Clinical Trial Results:
A Phase 2, Randomized, DoubleBlind, PlaceboControlled, Parallel Group, MultiCenter Study to Investigate the Safety and Efficacy of MultiStem (PF05285401) in Subjects With Moderate to Severe Ulcerative Colitis
Due to the EudraCT – Results system being out of service between 31 July 2015 and 12 January 2016, these results have been published in compliance with revised timelines.
Summary


EudraCT number 
201002276627 
Trial protocol 
SE BE HU SK IT 
Global end of trial date 
19 Nov 2014

Results information


Results version number 
v1(current) 
This version publication date 
27 Jul 2016

First version publication date 
27 Jul 2016

Other versions 
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information


Trial identification


Sponsor protocol code 
B3041001


Additional study identifiers


ISRCTN number 
  
US NCT number 
  
WHO universal trial number (UTN) 
  
Sponsors


Sponsor organisation name 
Pfizer, Inc.


Sponsor organisation address 
235 E 42nd Street, New York, United States, 10017


Public contact 
Pfizer, Inc., Pfizer ClinicalTrials.gov Call Center, 001 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com


Scientific contact 
Pfizer ClinicalTrials.gov Call Center, Pfizer, Inc., 001 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com


Paediatric regulatory details


Is trial part of an agreed paediatric investigation plan (PIP) 
No


Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? 
No


Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? 
No


Results analysis stage


Analysis stage 
Final


Date of interim/final analysis 
08 Jul 2015


Is this the analysis of the primary completion data? 
Yes


Primary completion date 
19 Nov 2014


Global end of trial reached? 
Yes


Global end of trial date 
19 Nov 2014


Was the trial ended prematurely? 
No


General information about the trial


Main objective of the trial 
The main objective of the trial was to evaluate the safety and tolerability of intravenous doses of MultiStem in moderatetosevere ulcerative colitis.


Protection of trial subjects 
The study used an independent External Data Monitoring Committee (EDMC), who was responsible for ongoing monitoring of the safety of subjects according to the Charter. The recommendations made by the EDMC to alter the conduct of the study was forwarded to Pfizer for final decision.


Background therapy 
  
Evidence for comparator 
  
Actual start date of recruitment 
28 Feb 2011


Long term followup planned 
No


Independent data monitoring committee (IDMC) involvement? 
Yes


Population of trial subjects


Number of subjects enrolled per country 

Country: Number of subjects enrolled 
Slovakia: 5


Country: Number of subjects enrolled 
Sweden: 9


Country: Number of subjects enrolled 
United States: 63


Country: Number of subjects enrolled 
Canada: 4


Country: Number of subjects enrolled 
Germany: 12


Country: Number of subjects enrolled 
Hungary: 10


Country: Number of subjects enrolled 
Italy: 2


Worldwide total number of subjects 
105


EEA total number of subjects 
38


Number of subjects enrolled per age group 

In utero 
0


Preterm newborn  gestational age < 37 wk 
0


Newborns (027 days) 
0


Infants and toddlers (28 days23 months) 
0


Children (211 years) 
0


Adolescents (1217 years) 
0


Adults (1864 years) 
95


From 65 to 84 years 
10


85 years and over 
0



Recruitment


Recruitment details 
  
Preassignment


Screening details 
There were 3 cohorts planned. Cohorts 1 and 2 each included 9 subjects. The size of Cohort 3 was reviewed as the study progressed, based purely upon emerging variability estimates of the primary endpoints.  
Period 1


Period 1 title 
Overall Study


Is this the baseline period? 
Yes  
Allocation method 
Randomised  controlled


Blinding used 
Double blind  
Roles blinded 
Investigator, Subject  
Arms


Are arms mutually exclusive 
Yes


Arm title

Cohort 1: Placebo, MultiStem 300  
Arm description 
Subjects received a single dose (Day 1) or 3 doses (Day 1, Week 1, Week 2) of placebo infusion, followed by a single dose of MultiStem 300 Million Cells infusion at Week 8.  
Arm type 
Experimental  
Investigational medicinal product name 
MultiStem


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Infusion


Routes of administration 
Intravenous use


Dosage and administration details 
300


Arm title

Cohort 2: Placebo, MultiStem 750  
Arm description 
Subjects received a single dose of placebo infusion on Day 1, followed by a single dose of MultiStem 750 Million Cells infusion at Week 8.  
Arm type 
Experimental  
Investigational medicinal product name 
MultiStem


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Infusion


Routes of administration 
Intravenous use


Dosage and administration details 
750


Arm title

Cohort 1: MultiStem 300, Placebo  
Arm description 
Subjects received a single dose of MultiStem 300 Million Cells infusion on Day 1, followed by a single dose of placebo infusion at Week 8.  
Arm type 
Experimental  
Investigational medicinal product name 
MultiStem


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Infusion


Routes of administration 
Intravenous use


Dosage and administration details 
300


Arm title

Cohort 1: MultiStem 300 (x3), Placebo  
Arm description 
Subjects received up to 3 doses of MultiStem 300 Million Cells infusion (Day 1, Week, Week 2), followed by a single dose of placebo infusion at Week 8.  
Arm type 
Experimental  
Investigational medicinal product name 
MultiStem


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Infusion


Routes of administration 
Intravenous use


Dosage and administration details 
300


Arm title

Cohort 2: MultiStem 750, Placebo  
Arm description 
Subjects received a single dose of MultiStem 750 Million Cells infusion on Day 1, followed by a single dose of placebo infusion at Week 8.  
Arm type 
Experimental  
Investigational medicinal product name 
MultiStem


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Infusion


Routes of administration 
Intravenous use


Dosage and administration details 
750


Arm title

Cohort 3: MultiStem 750, MultiStem 750  
Arm description 
Subjects received a single dose of MultiStem 750 Million Cells infusion on Day 1, followed by a single dose of MultiStem 750 Million Cells infusion at Week 8.  
Arm type 
Experimental  
Investigational medicinal product name 
MultiStem


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Infusion


Routes of administration 
Intravenous use


Dosage and administration details 
750


Arm title

Cohort 3: MultiStem 750, Placebo  
Arm description 
Subjects received a single dose of MultiStem 750 Million Cells infusion on Day 1, followed by a single dose of placebo infusion at Week 8.  
Arm type 
Experimental  
Investigational medicinal product name 
MultiStem


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Infusion


Routes of administration 
Intravenous use


Dosage and administration details 
750


Arm title

Cohort 3: Placebo, MultiStem 750  
Arm description 
Subjects received a single dose of placebo infusion on Day 1, followed by a single dose of MultiStem 750 Million Cells infusion at Week 8.  
Arm type 
Experimental  
Investigational medicinal product name 
MultiStem


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Infusion


Routes of administration 
Intravenous use


Dosage and administration details 
750


Arm title

Cohort 3: Placebo, Placebo  
Arm description 
Subjects received a single dose of placebo infusion on Day 1, followed by a single dose of placebo infusion at Week 8.  
Arm type 
Placebo  
Investigational medicinal product name 
Placebo


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Infusion


Routes of administration 
Intravenous use


Dosage and administration details 
placebo




Period 2


Period 2 title 
Pooled Cohort 3


Is this the baseline period? 
No  
Allocation method 
Randomised  controlled


Blinding used 
Double blind  
Roles blinded 
Subject, Investigator  
Arms


Are arms mutually exclusive 
No


Arm title

Pooled MultiStem  
Arm description 
  
Arm type 
Experimental  
Investigational medicinal product name 
MultiStem


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Infusion


Routes of administration 
Intravenous use


Dosage and administration details 
350 M or 750 M


Arm title

Pooled Placebo  
Arm description 
  
Arm type 
Placebo  
Investigational medicinal product name 
Placebo


Investigational medicinal product code 

Other name 

Pharmaceutical forms 
Infusion


Routes of administration 
Intravenous use


Dosage and administration details 
placebo





Baseline characteristics reporting groups


Reporting group title 
Cohort 1: Placebo, MultiStem 300


Reporting group description 
Subjects received a single dose (Day 1) or 3 doses (Day 1, Week 1, Week 2) of placebo infusion, followed by a single dose of MultiStem 300 Million Cells infusion at Week 8.  
Reporting group title 
Cohort 2: Placebo, MultiStem 750


Reporting group description 
Subjects received a single dose of placebo infusion on Day 1, followed by a single dose of MultiStem 750 Million Cells infusion at Week 8.  
Reporting group title 
Cohort 1: MultiStem 300, Placebo


Reporting group description 
Subjects received a single dose of MultiStem 300 Million Cells infusion on Day 1, followed by a single dose of placebo infusion at Week 8.  
Reporting group title 
Cohort 1: MultiStem 300 (x3), Placebo


Reporting group description 
Subjects received up to 3 doses of MultiStem 300 Million Cells infusion (Day 1, Week, Week 2), followed by a single dose of placebo infusion at Week 8.  
Reporting group title 
Cohort 2: MultiStem 750, Placebo


Reporting group description 
Subjects received a single dose of MultiStem 750 Million Cells infusion on Day 1, followed by a single dose of placebo infusion at Week 8.  
Reporting group title 
Cohort 3: MultiStem 750, MultiStem 750


Reporting group description 
Subjects received a single dose of MultiStem 750 Million Cells infusion on Day 1, followed by a single dose of MultiStem 750 Million Cells infusion at Week 8.  
Reporting group title 
Cohort 3: MultiStem 750, Placebo


Reporting group description 
Subjects received a single dose of MultiStem 750 Million Cells infusion on Day 1, followed by a single dose of placebo infusion at Week 8.  
Reporting group title 
Cohort 3: Placebo, MultiStem 750


Reporting group description 
Subjects received a single dose of placebo infusion on Day 1, followed by a single dose of MultiStem 750 Million Cells infusion at Week 8.  
Reporting group title 
Cohort 3: Placebo, Placebo


Reporting group description 
Subjects received a single dose of placebo infusion on Day 1, followed by a single dose of placebo infusion at Week 8.  



End points reporting groups


Reporting group title 
Cohort 1: Placebo, MultiStem 300


Reporting group description 
Subjects received a single dose (Day 1) or 3 doses (Day 1, Week 1, Week 2) of placebo infusion, followed by a single dose of MultiStem 300 Million Cells infusion at Week 8.  
Reporting group title 
Cohort 2: Placebo, MultiStem 750


Reporting group description 
Subjects received a single dose of placebo infusion on Day 1, followed by a single dose of MultiStem 750 Million Cells infusion at Week 8.  
Reporting group title 
Cohort 1: MultiStem 300, Placebo


Reporting group description 
Subjects received a single dose of MultiStem 300 Million Cells infusion on Day 1, followed by a single dose of placebo infusion at Week 8.  
Reporting group title 
Cohort 1: MultiStem 300 (x3), Placebo


Reporting group description 
Subjects received up to 3 doses of MultiStem 300 Million Cells infusion (Day 1, Week, Week 2), followed by a single dose of placebo infusion at Week 8.  
Reporting group title 
Cohort 2: MultiStem 750, Placebo


Reporting group description 
Subjects received a single dose of MultiStem 750 Million Cells infusion on Day 1, followed by a single dose of placebo infusion at Week 8.  
Reporting group title 
Cohort 3: MultiStem 750, MultiStem 750


Reporting group description 
Subjects received a single dose of MultiStem 750 Million Cells infusion on Day 1, followed by a single dose of MultiStem 750 Million Cells infusion at Week 8.  
Reporting group title 
Cohort 3: MultiStem 750, Placebo


Reporting group description 
Subjects received a single dose of MultiStem 750 Million Cells infusion on Day 1, followed by a single dose of placebo infusion at Week 8.  
Reporting group title 
Cohort 3: Placebo, MultiStem 750


Reporting group description 
Subjects received a single dose of placebo infusion on Day 1, followed by a single dose of MultiStem 750 Million Cells infusion at Week 8.  
Reporting group title 
Cohort 3: Placebo, Placebo


Reporting group description 
Subjects received a single dose of placebo infusion on Day 1, followed by a single dose of placebo infusion at Week 8.  
Reporting group title 
Pooled MultiStem


Reporting group description 
  
Reporting group title 
Pooled Placebo


Reporting group description 
 


End point title 
Change From Baseline in Endoscopic Score (as Measured by Modified Baron Score) at Week 8  
End point description 
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).


End point type 
Primary


End point timeframe 
Baseline and Week 8




Statistical analysis title 
Change From Baseline in Endoscopic Score (Week 8)  
Statistical analysis description 
Pooled MultiStem versus Pooled Placebo


Comparison groups 
Pooled MultiStem v Pooled Placebo


Number of subjects included in analysis 
88


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.96 ^{[1]}  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.4


Confidence interval 

level 
80%  
sides 
2sided


lower limit 
0.12  
upper limit 
0.69  
Variability estimate 
Standard error of the mean


Dispersion value 
0.223


Notes [1]  1sided pvalue 


End point title 
Change From Baseline in Rectal Bleeding Mayo Subscore at Week 4  
End point description 
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.


End point type 
Primary


End point timeframe 
Baseline and Week 4




Statistical analysis title 
Rectal Bleeding Mayo Subscore (Week 4)  
Statistical analysis description 
Pooled MultiStem versus Pooled Placebo (Week 4)


Comparison groups 
Pooled MultiStem v Pooled Placebo


Number of subjects included in analysis 
88


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.54 ^{[2]}  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.02


Confidence interval 

level 
80%  
sides 
2sided


lower limit 
0.19  
upper limit 
0.22  
Variability estimate 
Standard error of the mean


Dispersion value 
0.161


Notes [2]  1sided pvalue 


End point title 
Change From Baseline in Rectal Bleeding Mayo Subscore at Week 8  
End point description 
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.


End point type 
Primary


End point timeframe 
Baseline and Week 8




Statistical analysis title 
Rectal Bleeding Mayo Subscore (Week 8)  
Statistical analysis description 
Pooled MultiStem versus Pooled Placebo (Week 8)


Comparison groups 
Pooled MultiStem v Pooled Placebo


Number of subjects included in analysis 
88


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.67 ^{[3]}  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.08


Confidence interval 

level 
80%  
sides 
2sided


lower limit 
0.15  
upper limit 
0.3  
Variability estimate 
Standard error of the mean


Dispersion value 
0.174


Notes [3]  1sided pvalue 


End point title 
Number of Subjects with TreatmentEmergent Adverse Events (AEs) and Serious Adverse Events (SAEs) ^{[4]}  
End point description 
An AE was any untoward medical occurrence in a subject 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; lifethreatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatmentemergent 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 pretreatment state. AEs included both SAEs and nonSAEs.


End point type 
Primary


End point timeframe 
Baseline up to Week 52


Notes [4]  No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this primary endpoint. Adverse events were reported in accordance with the sponsor reporting standards. 



No statistical analyses for this end point 


End point title 
Incidence of TreatmentEmergent AEs by System Organ Class (SOC) ^{[5]}  
End point description 

End point type 
Primary


End point timeframe 
Baseline up to Week 52


Notes [5]  No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this primary endpoint. Adverse events were reported in accordance with the sponsor reporting standards. 



No statistical analyses for this end point 


End point title 
Number of TreatmentEmergent AEs by Severity ^{[6]}  
End point description 
The intensity grades were defined as follows: mild=does not interfere with subject's usual function; moderate=interferes to some extent with subject's usual function; severe=interferes significantly with subject's usual function.


End point type 
Primary


End point timeframe 
Baseline up to Week 52


Notes [6]  No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this primary endpoint. Adverse events were reported in accordance with the sponsor reporting standards. 



No statistical analyses for this end point 


End point title 
Change From Baseline in Rectal Bleeding Mayo Subscore at Week 12 and Week 16  
End point description 
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.


End point type 
Secondary


End point timeframe 
Baseline, Week 12, Week 16




No statistical analyses for this end point 


End point title 
Number of Subjects With Laboratory Test Abnormalities  
End point description 
The total number of subjects 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 (folliclestimulating hormone, human chorionic gonadotropin, stool microbiology, creatinine kinase, direct bilirubin, indirect bilirubin, gammaglutamyl transferase, international normalized ratio.


End point type 
Secondary


End point timeframe 
Baseline up to Week 24




No statistical analyses for this end point 


End point title 
Number of Subjects With Potentially Clinically Significant Vital Signs Findings  
End point description 
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),


End point type 
Secondary


End point timeframe 
Baseline up to Week 52




No statistical analyses for this end point 


End point title 
Fold Change From Baseline in Fecal Calprotectin at Weeks 4, 8, 12, and 16  
End point description 
Fecal calprotectin, a very stable marker, is a 36kDa calcium and zinc binding protein which is neutrophilderived. It represents 60% of cytosolic proteins in granulocytes and is a measurement of neutrophil migration to the gastrointestinal tract.


End point type 
Secondary


End point timeframe 
Baseline, Weeks 4, 8, 12 and 16




Statistical analysis title 
Fecal Calprotectin (Week 4)  
Statistical analysis description 
Pooled MultiStem versus Pooled Placebo (Week 4)


Comparison groups 
Cohort 3: MultiStem 750, MultiStem 750 v Cohort 3: MultiStem 750, Placebo v Cohort 3: Placebo, MultiStem 750 v Cohort 3: Placebo, Placebo


Number of subjects included in analysis 
88


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.53 ^{[7]}  
Method 
Mixed models analysis  
Parameter type 
Geometric Mean Ratio  
Point estimate 
1.02


Confidence interval 

level 
80%  
sides 
2sided


lower limit 
0.73  
upper limit 
1.42  
Notes [7]  1sided pvalue 

Statistical analysis title 
Fecal Calprotectin (Week 8)  
Statistical analysis description 
Pooled MultiStem versus Pooled Placebo (Week 8)


Comparison groups 
Cohort 3: MultiStem 750, MultiStem 750 v Cohort 3: MultiStem 750, Placebo v Cohort 3: Placebo, MultiStem 750 v Cohort 3: Placebo, Placebo


Number of subjects included in analysis 
88


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.91 ^{[8]}  
Method 
Mixed models analysis  
Parameter type 
Geometric Mean Ratio  
Point estimate 
1.48


Confidence interval 

level 
80%  
sides 
2sided


lower limit 
1.02  
upper limit 
2.14  
Notes [8]  1sided pvalue 

Statistical analysis title 
Fecal Calprotectin (Week 12)  
Statistical analysis description 
Cohort 3 MM versus Cohort 3 PP (Week 12)


Comparison groups 
Cohort 3: MultiStem 750, MultiStem 750 v Cohort 3: Placebo, Placebo


Number of subjects included in analysis 
44


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.81 ^{[9]}  
Method 
Mixed models analysis  
Parameter type 
Geometric Mean Ratio  
Point estimate 
1.38


Confidence interval 

level 
80%  
sides 
2sided


lower limit 
0.86  
upper limit 
2.23  
Notes [9]  1sided pvalue 

Statistical analysis title 
Fecal Calprotectin (Week 12)  
Statistical analysis description 
Cohort 3 MP versus Cohort 3 PP (Week 12)


Comparison groups 
Cohort 3: MultiStem 750, Placebo v Cohort 3: Placebo, Placebo


Number of subjects included in analysis 
46


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.44 ^{[10]}  
Method 
Mixed models analysis  
Parameter type 
Geometric Mean Ratio  
Point estimate 
0.94


Confidence interval 

level 
80%  
sides 
2sided


lower limit 
0.59  
upper limit 
1.51  
Notes [10]  1sided pvalue 

Statistical analysis title 
Fecal Calprotectin (Week 12)  
Statistical analysis description 
Cohort 3 PM versus Cohort 3 PP (Week 12)


Comparison groups 
Cohort 3: Placebo, MultiStem 750 v Cohort 3: Placebo, Placebo


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.67 ^{[11]}  
Method 
Mixed models analysis  
Parameter type 
Geometric Mean Ratio  
Point estimate 
1.18


Confidence interval 

level 
80%  
sides 
2sided


lower limit 
0.72  
upper limit 
1.94  
Notes [11]  1sided pvalue 

Statistical analysis title 
Fecal Calprotectin (Week 16)  
Statistical analysis description 
Cohort 3 MM versus Cohort 3 PP (Week 16)


Comparison groups 
Cohort 3: MultiStem 750, MultiStem 750 v Cohort 3: Placebo, Placebo


Number of subjects included in analysis 
44


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.62 ^{[12]}  
Method 
Mixed models analysis  
Parameter type 
Geometric Mean Ratio  
Point estimate 
1.12


Confidence interval 

level 
80%  
sides 
2sided


lower limit 
0.68  
upper limit 
1.84  
Notes [12]  1sided pvalue 

Statistical analysis title 
Fecal Calprotectin (Week 16)  
Statistical analysis description 
Cohort 3 MP versus Cohort 3 PP (Week 16)


Comparison groups 
Cohort 3: MultiStem 750, Placebo v Cohort 3: Placebo, Placebo


Number of subjects included in analysis 
46


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.45 ^{[13]}  
Method 
Mixed models analysis  
Parameter type 
Geometric Mean Ratio  
Point estimate 
0.95


Confidence interval 

level 
80%  
sides 
2sided


lower limit 
0.58  
upper limit 
1.57  
Notes [13]  1sided pvalue 

Statistical analysis title 
Fecal Calprotectin (Week 16)  
Statistical analysis description 
Cohort 3 PM versus Cohort 3 PP (Week 16)


Comparison groups 
Cohort 3: Placebo, MultiStem 750 v Cohort 3: Placebo, Placebo


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.3 ^{[14]}  
Method 
Mixed models analysis  
Parameter type 
Geometric Mean Ratio  
Point estimate 
0.81


Confidence interval 

level 
80%  
sides 
2sided


lower limit 
0.49  
upper limit 
1.36  
Notes [14]  1sided pvalue 


End point title 
Fold Change From Baseline in CReactive Protein (CRP) at Weeks 4, 8, 12, and 16  
End point description 
CRP is an acutephase protein which provides an objective criterion of inflammatory activity. CRP has a short halflife (19 hours) and therefore rises early after the onset of inflammation and rapidly decreases after resolution of the inflammation. It is induced by interleukin6, TNFalpha and other proinflammatory cytokines that are produced within the intestinal lamina propria.


End point type 
Secondary


End point timeframe 
Baseline, Weeks 4, 8, 12 and 16




Statistical analysis title 
Fold Change From Baseline in CRP (Week 4)  
Statistical analysis description 
Pooled MultiStem versus Pooled Placebo (Week 4)


Comparison groups 
Cohort 3: MultiStem 750, MultiStem 750 v Cohort 3: MultiStem 750, Placebo v Cohort 3: Placebo, MultiStem 750 v Cohort 3: Placebo, Placebo


Number of subjects included in analysis 
88


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.79 ^{[15]}  
Method 
Mixed models analysis  
Parameter type 
Geometric Mean Ratio  
Point estimate 
1.17


Confidence interval 

level 
80%  
sides 
2sided


lower limit 
0.91  
upper limit 
1.51  
Notes [15]  1sided pvalue 

Statistical analysis title 
Fold Change From Baseline in CRP (Week 8)  
Statistical analysis description 
Pooled MultiStem versus Pooled Placebo (Week 8)


Comparison groups 
Cohort 3: MultiStem 750, MultiStem 750 v Cohort 3: MultiStem 750, Placebo v Cohort 3: Placebo, MultiStem 750 v Cohort 3: Placebo, Placebo


Number of subjects included in analysis 
88


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.8 ^{[16]}  
Method 
Mixed models analysis  
Parameter type 
Geometric Mean Ratio  
Point estimate 
1.21


Confidence interval 

level 
80%  
sides 
2sided


lower limit 
0.9  
upper limit 
1.63  
Notes [16]  1sided pvalue 

Statistical analysis title 
Fold Change From Baseline in CRP (Week 12)  
Statistical analysis description 
Cohort 3 MM versus Cohort 3 PP (Week 12)


Comparison groups 
Cohort 3: MultiStem 750, MultiStem 750 v Cohort 3: Placebo, Placebo


Number of subjects included in analysis 
44


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.99 ^{[17]}  
Method 
Mixed models analysis  
Parameter type 
Geometric Mean Ratio  
Point estimate 
2.75


Confidence interval 

level 
80%  
sides 
2sided


lower limit 
1.63  
upper limit 
4.64  
Notes [17]  1sided pvalue 

Statistical analysis title 
Fold Change From Baseline in CRP (Week 12)  
Statistical analysis description 
Cohort 3 MP versus Cohort 3 PP (Week 12)


Comparison groups 
Cohort 3: MultiStem 750, Placebo v Cohort 3: Placebo, Placebo


Number of subjects included in analysis 
46


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.96 ^{[18]}  
Method 
Mixed models analysis  
Parameter type 
Geometric Mean Ratio  
Point estimate 
1.96


Confidence interval 

level 
80%  
sides 
2sided


lower limit 
1.19  
upper limit 
3.25  
Notes [18]  1sided pvalue 

Statistical analysis title 
Fold Change From Baseline in CRP (Week 12)  
Statistical analysis description 
Cohort 3 PM versus Cohort 3 PP (Week 12)


Comparison groups 
Cohort 3: Placebo, MultiStem 750 v Cohort 3: Placebo, Placebo


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.95 ^{[19]}  
Method 
Mixed models analysis  
Parameter type 
Geometric Mean Ratio  
Point estimate 
1.98


Confidence interval 

level 
80%  
sides 
2sided


lower limit 
1.15  
upper limit 
3.41  
Notes [19]  1sided pvalue 

Statistical analysis title 
Fold Change From Baseline in CRP (Week 16)  
Statistical analysis description 
Cohort 3 MM versus Cohort 3 PP (Week 16)


Comparison groups 
Cohort 3: MultiStem 750, MultiStem 750 v Cohort 3: Placebo, Placebo


Number of subjects included in analysis 
44


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.99 ^{[20]}  
Method 
Mixed models analysis  
Parameter type 
Geometric Mean Ratio  
Point estimate 
2.3


Confidence interval 

level 
80%  
sides 
2sided


lower limit 
1.52  
upper limit 
3.48  
Notes [20]  1sided pvalue 

Statistical analysis title 
Fold Change From Baseline in CRP (Week 16)  
Statistical analysis description 
Cohort 3 MP versus Cohort 3 PP (Week 16)


Comparison groups 
Cohort 3: MultiStem 750, Placebo v Cohort 3: Placebo, Placebo


Number of subjects included in analysis 
46


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.62 ^{[21]}  
Method 
Mixed models analysis  
Parameter type 
Geometric Mean Ratio  
Point estimate 
1.1


Confidence interval 

level 
80%  
sides 
2sided


lower limit 
0.74  
upper limit 
1.63  
Notes [21]  1sided pvalue 

Statistical analysis title 
Fold Change From Baseline in CRP (Week 16)  
Statistical analysis description 
Cohort 3 PM versus Cohort 3 PP (Week 16)


Comparison groups 
Cohort 3: Placebo, MultiStem 750 v Cohort 3: Placebo, Placebo


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.89 ^{[22]}  
Method 
Mixed models analysis  
Parameter type 
Geometric Mean Ratio  
Point estimate 
1.51


Confidence interval 

level 
80%  
sides 
2sided


lower limit 
0.98  
upper limit 
2.32  
Notes [22]  1sided pvalue 


End point title 
Percentage of Subjects With Rectal Bleeding Mayo Subscore of Zero at Weeks 4, 8, 12, and 16  
End point description 
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).


End point type 
Secondary


End point timeframe 
Week 4, 8, 12 and 16




Statistical analysis title 
Rectal Bleeding Mayo Subscore of Zero (Week 4)  
Statistical analysis description 
Pooled MultiStem versus Pooled Placebo (Week 4)


Comparison groups 
Cohort 3: MultiStem 750, MultiStem 750 v Cohort 3: MultiStem 750, Placebo v Cohort 3: Placebo, MultiStem 750 v Cohort 3: Placebo, Placebo


Number of subjects included in analysis 
88


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.34 ^{[23]}  
Method 
Regression, Logistic  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.21


Confidence interval 

level 
80%  
sides 
2sided


lower limit 
0.66  
upper limit 
2.19  
Notes [23]  1sided pvalue 

Statistical analysis title 
Rectal Bleeding Mayo Subscore of Zero (Week 8)  
Statistical analysis description 
Pooled MultiStem versus Pooled Placebo (Week 8)


Comparison groups 
Cohort 3: MultiStem 750, MultiStem 750 v Cohort 3: MultiStem 750, Placebo v Cohort 3: Placebo, MultiStem 750 v Cohort 3: Placebo, Placebo


Number of subjects included in analysis 
88


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.33 ^{[24]}  
Method 
Regression, Logistic  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.23


Confidence interval 

level 
80%  
sides 
2sided


lower limit 
0.68  
upper limit 
2.23  
Notes [24]  1sided pvalue 

Statistical analysis title 
Rectal Bleeding Mayo Subscore of Zero (Week 12)  
Statistical analysis description 
Cohort 3 MM versus Cohort 3 PP (Week 12)


Comparison groups 
Cohort 3: MultiStem 750, MultiStem 750 v Cohort 3: Placebo, Placebo


Number of subjects included in analysis 
44


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.1 ^{[25]}  
Method 
Regression, Logistic  
Parameter type 
Odds ratio (OR)  
Point estimate 
2.37


Confidence interval 

level 
80%  
sides 
2sided


lower limit 
0.99  
upper limit 
5.67  
Notes [25]  1sided pvalue 

Statistical analysis title 
Rectal Bleeding Mayo Subscore of Zero (Week 12)  
Statistical analysis description 
Cohort 3 MP versus Cohort 3 PP (Week 12)


Comparison groups 
Cohort 3: MultiStem 750, Placebo v Cohort 3: Placebo, Placebo


Number of subjects included in analysis 
46


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.74 ^{[26]}  
Method 
Regression, Logistic  
Parameter type 
Odds ratio (OR)  
Point estimate 
0.66


Confidence interval 

level 
80%  
sides 
2sided


lower limit 
0.28  
upper limit 
1.55  
Notes [26]  1sided pvalue 

Statistical analysis title 
Rectal Bleeding Mayo Subscore of Zero (Week 12)  
Statistical analysis description 
Cohort 3 PM versus Cohort 3 PP (Week 12)


Comparison groups 
Cohort 3: Placebo, MultiStem 750 v Cohort 3: Placebo, Placebo


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.48 ^{[27]}  
Method 
Regression, Logistic  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.04


Confidence interval 

level 
80%  
sides 
2sided


lower limit 
0.41  
upper limit 
2.64  
Notes [27]  1sided pvalue 

Statistical analysis title 
Rectal Bleeding Mayo Subscore of Zero (Week 16)  
Statistical analysis description 
Cohort 3 MM versus Cohort 3 PP (Week 16)


Comparison groups 
Cohort 3: MultiStem 750, MultiStem 750 v Cohort 3: Placebo, Placebo


Number of subjects included in analysis 
44


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.58 ^{[28]}  
Method 
Regression, Logistic  
Parameter type 
Odds ratio (OR)  
Point estimate 
0.88


Confidence interval 

level 
80%  
sides 
2sided


lower limit 
0.38  
upper limit 
2.03  
Notes [28]  1sided pvalue 

Statistical analysis title 
Rectal Bleeding Mayo Subscore of Zero (Week 16)  
Statistical analysis description 
Cohort 3 MP versus Cohort 3 PP (Week 16)


Comparison groups 
Cohort 3: MultiStem 750, Placebo v Cohort 3: Placebo, Placebo


Number of subjects included in analysis 
46


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.68 ^{[29]}  
Method 
Regression, Logistic  
Parameter type 
Odds ratio (OR)  
Point estimate 
0.74


Confidence interval 

level 
80%  
sides 
2sided


lower limit 
0.33  
upper limit 
1.66  
Notes [29]  1sided pvalue 

Statistical analysis title 
Rectal Bleeding Mayo Subscore of Zero (Week 16)  
Statistical analysis description 
Cohort 3 PM versus Cohort 3 PP (Week 16)


Comparison groups 
Cohort 3: Placebo, MultiStem 750 v Cohort 3: Placebo, Placebo


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.84 ^{[30]}  
Method 
Regression, Logistic  
Parameter type 
Odds ratio (OR)  
Point estimate 
0.51


Confidence interval 

level 
80%  
sides 
2sided


lower limit 
0.21  
upper limit 
1.23  
Notes [30]  1sided pvalue 


End point title 
Percentage of Subjects in Endoscopic Remission at Week 8  
End point description 
Endoscopic remission is defined as modified Baron Endoscopic Score equal to 0.


End point type 
Secondary


End point timeframe 
Week 8




Statistical analysis title 
Endoscopic Remission (Week 8)  
Statistical analysis description 
Pooled MultiStem versus Pooled Placebo


Comparison groups 
Cohort 3: MultiStem 750, MultiStem 750 v Cohort 3: MultiStem 750, Placebo v Cohort 3: Placebo, MultiStem 750 v Cohort 3: Placebo, Placebo


Number of subjects included in analysis 
88


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.57 ^{[31]}  
Method 
Regression, Logistic  
Parameter type 
Odds ratio (OR)  
Point estimate 
0.83


Confidence interval 

level 
80%  
sides 
2sided


lower limit 
0.22  
upper limit 
3.07  
Notes [31]  1sided pvalue 


End point title 
Percentage of Subjects in Clinical Remission at Week 8  
End point description 
Clinical remission is defined as a total Mayo score of 2 points or lower, with no individual subscores exceeding 1 point.


End point type 
Secondary


End point timeframe 
Week 8




Statistical analysis title 
Clinical Remission (Week 8)  
Statistical analysis description 
Pooled MultiStem versus Pooled Placebo


Comparison groups 
Cohort 3: MultiStem 750, MultiStem 750 v Cohort 3: MultiStem 750, Placebo v Cohort 3: Placebo, MultiStem 750 v Cohort 3: Placebo, Placebo


Number of subjects included in analysis 
88


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.85 ^{[32]}  
Method 
Regression, Logistic  
Parameter type 
Odds ratio (OR)  
Point estimate 
0.39


Confidence interval 

level 
80%  
sides 
2sided


lower limit 
0.12  
upper limit 
1.23  
Notes [32]  1sided pvalue 


End point title 
Percentage of Subjects With Decrease From Baseline of at Least 1 Point in Rectal Bleeding Mayo Subscore at Weeks 4, 8, 12, and 16  
End point description 
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.


End point type 
Secondary


End point timeframe 
Baseline, Weeks 4, 8, 12 and 16




Statistical analysis title 
Rectal Bleeding Mayo Subscore (Week 4)  
Statistical analysis description 
Pooled MultiStem versus Pooled Placebo (Week 4)


Comparison groups 
Cohort 3: MultiStem 750, MultiStem 750 v Cohort 3: MultiStem 750, Placebo v Cohort 3: Placebo, MultiStem 750 v Cohort 3: Placebo, Placebo


Number of subjects included in analysis 
88


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.05 ^{[33]}  
Method 
Regression, Logistic  
Parameter type 
Odds ratio (OR)  
Point estimate 
2.27


Confidence interval 

level 
80%  
sides 
2sided


lower limit 
1.21  
upper limit 
4.24  
Notes [33]  1sided pvalue 

Statistical analysis title 
Rectal Bleeding Mayo Subscore (Week 8)  
Statistical analysis description 
Pooled MultiStem versus Pooled Placebo (Week 8)


Comparison groups 
Cohort 3: MultiStem 750, MultiStem 750 v Cohort 3: MultiStem 750, Placebo v Cohort 3: Placebo, MultiStem 750 v Cohort 3: Placebo, Placebo


Number of subjects included in analysis 
88


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.43 ^{[34]}  
Method 
Regression, Logistic  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.09


Confidence interval 

level 
80%  
sides 
2sided


lower limit 
0.61  
upper limit 
1.95  
Notes [34]  1sided pvalue 

Statistical analysis title 
Rectal Bleeding Mayo Subscore (Week 12)  
Statistical analysis description 
Cohort 3 MM versus Cohort 3 PP (Week 12)


Comparison groups 
Cohort 3: MultiStem 750, MultiStem 750 v Cohort 3: Placebo, Placebo


Number of subjects included in analysis 
44


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.44 ^{[35]}  
Method 
Regression, Logistic  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.11


Confidence interval 

level 
80%  
sides 
2sided


lower limit 
0.45  
upper limit 
2.76  
Notes [35]  1sided pvalue 

Statistical analysis title 
Rectal Bleeding Mayo Subscore (Week 12)  
Statistical analysis description 
Cohort 3 MP versus Cohort 3 PP (Week 12)


Comparison groups 
Cohort 3: MultiStem 750, Placebo v Cohort 3: Placebo, Placebo


Number of subjects included in analysis 
46


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.38 ^{[36]}  
Method 
Regression, Logistic  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.23


Confidence interval 

level 
80%  
sides 
2sided


lower limit 
0.5  
upper limit 
3.04  
Notes [36]  1sided pvalue 

Statistical analysis title 
Rectal Bleeding Mayo Subscore (Week 12)  
Statistical analysis description 
Cohort 3 PM versus Cohort 3 PP (Week 12)


Comparison groups 
Cohort 3: Placebo, MultiStem 750 v Cohort 3: Placebo, Placebo


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.89 ^{[37]}  
Method 
Regression, Logistic  
Parameter type 
Odds ratio (OR)  
Point estimate 
0.38


Confidence interval 

level 
80%  
sides 
2sided


lower limit 
0.14  
upper limit 
1.04  
Notes [37]  1sided pvalue 

Statistical analysis title 
Rectal Bleeding Mayo Subscore (Week 16)  
Statistical analysis description 
Cohort 3 MM versus Cohort 3 PP (Week 16)


Comparison groups 
Cohort 3: MultiStem 750, MultiStem 750 v Cohort 3: Placebo, Placebo


Number of subjects included in analysis 
44


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.47 ^{[38]}  
Method 
Regression, Logistic  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.05


Confidence interval 

level 
80%  
sides 
2sided


lower limit 
0.45  
upper limit 
2.42  
Notes [38]  1sided pvalue 

Statistical analysis title 
Rectal Bleeding Mayo Subscore (Week 16)  
Statistical analysis description 
Cohort 3 MP versus Cohort 3 PP (Week 16)


Comparison groups 
Cohort 3: MultiStem 750, Placebo v Cohort 3: Placebo, Placebo


Number of subjects included in analysis 
46


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.24 ^{[39]}  
Method 
Regression, Logistic  
Parameter type 
Odds ratio (OR)  
Point estimate 
1.58


Confidence interval 

level 
80%  
sides 
2sided


lower limit 
0.7  
upper limit 
3.57  
Notes [39]  1sided pvalue 

Statistical analysis title 
Rectal Bleeding Mayo Subscore (Week 16)  
Statistical analysis description 
Cohort 3 PM versus Cohort 3 PP (Week 16)


Comparison groups 
Cohort 3: Placebo, MultiStem 750 v Cohort 3: Placebo, Placebo


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.81 ^{[40]}  
Method 
Regression, Logistic  
Parameter type 
Odds ratio (OR)  
Point estimate 
0.53


Confidence interval 

level 
80%  
sides 
2sided


lower limit 
0.22  
upper limit 
1.32  
Notes [40]  1sided pvalue 


End point title 
Percentage of Subjects With Endoscopic Response at Week 8  
End point description 
Endoscopic response is defined as a decrease in modified Baron endoscopic score from baseline of at least 2 points.


End point type 
Secondary


End point timeframe 
Week 8




Statistical analysis title 
Endoscopic Response (Week 8)  
Statistical analysis description 
Pooled MultiStem versus Pooled Placebo


Comparison groups 
Cohort 3: MultiStem 750, MultiStem 750 v Cohort 3: MultiStem 750, Placebo v Cohort 3: Placebo, MultiStem 750 v Cohort 3: Placebo, Placebo


Number of subjects included in analysis 
88


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.84 ^{[41]}  
Method 
Regression, Logistic  
Parameter type 
Odds ratio (OR)  
Point estimate 
0.49


Confidence interval 

level 
80%  
sides 
2sided


lower limit 
0.2  
upper limit 
1.24  
Notes [41]  1sided pvalue 


End point title 
Percentage of Subjects in Clinical Response at Week 8  
End point description 
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.


End point type 
Secondary


End point timeframe 
Week 8




Statistical analysis title 
Clinical Response (Week 8)  
Statistical analysis description 
Pooled MultiStem versus Pooled Placebo


Comparison groups 
Cohort 3: MultiStem 750, MultiStem 750 v Cohort 3: MultiStem 750, Placebo v Cohort 3: Placebo, MultiStem 750 v Cohort 3: Placebo, Placebo


Number of subjects included in analysis 
88


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.96 ^{[42]}  
Method 
Regression, Logistic  
Parameter type 
Odds ratio (OR)  
Point estimate 
0.3


Confidence interval 

level 
80%  
sides 
2sided


lower limit 
0.12  
upper limit 
0.73  
Notes [42]  1sided pvalue 


End point title 
Change From Baseline in Total Mayo Scores at Week 8  
End point description 
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.


End point type 
Secondary


End point timeframe 
Baseline, Week 8




Statistical analysis title 
Total Mayo Scores (Week 8)  
Statistical analysis description 
Pooled MultiStem versus Pooled Placebo


Comparison groups 
Cohort 3: MultiStem 750, MultiStem 750 v Cohort 3: MultiStem 750, Placebo v Cohort 3: Placebo, MultiStem 750 v Cohort 3: Placebo, Placebo


Number of subjects included in analysis 
88


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.87 ^{[43]}  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.58


Confidence interval 

level 
80%  
sides 
2sided


lower limit 
0.08  
upper limit 
1.24  
Variability estimate 
Standard error of the mean


Dispersion value 
0.513


Notes [43]  1sided pvalue 


End point title 
Change From Baseline in Partial Mayo Scores at Weeks 4, 8, 12, and 16  
End point description 
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.


End point type 
Secondary


End point timeframe 
Baseline, Weeks 4, 8, 12 and 16




Statistical analysis title 
Partial Mayo Scores (Week 4)  
Statistical analysis description 
Pooled MultiStem versus Pooled Placebo (Week 4)


Comparison groups 
Cohort 3: MultiStem 750, MultiStem 750 v Cohort 3: MultiStem 750, Placebo v Cohort 3: Placebo, MultiStem 750 v Cohort 3: Placebo, Placebo


Number of subjects included in analysis 
88


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.8 ^{[44]}  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.29


Confidence interval 

level 
80%  
sides 
2sided


lower limit 
0.15  
upper limit 
0.74  
Variability estimate 
Standard error of the mean


Dispersion value 
0.345


Notes [44]  1sided pvalue 

Statistical analysis title 
Partial Mayo Scores (Week 8)  
Statistical analysis description 
Pooled MultiStem versus Pooled Placebo (Week 8)


Comparison groups 
Cohort 3: MultiStem 750, MultiStem 750 v Cohort 3: MultiStem 750, Placebo v Cohort 3: Placebo, MultiStem 750 v Cohort 3: Placebo, Placebo


Number of subjects included in analysis 
88


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.77 ^{[45]}  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.3


Confidence interval 

level 
80%  
sides 
2sided


lower limit 
0.23  
upper limit 
0.84  
Variability estimate 
Standard error of the mean


Dispersion value 
0.418


Notes [45]  1sided pvalue 

Statistical analysis title 
Partial Mayo Scores (Week 12)  
Statistical analysis description 
Cohort 3 MM versus Cohort 3 PP (Week 12)


Comparison groups 
Cohort 3: MultiStem 750, MultiStem 750 v Cohort 3: Placebo, Placebo


Number of subjects included in analysis 
44


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.74 ^{[46]}  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.44


Confidence interval 

level 
80%  
sides 
2sided


lower limit 
0.42  
upper limit 
1.3  
Variability estimate 
Standard error of the mean


Dispersion value 
0.666


Notes [46]  1sided pvalue 

Statistical analysis title 
Partial Mayo Scores (Week 12)  
Statistical analysis description 
Cohort 3 MP versus Cohort 3 PP (Week 12)


Comparison groups 
Cohort 3: MultiStem 750, Placebo v Cohort 3: Placebo, Placebo


Number of subjects included in analysis 
46


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.88 ^{[47]}  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.76


Confidence interval 

level 
80%  
sides 
2sided


lower limit 
0.08  
upper limit 
1.59  
Variability estimate 
Standard error of the mean


Dispersion value 
0.645


Notes [47]  1sided pvalue 

Statistical analysis title 
Partial Mayo Scores (Week 12)  
Statistical analysis description 
Cohort 3 PM versus Cohort 3 PP (Week 12)


Comparison groups 
Cohort 3: Placebo, MultiStem 750 v Cohort 3: Placebo, Placebo


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.72 ^{[48]}  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.42


Confidence interval 

level 
80%  
sides 
2sided


lower limit 
0.5  
upper limit 
1.33  
Variability estimate 
Standard error of the mean


Dispersion value 
0.705


Notes [48]  1sided pvalue 

Statistical analysis title 
Partial Mayo Scores (Week 16)  
Statistical analysis description 
Cohort 3 MM versus Cohort 3 PP (Week 16)


Comparison groups 
Cohort 3: MultiStem 750, MultiStem 750 v Cohort 3: Placebo, Placebo


Number of subjects included in analysis 
44


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.97 ^{[49]}  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
1.21


Confidence interval 

level 
80%  
sides 
2sided


lower limit 
0.37  
upper limit 
2.06  
Variability estimate 
Standard error of the mean


Dispersion value 
0.656


Notes [49]  1sided pvalue 

Statistical analysis title 
Partial Mayo Scores (Week 16)  
Statistical analysis description 
Cohort 3 MP versus Cohort 3 PP (Week 16)


Comparison groups 
Cohort 3: MultiStem 750, Placebo v Cohort 3: Placebo, Placebo


Number of subjects included in analysis 
46


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.75 ^{[50]}  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.43


Confidence interval 

level 
80%  
sides 
2sided


lower limit 
0.39  
upper limit 
1.25  
Variability estimate 
Standard error of the mean


Dispersion value 
0.635


Notes [50]  1sided pvalue 

Statistical analysis title 
Partial Mayo Scores (Week 16)  
Statistical analysis description 
Cohort 3 PM versus Cohort 3 PP (Week 16)


Comparison groups 
Cohort 3: Placebo, MultiStem 750 v Cohort 3: Placebo, Placebo


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.85 ^{[51]}  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.73


Confidence interval 

level 
80%  
sides 
2sided


lower limit 
0.16  
upper limit 
1.63  
Variability estimate 
Standard error of the mean


Dispersion value 
0.692


Notes [51]  1sided pvalue 


End point title 
Change From Baseline in Biopsy Histology Scores at Week 8  
End point description 
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; 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 4point scale (higher scores indicate more severe disease).


End point type 
Secondary


End point timeframe 
Baseline and Week 8




Statistical analysis title 
Biopsy Histology Scores (Week 8)  
Statistical analysis description 
Pooled MultiStem versus Pooled Placebo


Comparison groups 
Cohort 3: MultiStem 750, MultiStem 750 v Cohort 3: MultiStem 750, Placebo v Cohort 3: Placebo, MultiStem 750 v Cohort 3: Placebo, Placebo


Number of subjects included in analysis 
88


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.75 ^{[52]}  
Method 
ANCOVA  
Parameter type 
Mean difference (final values)  
Point estimate 
0.52


Confidence interval 

level 
80%  
sides 
2sided


lower limit 
0.46  
upper limit 
1.49  
Variability estimate 
Standard error of the mean


Dispersion value 
0.753


Notes [52]  1sided pvalue 


End point title 
Change From Baseline in PatientReported Rectal Bleeding up to Week 16  
End point description 
Patientreported 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.


End point type 
Secondary


End point timeframe 
Baseline and Week 16




Statistical analysis title 
PatientReported Rectal Bleeding up to Week 16  
Statistical analysis description 
Pooled MultiStem versus Pooled Placebo (Week 4)


Comparison groups 
Cohort 3: MultiStem 750, MultiStem 750 v Cohort 3: MultiStem 750, Placebo v Cohort 3: Placebo, MultiStem 750 v Cohort 3: Placebo, Placebo


Number of subjects included in analysis 
88


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.51 ^{[53]}  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0


Confidence interval 

level 
80%  
sides 
2sided


lower limit 
0.18  
upper limit 
0.19  
Variability estimate 
Standard error of the mean


Dispersion value 
0.144


Notes [53]  1sided pvalue 

Statistical analysis title 
PatientReported Rectal Bleeding up to Week 16  
Statistical analysis description 
Pooled MultiStem versus Pooled Placebo (Week 8)


Comparison groups 
Cohort 3: MultiStem 750, MultiStem 750 v Cohort 3: MultiStem 750, Placebo v Cohort 3: Placebo, MultiStem 750 v Cohort 3: Placebo, Placebo


Number of subjects included in analysis 
88


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.62 ^{[54]}  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.05


Confidence interval 

level 
80%  
sides 
2sided


lower limit 
0.16  
upper limit 
0.25  
Variability estimate 
Standard error of the mean


Dispersion value 
0.158


Notes [54]  1sided pvalue 

Statistical analysis title 
PatientReported Rectal Bleeding up to Week 16  
Statistical analysis description 
Cohort 3 MM versus Cohort 3 PP (Week 12)


Comparison groups 
Cohort 3: MultiStem 750, MultiStem 750 v Cohort 3: Placebo, Placebo


Number of subjects included in analysis 
44


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.29 ^{[55]}  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.12


Confidence interval 

level 
80%  
sides 
2sided


lower limit 
0.39  
upper limit 
0.16  
Variability estimate 
Standard error of the mean


Dispersion value 
0.213


Notes [55]  1sided pvalue 

Statistical analysis title 
PatientReported Rectal Bleeding up to Week 16  
Statistical analysis description 
Cohort 3 MP versus Cohort 3 PP (Week 12)


Comparison groups 
Cohort 3: MultiStem 750, Placebo v Cohort 3: Placebo, Placebo


Number of subjects included in analysis 
46


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.74 ^{[56]}  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.13


Confidence interval 

level 
80%  
sides 
2sided


lower limit 
0.14  
upper limit 
0.4  
Variability estimate 
Standard error of the mean


Dispersion value 
0.209


Notes [56]  1sided pvalue 

Statistical analysis title 
PatientReported Rectal Bleeding up to Week 16  
Statistical analysis description 
Cohort 3 PM versus Cohort 3 PP (Week 12)


Comparison groups 
Cohort 3: Placebo, MultiStem 750 v Cohort 3: Placebo, Placebo


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.36 ^{[57]}  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.08


Confidence interval 

level 
80%  
sides 
2sided


lower limit 
0.37  
upper limit 
0.21  
Variability estimate 
Standard error of the mean


Dispersion value 
0.226


Notes [57]  1sided pvalue 

Statistical analysis title 
PatientReported Rectal Bleeding up to Week 16  
Statistical analysis description 
Cohort 3 MM versus Cohort 3 PP (Week 16)


Comparison groups 
Cohort 3: MultiStem 750, MultiStem 750 v Cohort 3: Placebo, Placebo


Number of subjects included in analysis 
44


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.56 ^{[58]}  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.04


Confidence interval 

level 
80%  
sides 
2sided


lower limit 
0.26  
upper limit 
0.34  
Variability estimate 
Standard error of the mean


Dispersion value 
0.234


Notes [58]  1sided pvalue 

Statistical analysis title 
PatientReported Rectal Bleeding up to Week 16  
Statistical analysis description 
Cohort 3 MP versus Cohort 3 PP (Week 16)


Comparison groups 
Cohort 3: MultiStem 750, Placebo v Cohort 3: Placebo, Placebo


Number of subjects included in analysis 
46


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.18 ^{[59]}  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.21


Confidence interval 

level 
80%  
sides 
2sided


lower limit 
0.51  
upper limit 
0.09  
Variability estimate 
Standard error of the mean


Dispersion value 
0.231


Notes [59]  1sided pvalue 

Statistical analysis title 
PatientReported Rectal Bleeding up to Week 16  
Statistical analysis description 
Cohort 3 PM versus Cohort 3 PP (Week 16)


Comparison groups 
Cohort 3: Placebo, MultiStem 750 v Cohort 3: Placebo, Placebo


Number of subjects included in analysis 
40


Analysis specification 
Prespecified


Analysis type 
other  
Pvalue 
= 0.31 ^{[60]}  
Method 
Mixed models analysis  
Parameter type 
Mean difference (final values)  
Point estimate 
0.12


Confidence interval 

level 
80%  
sides 
2sided


lower limit 
0.45  
upper limit 
0.2  
Variability estimate 
Standard error of the mean


Dispersion value 
0.25


Notes [60]  1sided pvalue 


Adverse events information


Timeframe for reporting adverse events 
Baseline up to 28 days after last study drug administration.


Adverse event reporting additional description 
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 subject and as nonserious in another, or 1 subject may have experienced both an AE and SAE during the study. All treated subjects were included in the analysis.


Assessment type 
Nonsystematic  
Dictionary used for adverse event reporting


Dictionary name 
MedDRA  
Dictionary version 
17.1


Reporting groups


Reporting group title 
Cohort 1: Placebo, MultiStem 300


Reporting group description 
Subjects received a single dose (Day 1) or 3 doses (Day 1, Week 1, Week 2) of placebo infusion, followed by a single dose of MultiStem 300 Million Cells infusion at Week 8.  
Reporting group title 
Cohort 1: MultiStem 300, Placebo


Reporting group description 
Subjects received a single dose of MultiStem 300 Million Cells infusion on Day 1, followed by a single dose of placebo infusion at Week 8.  
Reporting group title 
Cohort 2: Placebo, MultiStem 750


Reporting group description 
Subjects received a single dose of placebo infusion on Day 1, followed by a single dose of MultiStem 750 Million Cells infusion at Week 8.  
Reporting group title 
Cohort 1: MultiStem 300 (x3), Placebo


Reporting group description 
Subjects received up to 3 doses of MultiStem 300 Million Cells infusion (Day 1, Week, Week 2), followed by a single dose of placebo infusion at Week 8.  
Reporting group title 
Cohort 3: MultiStem 750, MultiStem 750


Reporting group description 
Subjects received a single dose of MultiStem 750 Million Cells infusion on Day 1, followed by a single dose of MultiStem 750 Million Cells infusion at Week 8.  
Reporting group title 
Cohort 2: MultiStem 750, Placebo


Reporting group description 
Subjects received a single dose of MultiStem 750 Million Cells infusion on Day 1, followed by a single dose of placebo infusion at Week 8.  
Reporting group title 
Cohort 3: MultiStem 750, Placebo


Reporting group description 
Subjects received a single dose of MultiStem 750 Million Cells infusion on Day 1, followed by a single dose of placebo infusion at Week 8.  
Reporting group title 
Cohort 3: Placebo, MultiStem 750


Reporting group description 
Subjects received a single dose of placebo infusion on Day 1, followed by a single dose of MultiStem 750 Million Cells infusion at Week 8.  
Reporting group title 
Cohort 3: Placebo, Placebo


Reporting group description 
Subjects received a single dose of placebo infusion on Day 1, followed by a single dose of placebo infusion at Week 8.  


Frequency threshold for reporting nonserious adverse events: 5%  


Notes [1]  The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal. Justification: This AE is gender specific event. The percentages of gender specific events are calculated using the corresponding gender count as denominator. 


Substantial protocol amendments (globally) 

Were there any global substantial amendments to the protocol? Yes  
Date 
Amendment 

05 Oct 2012 
Interim analysis for futility was added. 

Interruptions (globally) 

Were there any global interruptions to the trial? No  
Limitations and caveats 

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.  
None reported 