Status and phase: Completed; Phase 2

Conditions: Colitis, Ulcerative

Treatments: Drug: MultiStem high dose; Drug: placebo; Drug: MultiStem low dose

Study type: Interventional

Funder types: Industry

Identifiers

NCT01240915

B3041001

2010-022766-27 (EudraCT Number)

Details and patient eligibility

About

MultiStem(r) is a new biological product, manufactured from human stem cells obtained from adult bone marrow or other nonembryonic tissue sources. Factors expressed by MultiStem cells are believed to reduce inflammation and regulate immune system function, protect damaged or injured cells and tissue, promote formation of new blood vessels, and augment tissue repair and healing. MultiStem cell treatment resulted in significant efficacy in a mouse model of Graft versus Host Disease with almost complete reversal of gastrointestinal pathology (similar to pathology that would be expected in Ulcerative Colitis). These data, together with safety data generated in 2 other clinical trials, suggest that MultiStem has the potential to be a new treatment option for patients with ulcerative colitis. This is the first study of MultiStem in this patient population and will cautiously explore the safety/toleration and potential benefit of this new treatment in patients with moderate to severe disease.

Enrollment: 105 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Subjects must have a documented diagnosis of ulcerative colitis at least 6 months prior to screening.
• Subjects must have active moderate-to-severe ulcerative colitis based on Mayo score.
• Subjects must have Modified Baron endoscopic score of at least 2 determined within 7 days of first dosing.
• Subjects must have failed or be intolerant (as determined by the investigator) of at least one of the following treatments for UC: Oral corticosteroids, azathioprine or 6-mercaptopurine (6-MP), or anti-tumor necrosis factor (TNF) therapy, eg, infliximab or adalimumab.
• Subjects must be on stable steroid doses.

Exclusion criteria

• Subjects who have abnormal organ and marrow function.
• Subjects with a diagnosis of indeterminate colitis, or clinical findings suggestive of Crohn's disease.
• Subjects who meet Truelove-Witts criteria for severe ulcerative colitis.
• Subjects receiving or who are expected to receive Infliximab or other biologic treatment within 8 weeks of the Day 1 study visit.
• Subjects receiving or who are expected to receive Cyclosporine, mycophenolate, or tacrolimus within 4 weeks of the Day 1 study visit.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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105 participants in 3 patient groups

Cohort 1

Experimental group

Description:

The first 9 subjects will be recruited into Cohort 1 and will receive either placebo (n=3) or MultiStem low dose (n=6) as an intravenous infusion on Day 1. The first five patients enrolled constitute a subgroup of Cohort 1 and these patients will receive multiple doses, once every day for 7 days for 3 doses (Day 1 and Weeks 1 \& 2).

Treatment:

Drug: MultiStem low dose

Drug: MultiStem low dose

Drug: placebo

Drug: placebo

Drug: placebo

Drug: placebo

Drug: placebo

Drug: placebo

Cohort 2

Experimental group

Description:

This group will receive either placebo (n=3) or MultiStem high dose (n=6) as an intravenous infusion on Day 1. The subjects then receive the opposite dose of study medication at Week 8.

Treatment:

Drug: MultiStem high dose

Drug: placebo

Drug: placebo

Drug: MultiStem high dose

Drug: placebo

Drug: placebo

Drug: MultiStem high dose

Drug: placebo

Drug: placebo

Drug: MultiStem high dose

Cohort 3

Experimental group

Description:

These subjects (total n=88 evaluable patients) will receive either Placebo or MultiStem (1:1 randomization) as an intravenous infusion on Day 1. In addition all subjects in Cohort 3 will receive a single infusion of either MultiStem or Placebo at Week 8, depending on their randomization schedule. A total of \~22 patients will receive an additional infusion of MultiStem, \~44 patients will receive the alternative blinded therapy to that which they received for Day 1 infusion, and \~22 patients will receive an additional infusion of placebo.

Treatment:

Drug: MultiStem high dose

Drug: placebo

Drug: placebo

Drug: MultiStem high dose

Drug: placebo

Drug: placebo

Drug: MultiStem high dose

Drug: placebo

Drug: placebo

Drug: MultiStem high dose