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

Colitis, Ulcerative Clinical Trial

Official title:

A Phase 2 Randomized, Double-blind, Placebo-controlled, Parallel Group, Multi-center Study To Investigate The Safety And Efficacy Of Multistem (Pf-05285401) In Subjects With Moderate To Severe Ulcerative Colitis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01240915
• Other study ID #: B3041001
• Secondary ID: 2010-022766-27
• Status: Completed
• Phase: Phase 2
• First received: November 10, 2010
• Last updated: January 26, 2016
• Start date: February 2011
• Est. completion date: November 2014

Study information

• Verified date: January 2016
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 105
• Est. completion date: November 2014
• Est. primary completion date: November 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer

Intervention

Drug:
• placebo
once every 7 days for 1- 3 doses
• MultiStem low dose
1-3 doses
• placebo
Single dose at week 8
• MultiStem low dose
Single dose at week 8
• placebo
Single dose Day 1
• MultiStem high dose
Single dose Day 1
• placebo
Single dose at week 8
• MultiStem high dose
Single dose at week 8
• placebo
Single dose Day 1
• MultiStem high dose
Single dose Day 1
• placebo
Single dose at week 8
• MultiStem high dose
Single dose at week 8

Locations

Country	Name	City	State
Belgium	Hopital Erasme / Gastroenterology	Brussels
Belgium	Pfizer Clinical Research Unit	Bruxelles
Canada	Northern Alberta Clinical Trials and Research Center	Edmonton	Alberta
Canada	University of Alberta Hospital	Edmonton	Alberta
Canada	Zeidler Ledcor Centre - University of Alberta	Edmonton	Alberta
Canada	Maisonneuve-Rosemont Hospital	Montreal	Quebec
Germany	Agaplesion Markus Krankenhaus	Frankfurt am Main
Germany	Universitaetsklinikum Halle	Halle
Germany	Medizinische Hochschule Hannover	Hannover
Hungary	Szent Janos Korhaz es Eszak-budai Egyesitett Korhazak/I. Belgyogyaszat es Gastroenterologia	Budapest
Hungary	Pandy Kalman Megyei Korhaz, III. sz. Belosztaly-Gasztroenterologia	Gyula
Hungary	Karolina Korhaz Rendelointezet, Belgyogyaszat	Mosonmagyarovar
Hungary	Tolna Megyei Balassa Janos Korhaz / II. Belgyogyaszat	Szekszard
Italy	Azienda Ospedaliera Luigi Sacco	Milano
Italy	Azienda Ospedaliera di Padova	Padova
Italy	Policlinico Universitario Agostino Gemelli	Roma
Slovakia	Gastroenterologicke a hepatologicke oddelenie, V. interna klinika LFUK a UN Bratislava, Ruzinov	Bratislava
Slovakia	Gastroenterologicka ambulancia, GEA s.r.o.	Trnava
Sweden	Sahlgrenska Universitetssjukhuset Medicinkliniken	Goteborg
Sweden	Karolinska Universitetssjukhuset, GastroCentrum Medicin	Stockholm
Sweden	Akademiska sjukhuset, Mag tarmmottagningen	Uppsala
United States	Charlotte Gastroenterology and Hepatology, PLLC	Charlotte	North Carolina
United States	Clinical Research Institute of Michigan, LLC	Chesterfield	Michigan
United States	Metropolitan Gastroenterology Group, PC - Chevy Chase Clinical Research	Chevy Chase	Maryland
United States	University of Chicago Medical Center	Chicago	Illinois
United States	Clinical Research of West Florida, Inc.	Clearwater	Florida
United States	Gastroenterology Consultants of Clearwater	Clearwater	Florida
United States	West Coast Endoscopy Center	Clearwater	Florida
United States	Surgery Center of Columbia	Columbia	Missouri
United States	Gastro One	Germantown	Tennessee
United States	Borland-Groover Clinic	Jacksonville	Florida
United States	Jacksonville Center for Endoscopy	Jacksonville	Florida
United States	Clinical Research of the Rockies	Lafayette	Colorado
United States	Rocky Mountain Gastroenterology Associates, LLC	Lakewood	Colorado
United States	Arapahoe Gastroenterology, PC	Littleton	Colorado
United States	University of Louisville Healthcare Outpatient Center	Louisville	Kentucky
United States	University of Louisville Hospital	Louisville	Kentucky
United States	Center for Digestive and Liver Diseases, Inc.	Mexico	Missouri
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Asher Kornbluth, MD PC	New York	New York
United States	Mount Sinai School of Medicine	New York	New York
United States	Present, Chapman, Steinlauf and Marion	New York	New York
United States	Digestive and Liver Disease Specialists	Norfolk	Virginia
United States	Sentara Leigh Hospital	Norfolk	Virginia
United States	Sentara Norfolk General Hospital	Norfolk	Virginia
United States	Wake Internal Medicine Consultants, Inc.	Raleigh	North Carolina
United States	Wake Research Associates	Raleigh	North Carolina
United States	McGuire DVAMC	Richmond	Virginia
United States	University of California San Francisco	San Francisco	California
United States	USCF Endoscopy Unit at Mount Zion	San Francisco	California
United States	University of Washington Medical Center	Seattle	Washington
United States	Miami Research Associates	South Miami	Florida
United States	Cotton-O'Neil Clinical Research Center, Digestive Health	Topeka	Kansas
United States	Endoscopic Microsurgery Associates, PA	Towson	Maryland
United States	Center for Digestive Health	Troy	Michigan
United States	Utica Surgery Center	Utica	Michigan
United States	Metropolitan Gastroenterology Group, PC	Washington	District of Columbia
United States	Wake Forest University University Baptist Medical Center - Internal Medicine	Winston Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Pfizer	Athersys, Inc

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  Germany,  Hungary,  Italy,  Slovakia,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	Yes
Primary	Number of Participants With Treatment-Emergent AEs by System Organ Class (SOC)		Baseline up to Week 52	Yes
Primary	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	Yes
Secondary	Change From Baseline in Rectal Bleeding Mayo Subscore at Week 12 and Week 16	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, Week 12, Week 16	No
Secondary	Number of Participants With Laboratory Test Abnormalities	The total number of participants with laboratory test abnormalities with or without regard to baseline abnormality was assessed. Laboratory parameters included: hematology (hemoglobin, hematocrit, red blood cell [RBC] count, platelet count, white blood cell [WBC] count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes, erythrocyte sedimentation rate); chemistry (blood urea nitrogen and creatinine, glucose, calcium, sodium, potassium, chloride, total bicarbonate, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, uric acid, albumin, total protein; urinalysis (pH, glucose, protein, blood, ketones, nitrites, leukocyte esterase, microscopy (only if urine dipstick was positive for blood, protein, nitrites or leukocyte esterase); other (follicle-stimulating hormone, human chorionic gonadotropin, stool microbiology, creatinine kinase, direct bilirubin, indirect bilirubin, gamma-glutamyl transferase, international normalized ratio.	Baseline up to Week 24	Yes
Secondary	Number of Participants With Potentially Clinically Significant Vital Signs Findings	Vital signs assessment included pulse rate, systolic blood pressure (SBP) and diastolic blood pressure (DBP). Criteria for vital sign values meeting potential clinical concern included: SBP <90 millimeters of mercury (mm Hg) and >=30 mm Hg increase/decrease from baseline, DBP <50 mm Hg and >=20 mm Hg increase/decrease from baseline, pulse rate <40 or >120 beats per minute (bpm),	Baseline up to Week 52	Yes
Secondary	Fold Change From Baseline in Fecal Calprotectin at Weeks 4, 8, 12, and 16	Fecal calprotectin, a very stable marker, is a 36kDa calcium and zinc binding protein which is neutrophil-derived. It represents 60% of cytosolic proteins in granulocytes and is a measurement of neutrophil migration to the gastrointestinal tract.	Baseline, Weeks 4, 8, 12 and 16	No
Secondary	Fold Change From Baseline in C-Reactive Protein (CRP) at Weeks 4, 8, 12, and 16	CRP is an acute-phase protein which provides an objective criterion of inflammatory activity. CRP has a short half-life (19 hours) and therefore rises early after the onset of inflammation and rapidly decreases after resolution of the inflammation. It is induced by interleukin-6, TNF-alpha and other pro-inflammatory cytokines that are produced within the intestinal lamina propria.	Baseline, Weeks 4, 8, 12 and 16	No
Secondary	Percentage of Participants With Rectal Bleeding Mayo Subscore of Zero at Weeks 4, 8, 12, and 16	Mayo subscores for rectal bleeding range from 0 to 3 (0=no blood seen; 1=streaks of blood with stool less than half the time; 2=obvious blood with stool most of the time; 3=blood alone passes).	Week 4, 8, 12 and 16	No
Secondary	Percentage of Participants in Endoscopic Remission 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). Endoscopic remission is defined as modified Baron Endoscopic Score equal to 0.	Week 8	No
Secondary	Percentage of Participants in Clinical Remission at Week 8	Clinical remission is defined as a total Mayo score of 2 points or lower, with no individual subscores exceeding 1 point.	Week 8	No
Secondary	Percentage of Participants With Decrease From Baseline of at Least 1 Point in Rectal Bleeding Mayo Subscore at Weeks 4, 8, 12, and 16	Mayo subscores for rectal bleeding range from 0 to 3 (0=no blood seen; 1=streaks of blood with stool less than half the time; 2=obvious blood with stool most of the time; 3=blood alone passes). A decrease from baseline score indicates improvement.	Baseline, Weeks 4, 8, 12 and 16	No
Secondary	Percentage of Participants With Endoscopic Response at Week 8	Endoscopic response is defined as a decrease in modified Baron endoscopic score from baseline of at least 2 points.	Week 8	No
Secondary	Percentage of Participants in Clinical Response at Week 8	Clinical response is defined as a decrease in total Mayo score from baseline of at least 3 points and at least 30 percent (%), with an accompanying decrease in the subscore for rectal bleeding of at least 1 point or an absolute subscore for rectal bleeding of 0 or 1.	Week 8	No
Secondary	Change From Baseline in Total Mayo Scores at Week 8	Mayo Score is an instrument designed to measure disease activity of ulcerative colitis, with total score ranging from 0 to 12. It consists of 4 subscores (stool frequency, rectal bleeding, findings of flexible proctosigmoidoscopy, and physician global assessment [PGA]), each graded from 0 to 3, with higher scores indicating more severe disease.	Baseline, Week 8	No
Secondary	Change From Baseline in Partial Mayo Scores at Weeks 4, 8, 12, and 16	Mayo Score is an instrument designed to measure disease activity of ulcerative colitis. Mayo Score ranges from 0 to 12 points. It consists of 4 subscores, each graded from 0 to 3 with higher scores indicating more severe disease. A Partial Mayo Score (Mayo score without endoscopy) ranges from 0 (normal or inactive disease) to 9 (severe disease) and calculated as the sum of 3 subscores (stool frequency, rectal bleeding and PGA) with each ranging from 0 to 3 (0=normal, 1=mild, 2=moderate, 3=severe). Higher scores indicate more severe disease.	Baseline, Weeks 4, 8, 12 and 16	No
Secondary	Change From Baseline in Biopsy Histology Scores at Week 8	A 15 to 25 centimeter (cm) biopsy sample of inflamed mucosal tissue was taken from the worst affected area and scored using the Riley Index. The Riley Index is a histologic scoring system for the assessment of the activity and severity of ulcerative colitis, ranging from 0 to 24. It consists of 6 histologic features (acute inflammatory cell infiltrate, crypt abscesses, mucin depletion, surface epithelial integrity, chronic inflammatory cell infiltrate, and crypt architectural irregularities), all scored on a 4-point scale (higher scores indicate more severe disease).	Baseline and Week 8	No
Secondary	Change From Baseline in Patient-Reported Rectal Bleeding up to Week 16	Patient-reported diary data assessed the number of bowel movements (BM) per day when not having a flare and the presence of blood in the stools (rectal bleeding [RB]), if any.	Baseline and Week 16	No

External Links

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