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

Purpose

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.

Condition	Intervention	Phase
Colitis, Ulcerative	Drug: placebo Drug: MultiStem low dose Drug: MultiStem high dose	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Phase 2 Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Multi-Center Study To Investigate The Safety And Efficacy Of Multistem(r) (PF-05285401) In Subjects With Moderate To Severe Ulcerative Colitis

Resource links provided by NLM:

Genetics Home Reference related topics: ulcerative colitis

MedlinePlus related topics: Endoscopy Ulcerative Colitis

U.S. FDA Resources

Further study details as provided by Pfizer:

Primary Outcome Measures:

Incidence and severity of adverse events (at Weeks 4, 8, 12 and 16). [ Time Frame: 16 weeks ] [ Designated as safety issue: Yes ]
Change from baseline of endoscopic score at Week 8 as measured by modified Baron score. [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
Change from baseline of Mayo rectal bleeding sub-score at Week 4. [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
Change from baseline of Mayo rectal bleeding sub-score at Week 8. [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Changes in laboratory measurements of safety and vital signs (at Weeks 4, 8, 12 and 16). [ Time Frame: 16weeks ] [ Designated as safety issue: Yes ]
Change from baseline of Mayo rectal bleeding sub-score at Weeks 12 and 16. [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
Changes from baseline at Weeks 4, 8, 12 and 16, in the following biomarker levels: fecal calprotectin, CRP. [ Time Frame: 16weeks ] [ Designated as safety issue: No ]
Proportions of subjects with a Mayo rectal bleeding sub-score equal 0 at Weeks 4, 8, 12 and 16. [ Time Frame: 8,16weeks ] [ Designated as safety issue: No ]
Proportion of subjects in endoscopic remission at Week 8 (defined as subjects with a modified Baron endoscopic score equal 0). [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
Proportion of subjects in clinical remission at Week 8 (defined as a total Mayo score of 2 points or lower, with no individual sub-score exceeding 1 point). [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
Proportions of subjects with a decrease from baseline of at least one point in Mayo rectal bleeding sub-score at Weeks 4, 8, 12 and 16. [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
Proportion of subjects with an endoscopic response at Week 8 (defined as a decrease in modified Baron endoscopic score from baseline of at least 2 points). [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
Proportion of subjects with a clinical response at Week 8 (defined as a decrease in total Mayo score from baseline in Mayo score of at least 3 points and at least 30 percent, with an accompanying decrease in the sub-score for rectal bleeding of at least [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
1 point or an absolute sub-score for rectal bleeding of 0 or 1). [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
Change from baseline in total Mayo score at Week 8. [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
Changes from baseline in partial Mayo score at Weeks 4, 8, 12 and 16. [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
Patient-reported rectal bleeding scores, to be modeled longitudinally up to and including Week 16. [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
Changes in biopsy histology score at Week 8 (measured by Riley Index). [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment:	128
Study Start Date:	February 2011
Estimated Study Completion Date:	October 2014
Estimated Primary Completion Date:	January 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Cohort 1 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).	Drug: placebo once every 7 days for 1- 3 doses Drug: MultiStem low dose 1-3 doses Drug: placebo Single dose at week 8 Drug: MultiStem low dose Single dose at week 8
Experimental: Cohort 2 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.	Drug: placebo Single dose Day 1 Drug: MultiStem high dose Single dose Day 1 Drug: placebo Single dose at week 8 Drug: MultiStem high dose Single dose at week 8
Experimental: Cohort 3 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.	Drug: placebo Single dose Day 1 Drug: MultiStem high dose Single dose Day 1 Drug: placebo Single dose at week 8 Drug: MultiStem high dose Single dose at week 8

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01240915

Contacts

Contact: Pfizer CT.gov Call Center

1-800-718-1021

Show 60 Study Locations

Sponsors and Collaborators

Pfizer

Athersys, Inc

Investigators

Study Director:

Pfizer CT.gov Call Center

Pfizer

More Information

Additional Information:

To obtain contact information for a study center near you, click here. This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Pfizer
ClinicalTrials.gov Identifier:	NCT01240915 History of Changes
Other Study ID Numbers:	B3041001
Study First Received:	November 10, 2010
Last Updated:	June 13, 2013
Health Authority:	United States: Food and Drug Administration

Keywords provided by Pfizer:

safety efficacy MultiStem(r) moderate to severe Ulcerative Colitis

Additional relevant MeSH terms:

Colitis
Colitis, Ulcerative
Ulcer
Gastroenteritis
Gastrointestinal Diseases

Digestive System Diseases
Colonic Diseases
Intestinal Diseases
Inflammatory Bowel Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on June 18, 2013