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

NCT01240915 | Completed Phase 2 Results DMC

• 2 other identifiers: B30410012010-022766-27
• Study Type: interventional
• Target: 105
• Locations: 8 countries
• Sites: 58

Brief Summary

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.

Conditions

Colitis, Ulcerative

Keywords

safety efficacy MultiStem(r) moderate to severe Ulcerative Colitis

Outcome Measures

Primary Outcomes (6)

• Change From Baseline in Endoscopic Score (as Measured by Modified Baron Score) at Week 8

  Modified Baron Score is an instrument designed to measure endoscopic activity of ulcerative colitis. It classifies the mucosal inflammation in 4 grades (0=normal, 1=granular mucosa with an abnormal vascular pattern, 2=friable mucosa, 3=microulceration with spontaneous bleeding, 4=gross ulceration with spontaneous bleeding).

  Baseline and Week 8

• Change From Baseline in Rectal Bleeding Mayo Subscore at Week 4

  Mayo Score is an instrument designed to measure disease activity of ulcerative colitis. Mayo subscores for rectal bleeding range from 0 to 3, with higher scores indicating more severe disease.

  Baseline and Week 4

• Change From Baseline in Rectal Bleeding Mayo Subscore at Week 8

  Mayo Score is an instrument designed to measure disease activity of ulcerative colitis. Mayo subscores for rectal bleeding range from 0 to 3, with higher scores indicating more severe disease.

  Baseline and Week 8

• Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

  An AE was any untoward medical occurrence in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pre-treatment state. AEs included both SAEs and non-SAEs.

  Baseline up to Week 52

• Number of Participants With Treatment-Emergent AEs by System Organ Class (SOC)

  Baseline up to Week 52

• Number of Treatment-Emergent AEs by Severity

  The intensity grades were defined as follows: mild=does not interfere with participant's usual function; moderate=interferes to some extent with participant's usual function; severe=interferes significantly with participant's usual function.

  Baseline up to Week 52

Secondary Outcomes (15)

• Change From Baseline in Rectal Bleeding Mayo Subscore at Week 12 and Week 16

  Baseline, Week 12, Week 16

• Number of Participants With Laboratory Test Abnormalities

  Baseline up to Week 24

• Number of Participants With Potentially Clinically Significant Vital Signs Findings

  Baseline up to Week 52

• Fold Change From Baseline in Fecal Calprotectin at Weeks 4, 8, 12, and 16

  Baseline, Weeks 4, 8, 12 and 16

• Fold Change From Baseline in C-Reactive Protein (CRP) at Weeks 4, 8, 12, and 16

  Baseline, Weeks 4, 8, 12 and 16

Study Arms (3)

Cohort 1

EXPERIMENTAL

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; Drug: MultiStem low dose

Cohort 2

EXPERIMENTAL

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; Drug: MultiStem high dose

Cohort 3

EXPERIMENTAL

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; Drug: MultiStem high dose

Interventions

placebo DRUG

once every 7 days for 1- 3 doses

Cohort 1

MultiStem low dose DRUG

1-3 doses

Cohort 1

MultiStem high dose DRUG

Single dose Day 1

Cohort 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pfizer: lead
• Healios K.K.: collaborator

Study Sites (58)

University of California San Francisco

San Francisco, California, 94115, United States

Location

USCF Endoscopy Unit at Mount Zion

San Francisco, California, 94115, United States

Location

Clinical Research of the Rockies

Lafayette, Colorado, 80026, United States

Location

Rocky Mountain Gastroenterology Associates, LLC

Lakewood, Colorado, 80215, United States

Location

Arapahoe Gastroenterology, PC

Littleton, Colorado, 80120, United States

Location

Metropolitan Gastroenterology Group, PC

Washington D.C., District of Columbia, 20006, United States

Location

Gastroenterology Consultants of Clearwater

Clearwater, Florida, 33756, United States

Location

West Coast Endoscopy Center

Clearwater, Florida, 33756, United States

Location

Clinical Research of West Florida, Inc.

Clearwater, Florida, 33765, United States

Location

Borland-Groover Clinic

Jacksonville, Florida, 32256, United States

Location

Jacksonville Center for Endoscopy

Jacksonville, Florida, 32256, United States

Location

Miami Research Associates

South Miami, Florida, 33143, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Cotton-O'Neil Clinical Research Center, Digestive Health

Topeka, Kansas, 66606, United States

Location

University of Louisville Healthcare Outpatient Center

Louisville, Kentucky, 40202, United States

Location

University of Louisville Hospital

Louisville, Kentucky, 40202, United States

Location

Metropolitan Gastroenterology Group, PC - Chevy Chase Clinical Research

Chevy Chase, Maryland, 20815, United States

Location

Endoscopic Microsurgery Associates, PA

Towson, Maryland, 21204, United States

Location

Clinical Research Institute of Michigan, LLC

Chesterfield, Michigan, 48047, United States

Location

Center for Digestive Health

Troy, Michigan, 48098, United States

Location

Utica Surgery Center

Utica, Michigan, 48317, United States

Location

Surgery Center of Columbia

Columbia, Missouri, 65201, United States

Location

Center for Digestive and Liver Diseases, Inc.

Mexico, Missouri, 65265, United States

Location

Present, Chapman, Steinlauf and Marion

New York, New York, 10028, United States

Location

Mount Sinai School of Medicine

New York, New York, 10029, United States

Location

Asher Kornbluth, MD PC

New York, New York, 10128, United States

Location

Charlotte Gastroenterology and Hepatology, PLLC

Charlotte, North Carolina, 28207, United States

Location

Wake Internal Medicine Consultants, Inc.

Raleigh, North Carolina, 27612, United States

Location

Wake Research Associates

Raleigh, North Carolina, 27612, United States

Location

Wake Forest University University Baptist Medical Center - Internal Medicine

Winston-Salem, North Carolina, 27157, United States

Location

Gastro One

Germantown, Tennessee, 38138, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232-1375, United States

Location

Digestive and Liver Disease Specialists

Norfolk, Virginia, 23502, United States

Location

Sentara Leigh Hospital

Norfolk, Virginia, 23502, United States

Location

Sentara Norfolk General Hospital

Norfolk, Virginia, 23507, United States

Location

McGuire DVAMC

Richmond, Virginia, 23249, United States

Location

University of Washington Medical Center

Seattle, Washington, 98195, United States

Location

Hopital Erasme / Gastroenterology

Brussels, 1070, Belgium

Location

Pfizer Clinical Research Unit

Brussels, 1070, Belgium

Location

University of Alberta Hospital

Edmonton, Alberta, T6G 2B7, Canada

Location

Northern Alberta Clinical Trials and Research Center

Edmonton, Alberta, T6G 2C8, Canada

Location

Zeidler Ledcor Centre - University of Alberta

Edmonton, Alberta, T6G 2X8, Canada

Location

Maisonneuve-Rosemont Hospital

Montreal, Quebec, H1T 2M4, Canada

Location

Agaplesion Markus Krankenhaus

Frankfurt am Main, 60431, Germany

Location

Universitaetsklinikum Halle

Halle, 06120, Germany

Location

Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

Szent Janos Korhaz es Eszak-budai Egyesitett Korhazak/I. Belgyogyaszat es Gastroenterologia

Budapest, 1125, Hungary

Location

Pandy Kalman Megyei Korhaz, III. sz. Belosztaly-Gasztroenterologia

Gyula, 5700, Hungary

Location

Karolina Korhaz Rendelointezet, Belgyogyaszat

Mosonmagyaróvár, 9200, Hungary

Location

Tolna Megyei Balassa Janos Korhaz / II. Belgyogyaszat

Szekszárd, 7100, Hungary

Location

Azienda Ospedaliera Luigi Sacco

Milan, 20157, Italy

Location

Azienda Ospedaliera di Padova

Padua, 35128, Italy

Location

Policlinico Universitario Agostino Gemelli

Roma, 00168, Italy

Location

Gastroenterologicke a hepatologicke oddelenie, V. interna klinika LFUK a UN Bratislava, Ruzinov

Bratislava, Slovakia, 826 06, Slovakia

Location

Gastroenterologicka ambulancia, GEA s.r.o.

Trnava, 917 01, Slovakia

Location

Sahlgrenska Universitetssjukhuset Medicinkliniken

Gothenburg, 413 45, Sweden

Location

Karolinska Universitetssjukhuset, GastroCentrum Medicin

Stockholm, 171 76, Sweden

Location

Akademiska sjukhuset, Mag tarmmottagningen

Uppsala, 751 85, Sweden

Location

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Colitis, Ulcerative

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Inflammatory Bowel Diseases; Colonic Diseases; Intestinal Diseases

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 10, 2010
• First Posted: November 15, 2010
• Study Start: February 1, 2011
• Primary Completion: November 1, 2014
• Study Completion: November 1, 2014
• Last Updated: February 23, 2016
• Results First Posted: February 23, 2016

Record last verified: 2016-01

Locations

SL (2); DE (3); CA (4); US (37); IT (3); SE (3); HU (4); BE (2)