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Cancer Vaccine Targeting Brachyury Protein in Tumors

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ClinicalTrials.gov Identifier: NCT01519817
Recruitment Status : Completed
First Posted : January 27, 2012
Results First Posted : July 31, 2017
Last Update Posted : January 29, 2018
Sponsor:
Information provided by (Responsible Party):
James Gulley, M.D., National Cancer Institute (NCI)

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Neoplasms
Malignant Solid Tumors
Colon Neoplasms
Adenocarcinoma
Intervention Biological: GI-6301 (Yeast Brachyury Vaccine)
Enrollment 34

Recruitment Details  
Pre-assignment Details  
Arm/Group Title 4 YU (Dose Level 1) 16 YU (Dose Level 2) 40 YU (Dose Level 3) 80 YU (Dose Level 4)
Hide Arm/Group Description Yeast-Brachyury vaccine will be administered subcutaneously at 4 sites on 7 visits, then monthly until patients meet off-treatment criteria. Yeast-Brachyury vaccine will be administered subcutaneously at 4 sites on 7 visits, then monthly until patients meet off-treatment criteria. Yeast-Brachyury vaccine will be administered subcutaneously at 4 sites on 7 visits, then monthly until patients meet off-treatment criteria. Yeast-Brachyury vaccine will be administered subcutaneously at 4 sites on 7 visits, then monthly until patients meet off-treatment criteria.
Period Title: Overall Study
Started 4 3 16 11
Completed 3 3 16 10
Not Completed 1 0 0 1
Reason Not Completed
Withdrawal by Subject             1             0             0             0
Off study due to infection             0             0             0             1
Arm/Group Title All Participants
Hide Arm/Group Description

All participants who received at least one dose of 4YU, 16YU, 40YU or 80YU.

Yeast-Brachyury vaccine will be administered subcutaneously at 4 sites on 7 visits, then monthly until patients meet off-treatment criteria.

GI-6301 (Yeast Brachyury Vaccine): GI-6301 is a heat-killed, recombinant yeast-based vaccine engineered to express the transcription factor, Brachyury. The Brachyury gene is used to transfect the parental yeast strain (S. cerevisiae W303 - a haploid strain with known mutations from wildtype yeast) to produce the final recombinant vaccine product.

Overall Number of Baseline Participants 34
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 34 participants
<=18 years
0
   0.0%
Between 18 and 65 years
24
  70.6%
>=65 years
10
  29.4%
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 34 participants
58
(32 to 79)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 34 participants
Female
15
  44.1%
Male
19
  55.9%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 34 participants
American Indian or Alaska Native
0
   0.0%
Asian
3
   8.8%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
1
   2.9%
White
30
  88.2%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Hispanic or Latino Number Analyzed 34 participants
0
   0.0%
Not Hispanic or Latino Number Analyzed 34 participants
33
  97.1%
Mexican, Puerto Rican, Cuban Central or So. Americ Number Analyzed 34 participants
1
   2.9%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 34 participants
34
 100.0%
Eastern Cooperative Oncology Group (ECOG) Performance Status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 34 participants
0
14
  41.2%
1
20
  58.8%
[1]
Measure Description: ECOG: 0 is normal activity. Fully active, able to carry on all pre-disease performance without restriction. 1 is symptoms, but ambulatory. Restricted in physically strenuous activity, but ambulatory and bale to carry out work of a light or sedentary nature (e.g., light housework, office work).
Tumor Type  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 34 participants
Colorectal
11
  32.4%
Chordoma
11
  32.4%
Breast
5
  14.7%
Pancreatic
3
   8.8%
Prostate
2
   5.9%
Urothelial
1
   2.9%
Lung
1
   2.9%
Disease at Study Entry   [1] [2] 
Measure Type: Count of Participants
Unit of measure:  Participants
Carcinomas Number Analyzed 23 participants
Stable disease
1
   4.3%
Progressive disease
22
  95.7%
Chordomas Number Analyzed 11 participants
Stable disease
2
  18.2%
Progressive disease
9
  81.8%
[1]
Measure Description: Stable disease does not meet criteria for complete response (disappearance of all lesions; no new lesions), partial response (≥30% decrease in the sum of greatest diameters; no new lesions), or progressive disease. Progressive disease is ≥20% increase in the sum of greatest diameters; new lesions.
[2]
Measure Analysis Population Description: 23 participants with carcinomas (solid tumors) and 11 participants with chordomas.
Prior Cytotoxic Regimens   [1] [2] 
Measure Type: Count of Participants
Unit of measure:  Participants
0 Number Analyzed 23 participants
1
   4.3%
1 regimen Number Analyzed 23 participants
2
   8.7%
2 regimens Number Analyzed 23 participants
8
  34.8%
≥3 regimens Number Analyzed 23 participants
12
  52.2%
[1]
Measure Description: Cytotoxic (i.e. poisonous to cancer cells)
[2]
Measure Analysis Population Description: The module refers to 23 participants with carcinomas (solid tumors).
Tumor Anatomical Location   [1] [2] 
Measure Type: Count of Participants
Unit of measure:  Participants
Sacral Number Analyzed 11 participants
6
  54.5%
Clival Number Analyzed 11 participants
3
  27.3%
Spinal Number Analyzed 11 participants
2
  18.2%
[1]
Measure Description: Sacral (i.e., sacrum), spinal (i.e., backbone), and clival (i.e. base of skull).
[2]
Measure Analysis Population Description: The module refers to 11 participants with chordomas.
Prior Therapy   [1] [2] 
Measure Type: Count of Participants
Unit of measure:  Participants
Surgery Number Analyzed 11 participants
11
 100.0%
Radiotherapy Number Analyzed 11 participants
11
 100.0%
Systemic therapy Number Analyzed 11 participants
5
  45.5%
[1]
Measure Description: Surgery, radiotherapy and systemic therapy use surgical procedures, targeted therapy with radiation, steroids, and/or other immunosuppressive agents in an attempt to suppress one or more growing lesions.
[2]
Measure Analysis Population Description: The module refers to 11 participants with chordomas.
1.Primary Outcome
Title Number of Participants With Brachyury-Specific T-cell Responses
Hide Description A fluorescense activated cell sorting (FACS)-based assay for cluster of differentiation 4 (CD4) or cluster of differentiation 8 (CD8) T-cells expressing the cytokines interferon (IFN) gamma, interleukin 2 (IL2), and tumor necrosis factor (TNF) alpha, and/or cluster of differentiation 107a (CD107a) (a marker for lytic potential) was used to determine the numbers of participants showing development or enhancement of the level of brachyury-specific T-cells after vaccination.
Time Frame Baseline (pre-vaccination) and approximately day 84 (after 6 vaccinations)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Sufficient peripheral blood mononuclear cells (PBMCs) were available before and after vaccination from 31 of 34 patients to analyze brachyury-specific CD4 and CD8 T-cell responses.
Arm/Group Title 4 YU (Dose Level 1) 16 YU (Dose Level 2) 40 YU (Dose Level 3) 80 YU (Dose Level 4)
Hide Arm/Group Description:
Yeast-Brachyury vaccine will be administered subcutaneously at 4 sites on 7 visits, then monthly until patients meet off-treatment criteria.
Yeast-Brachyury vaccine will be administered subcutaneously at 4 sites on 7 visits, then monthly until patients meet off-treatment criteria.
Yeast-Brachyury vaccine will be administered subcutaneously at 4 sites on 7 visits, then monthly until patients meet off-treatment criteria.
Yeast-Brachyury vaccine will be administered subcutaneously at 4 sites on 7 visits, then monthly until patients meet off-treatment criteria.
Overall Number of Participants Analyzed 3 3 16 9
Measure Type: Count of Participants
Unit of Measure: Participants
CD107a + CD4 T-cell response
1
  33.3%
0
   0.0%
4
  25.0%
1
  11.1%
IFN gamma + CD4 T-cell response
1
  33.3%
0
   0.0%
3
  18.8%
2
  22.2%
IL2 + CD4 T-cell response
0
   0.0%
0
   0.0%
3
  18.8%
3
  33.3%
TNF alpha + CD4 T-cell response
0
   0.0%
1
  33.3%
6
  37.5%
2
  22.2%
CD107a + CD8 T-cell response
0
   0.0%
0
   0.0%
3
  18.8%
4
  44.4%
IFN gamma + CD8 T-cell response
0
   0.0%
0
   0.0%
3
  18.8%
2
  22.2%
IL2 + CD8 T-cell response
0
   0.0%
0
   0.0%
0
   0.0%
1
  11.1%
TNF alpha + CD8 T-cell response
0
   0.0%
0
   0.0%
2
  12.5%
3
  33.3%
Any T-cell response
1
  33.3%
1
  33.3%
8
  50.0%
7
  77.8%
2.Primary Outcome
Title Count of Participants With Adverse Events of Escalating Doses of Yeast Brachyury ( GI- 6301) Vaccine
Hide Description Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. A non-serious adverse event is any untoward medical occurrence.
Time Frame 4 years and 25 days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 4 YU (Dose Level 1) 16 YU (Dose Level 2) 40 YU (Dose Level 3) 80 YU (Dose Level 4)
Hide Arm/Group Description:
Yeast-Brachyury vaccine will be administered subcutaneously at 4 sites on 7 visits, then monthly until patients meet off-treatment criteria.
Yeast-Brachyury vaccine will be administered subcutaneously at 4 sites on 7 visits, then monthly until patients meet off-treatment criteria.
Yeast-Brachyury vaccine will be administered subcutaneously at 4 sites on 7 visits, then monthly until patients meet off-treatment criteria.
Yeast-Brachyury vaccine will be administered subcutaneously at 4 sites on 7 visits, then monthly until patients meet off-treatment criteria.
Overall Number of Participants Analyzed 4 3 16 11
Measure Type: Count of Participants
Unit of Measure: Participants
4
 100.0%
3
 100.0%
16
 100.0%
10
  90.9%
3.Secondary Outcome
Title Number of Participants With a Clinical Benefit Assessed by the Response Evaluation Criteria in Solid Tumors (RECIST)
Hide Description Clinical benefit is defined as partial response (PR) or stable disease (SD) and was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Partial response is ≥30% decrease in the sum of greatest diameters/no new lesions. Progressive disease is ≥20% increase in the sum of greatest diameters/new lesions. Stable disease does not meet criteria for complete response (disappearance of all lesions; no new lesions), partial response, or progressive disease.
Time Frame 3 and 5 months restaging
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
One participant was not evaluable and came off study due to infection prior to restaging. Two participants were not evaluable due to withdrawal from the study or lack of measurable disease. Three patients with stable disease at 3 months elected to pursue alternate treatment and did not have 5 month restaging.
Arm/Group Title 4 YU (Dose Level 1) 16 YU (Dose Level 2) 40 YU (Dose Level 3) 80 YU (Dose Level 4)
Hide Arm/Group Description:
Yeast-Brachyury vaccine will be administered subcutaneously at 4 sites on 7 visits, then monthly until patients meet off-treatment criteria.
Yeast-Brachyury vaccine will be administered subcutaneously at 4 sites on 7 visits, then monthly until patients meet off-treatment criteria.
Yeast-Brachyury vaccine will be administered subcutaneously at 4 sites on 7 visits, then monthly until patients meet off-treatment criteria.
Yeast-Brachyury vaccine will be administered subcutaneously at 4 sites on 7 visits, then monthly until patients meet off-treatment criteria.
Overall Number of Participants Analyzed 4 3 16 11
Measure Type: Count of Participants
Unit of Measure: Participants
Stable disease at 3 months
3
  75.0%
0
   0.0%
8
  50.0%
6
  54.5%
Stable disease at 5 months
2
  50.0%
0
   0.0%
4
  25.0%
3
  27.3%
Partial response at 3 months
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Partial response at 5 months
0
   0.0%
0
   0.0%
1
   6.3%
0
   0.0%
Progressive disease at 3 months
1
  25.0%
3
 100.0%
8
  50.0%
5
  45.5%
Progressive disease at 5 months
1
  25.0%
0
   0.0%
3
  18.8%
0
   0.0%
4.Secondary Outcome
Title Changes in Immune Cell Subsets in Peripheral Blood Mononuclear Cells (PBMC)
Hide Description Blood samples will be collected via apheresis and analyzed by multicolor flow cytometry in PBMCs for cluster of differentiation 4 (CD4), cluster of differentiation 8 (CD8), Natural Killer (NK), Natural Killer T (NKT), conventional dendritic cell (cDC), plasmacytoid dendritic cell (pDC), myeloid-derived suppressor cell (MDSC), Tregs, CD4 central memory (CD4 CM), CD4 effector memory (CD4 EM), CD4 terminal effector memory (CD4 EMRA), CD4 naïve, CD8 CM, CD8 EM, CD8 EMRA, and CD8 naïve cells. Significance of changes in immune cells was determined by p value (Wilcoxon test) and the median and interquartile range of data.
Time Frame Pre (Baseline) and Day 85 after 6 vaccinations
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Due to insufficient samples at some time points in some patients, all participants were not analyzed in dose levels 2, 3 and 4; thus a statistical analysis was not performed.
Arm/Group Title 4 YU (Dose Level 1) 16 YU (Dose Level 2) 40 YU (Dose Level 3) 80 YU (Dose Level 4)
Hide Arm/Group Description:
Yeast-Brachyury vaccine will be administered subcutaneously at 4 sites on 7 visits, then monthly until patients meet off-treatment criteria.
Yeast-Brachyury vaccine will be administered subcutaneously at 4 sites on 7 visits, then monthly until patients meet off-treatment criteria.
Yeast-Brachyury vaccine will be administered subcutaneously at 4 sites on 7 visits, then monthly until patients meet off-treatment criteria.
Yeast-Brachyury vaccine will be administered subcutaneously at 4 sites on 7 visits, then monthly until patients meet off-treatment criteria.
Overall Number of Participants Analyzed 4 2 13 9
Median (Inter-Quartile Range)
Unit of Measure: percentage of PBMC
Median CD4 Pre
37.70
(24.11 to 46.36)
43.57
(40.26 to 46.87)
29.30
(24.65 to 39.77)
33.58
(26.84 to 39.92)
Median CD4 d85
38.61
(24.44 to 47.73)
33.44
(33.37 to 33.52)
34.29
(25.56 to 37.44)
27.99
(25.85 to 39.38)
Median CD8 Pre
15.87
(8.26 to 16.86)
14.77
(3.49 to 26.04)
15.96
(10.76 to 19.48)
13.76
(10.31 to 19.77)
Median CD8 d85
15.67
(9.102 to 16.57)
13.63
(4.123 to 23.14)
15.42
(10.96 to 22.44)
16.02
(10.57 to 25.5)
Median B cells Pre
7.05
(6.19 to 10.07)
11.02
(9.92 to 12.11)
8.97
(3.54 to 12.13)
7.82
(3.13 to 12.07)
Median B cells d85
6.93
(6.16 to 10.58)
9.78
(7.95 to 11.62)
9.10
(5.07 to 12.17)
8.77
(3.78 to 10.72)
Median Natural Killer (NK) Pre
5.21
(4.14 to 6.94)
6.57
(3.27 to 9.87)
5.72
(3.13 to 8.51)
5.89
(4.59 to 9.14)
Median Natural Killer (NK) d85
5.72
(4.03 to 7.39)
8.41
(5.50 to 11.31)
4.22
(3.97 to 10.07)
9.14
(5.95 to 11.4)
Median Natural Killer T cell (NKT) Pre
1.00
(0.65 to 4.21)
1.70
(0.46 to 2.94)
1.27
(0.62 to 2.81)
2.24
(0.59 to 4.39)
Median Natural Killer T cell (NKT) d85
1.25
(0.67 to 4.75)
2.46
(0.51 to 4.40)
1.19
(0.58 to 3.15)
2.53
(0.77 to 5.86)
Median cDC Pre
0.25
(0.14 to 0.28)
0.14
(0.11 to 0.17)
0.23
(0.20 to 0.37)
0.17
(0.16 to 0.35)
Median cDC d85
0.18
(0.14 to 0.23)
0.17
(0.16 to 0.19)
0.21
(0.18 to 0.34)
0.19
(0.09 to 0.23)
Median pDC Pre
0.25
(0.20 to 0.37)
0.17
(0.09 to 0.24)
0.23
(0.17 to 0.36)
0.23
(0.11 to 0.31)
Median pDC d85
0.32
(0.27 to 0.38)
0.26
(0.08 to 0.44)
0.27
(0.18 to 0.35)
0.23
(0.14 to 0.40)
Median MDSC Pre
10.98
(2.96 to 19.19)
8.53
(4.30 to 12.76)
8.47
(5.98 to 14.54)
13.73
(5.41 to 17.61)
Median MDSC d85
11.41
(4.82 to 18.78)
10.78
(5.98 to 15.58)
7.55
(4.95 to 12.16)
12.77
(6.64 to 14.23)
Median Treg Pre
0.77
(0.66 to 0.90)
0.90
(0.68 to 1.13)
1.25
(0.73 to 1.74)
1.07
(0.55 to 1.60)
Median Treg d85
0.81
(0.78 to 1.03)
0.80
(0.42 to 1.17)
1.12
(0.83 to 1.71)
1.00
(0.45 to 1.41)
Median CD4 EM Pre
10.58
(8.47 to 12.73)
12.09
(9.67 to 14.51)
13.14
(10.67 to 14.82)
11.31
(8.49 to 15.97)
Median CD4 EM d85
8.92
(7.49 to 13.48)
10.72
(9.20 to 12.25)
12.50
(11.33 to 13.63)
9.76
(7.21 to 15.68)
Median CD4 CM Pre
17.29
(8.59 to 21.10)
23.20
(12.62 to 33.79)
12.36
(9.16 to 17.44)
12.07
(7.52 to 16.56)
Median CD4 CM d85
18.80
(9.75 to 24.37)
16.51
(10.97 to 22.06)
12.78
(10.53 to 17.98)
11.36
(6.00 to 14.40)
Median CD4 EMRA Pre
0.32
(0.28 to 1.96)
0.68
(0.21 to 1.15)
0.34
(0.26 to 0.90)
0.28
(0.21 to 1.04)
Median CD4 EMRA d85
0.34
(0.26 to 0.70)
0.83
(0.24 to 1.43)
0.28
(0.23 to 0.56)
0.38
(0.21 to 1.75)
Median CD4 naive Pre
10.28
(4.23 to 12.36)
7.57
(3.23 to 11.91)
3.78
(2.47 to 6.90)
4.49
(2.56 to 10.22)
Median CD4 naive d85
8.48
(4.14 to 12.76)
5.41
(2.08 to 8.73)
3.99
(3.49 to 7.51)
6.08
(3.15 to 9.55)
Median CD8 EM Pre
3.20
(2.33 to 6.85)
2.70
(1.54 to 3.86)
7.19
(4.45 to 8.92)
5.23
(4.21 to 7.64)
Median CD8 EM d85
3.44
(2.85 to 6.87)
3.33
(2.61 to 4.06)
6.60
(4.12 to 10.78)
6.11
(3.91 to 7.30)
Median CD8 CM Pre
1.03
(0.61 to 2.70)
1.05
(0.80 to 1.30)
1.16
(0.56 to 1.48)
1.00
(0.53 to 1.38)
Median CD8 CM d85
1.31
(0.81 to 2.43)
0.86
(0.53 to 1.19)
0.95
(0.80 to 1.44)
0.88
(0.32 to 1.26)
Median CD8 EMRA Pre
3.01
(1.22 to 8.46)
2.51
(0.63 to 4.39)
2.60
(1.36 to 9.95)
5.81
(2.26 to 8.75)
Median CD8 EMRA d85
2.84
(1.40 to 7.35)
3.24
(0.69 to 5.80)
3.31
(1.14 to 10.71)
5.06
(3.11 to 10.83)
Median CD8 naive Pre
3.47
(2.50 to 5.60)
8.51
(0.53 to 16.49)
2.43
(0.92 to 5.25)
3.71
(2.86 to 5.92)
Median CD8 naive d85
3.28
(2.58 to 6.21)
6.20
(0.30 to 12.09)
3.12
(1.00 to 5.82)
3.44
(2.06 to 5.45)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 4 YU (Dose Level 1), 40 YU (Dose Level 3), 80 YU (Dose Level 4)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.5221
Comments The reported p-value is representative of the changes in levels of all CD4 cells at dose levels 1, 3, and 4. We could not do dose level 2 as we only had data on 2 patients and need an n>2 to do paired analyses.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 4 YU (Dose Level 1)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.25
Comments The reported p-value is representative of the changes in levels of CD4 cells at dose level 1.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 40 YU (Dose Level 3)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.50
Comments The reported p-value is representative of the changes in levels of CD4 cells at dose level 3.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 80 YU (Dose Level 4)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.16
Comments The reported p-value is representative of the changes in levels of CD4 cells at dose level 4.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection 4 YU (Dose Level 1), 40 YU (Dose Level 3), 80 YU (Dose Level 4)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.8665
Comments The reported p-value is representative of the changes in levels of all CD8 cells at dose levels 1, 3, and 4. We could not do dose level 2 as we only had data on 2 patients and need an n>2 to do paired analyses.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection 4 YU (Dose Level 1)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.88
Comments The reported p-value is representative of the changes in levels of all CD8 cells at dose levels 1, 3, and 4. We could not do dose level 2 as we only had data on 2 patients and need an n>2 to do paired analyses.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection 40 YU (Dose Level 3)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.84
Comments The reported p-value is representative of the changes in levels of CD8 cells at dose level 3.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection 80 YU (Dose Level 4)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.57
Comments The reported p-value is representative of the changes in levels of CD8 cells at dose level 4.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection 4 YU (Dose Level 1), 40 YU (Dose Level 3), 80 YU (Dose Level 4)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.3052
Comments The reported p-value is representative of the changes in levels of all B cells at dose levels 1, 3, and 4. We could not do dose level 2 as we only had data on 2 patients and need an n>2 to do paired analyses.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection 4 YU (Dose Level 1)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value >0.9999
Comments The reported p-value is representative of the changes in levels of B cells at dose level 1.
Method Wilcoxon test
Comments The reported p-value is representative of the changes in levels of B cells at dose level 1.
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection 40 YU (Dose Level 3)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.13
Comments The reported p-value is representative of the changes in levels of B cells at dose level 3.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection 80 YU (Dose Level 4)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.65
Comments The reported p-value is representative of the changes in levels of B cells at dose level 4.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 13 Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection 4 YU (Dose Level 1), 40 YU (Dose Level 3), 80 YU (Dose Level 4)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.0698
Comments The reported p-value is representative of the changes in levels of all NK cells at dose levels 1, 3, and 4. We could not do dose level 2 as we only had data on 2 patients and need an n>2 to do paired analyses.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 14 Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection 4 YU (Dose Level 1)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.63
Comments The reported p-value is representative of the changes in levels of NK cells at dose level 1.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 15 Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection 40 YU (Dose Level 3)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.74
Comments The reported p-value is representative of the changes in levels of NK cells at dose level 3.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 16 Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection 80 YU (Dose Level 4)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.13
Comments The reported p-value is representative of the changes in levels of NK cells at dose level 4.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 17 Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection 4 YU (Dose Level 1), 40 YU (Dose Level 3), 80 YU (Dose Level 4)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.0127
Comments The reported p-value is representative of the changes in levels of all NKT cells at dose levels 1, 3, and 4. We could not do dose level 2 as we only had data on 2 patients and need an n>2 to do paired analyses.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 18 Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection 4 YU (Dose Level 1)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.63
Comments The reported p-value is representative of the changes in levels of NKT cells at dose level 1.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 19 Hide Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection 40 YU (Dose Level 3)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.41
Comments The reported p-value is representative of the changes in levels of NKT cells at dose level 3.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 20 Hide Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection 80 YU (Dose Level 4)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.07
Comments The reported p-value is representative of the changes in levels of NKT cells at dose level 4.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 21 Hide Statistical Analysis 21
Statistical Analysis Overview Comparison Group Selection 4 YU (Dose Level 1), 40 YU (Dose Level 3), 80 YU (Dose Level 4)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.0654
Comments The reported p-value is representative of the changes in levels of all cDC cells at dose levels 1, 3, and 4. We could not do dose level 2 as we only had data on 2 patients and need an n>2 to do paired analyses.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 22 Hide Statistical Analysis 22
Statistical Analysis Overview Comparison Group Selection 4 YU (Dose Level 1)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.38
Comments The reported p-value is representative of the changes in levels of cDC cells at dose level 1.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 23 Hide Statistical Analysis 23
Statistical Analysis Overview Comparison Group Selection 40 YU (Dose Level 3)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.21
Comments The reported p-value is representative of the changes in levels of cDC cells at dose level 3.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 24 Hide Statistical Analysis 24
Statistical Analysis Overview Comparison Group Selection 80 YU (Dose Level 4)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.16
Comments The reported p-value is representative of the changes in levels of cDC cells at dose level 4.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 25 Hide Statistical Analysis 25
Statistical Analysis Overview Comparison Group Selection 4 YU (Dose Level 1), 40 YU (Dose Level 3), 80 YU (Dose Level 4)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.0457
Comments The reported p-value is representative of the changes in levels of all pDC cells at dose levels 1, 3, and 4. We could not do dose level 2 as we only had data on 2 patients and need an n>2 to do paired analyses.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 26 Hide Statistical Analysis 26
Statistical Analysis Overview Comparison Group Selection 4 YU (Dose Level 1)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.63
Comments The reported p-value is representative of the changes in levels of pDC cells at dose level 1.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 27 Hide Statistical Analysis 27
Statistical Analysis Overview Comparison Group Selection 40 YU (Dose Level 3)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.55
Comments The reported p-value is representative of the changes in levels of pDC cells at dose level 3.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 28 Hide Statistical Analysis 28
Statistical Analysis Overview Comparison Group Selection 80 YU (Dose Level 4)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.13
Comments The reported p-value is representative of the changes in levels of pDC cells at dose level 4.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 29 Hide Statistical Analysis 29
Statistical Analysis Overview Comparison Group Selection 4 YU (Dose Level 1), 40 YU (Dose Level 3), 80 YU (Dose Level 4)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.7114
Comments The reported p-value is representative of the changes in levels of all MDSC cells at dose levels 1, 3, and 4. We could not do dose level 2 as we only had data on 2 patients and need an n>2 to do paired analyses.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 30 Hide Statistical Analysis 30
Statistical Analysis Overview Comparison Group Selection 4 YU (Dose Level 1)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value >0.9999
Comments The reported p-value is representative of the changes in levels of MDSC cells at dose level 1.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 31 Hide Statistical Analysis 31
Statistical Analysis Overview Comparison Group Selection 40 YU (Dose Level 3)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.38
Comments The reported p-value is representative of the changes in levels of MDSC cells at dose level 3.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 32 Hide Statistical Analysis 32
Statistical Analysis Overview Comparison Group Selection 80 YU (Dose Level 4)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.91
Comments The reported p-value is representative of the changes in levels of MDSC cells at dose level 4.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 33 Hide Statistical Analysis 33
Statistical Analysis Overview Comparison Group Selection 4 YU (Dose Level 1), 40 YU (Dose Level 3), 80 YU (Dose Level 4)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.2666
Comments The reported p-value is representative of the changes in levels of all Treg cells at dose levels 1, 3, and 4. We could not do dose level 2 as we only had data on 2 patients and need an n>2 to do paired analyses.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 34 Hide Statistical Analysis 34
Statistical Analysis Overview Comparison Group Selection 4 YU (Dose Level 1)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.88
Comments The reported p-value is representative of the changes in levels of Treg cells at dose level 1.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 35 Hide Statistical Analysis 35
Statistical Analysis Overview Comparison Group Selection 40 YU (Dose Level 3)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.45
Comments The reported p-value is representative of the changes in levels of Treg cells at dose level 1.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 36 Hide Statistical Analysis 36
Statistical Analysis Overview Comparison Group Selection 80 YU (Dose Level 4)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.36
Comments The reported p-value is representative of the changes in levels of Treg cells at dose level 4.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 37 Hide Statistical Analysis 37
Statistical Analysis Overview Comparison Group Selection 4 YU (Dose Level 1), 40 YU (Dose Level 3), 80 YU (Dose Level 4)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.0076
Comments The reported p-value is representative of the changes in levels of all CD4 EM cells at dose levels 1, 3, and 4. We could not do dose level 2 as we only had data on 2 patients and need an n>2 to do paired analyses.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 38 Hide Statistical Analysis 38
Statistical Analysis Overview Comparison Group Selection 4 YU (Dose Level 1)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.38
Comments The reported p-value is representative of the changes in levels of CD4 EM cells at dose level 1.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 39 Hide Statistical Analysis 39
Statistical Analysis Overview Comparison Group Selection 40 YU (Dose Level 3)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.22
Comments The reported p-value is representative of the changes in levels of CD4 EM cells at dose level 3.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 40 Hide Statistical Analysis 40
Statistical Analysis Overview Comparison Group Selection 80 YU (Dose Level 4)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.10
Comments The reported p-value is representative of the changes in levels of CD4 EM cells at dose level 4.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 41 Hide Statistical Analysis 41
Statistical Analysis Overview Comparison Group Selection 4 YU (Dose Level 1), 40 YU (Dose Level 3), 80 YU (Dose Level 4)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.7144
Comments The reported p-value is representative of the changes in levels of all CD4 CM cells at dose levels 1, 3, and 4. We could not do dose level 2 as we only had data on 2 patients and need an n>2 to do paired analyses.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 42 Hide Statistical Analysis 42
Statistical Analysis Overview Comparison Group Selection 4 YU (Dose Level 1)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.13
Comments The reported p-value is representative of the changes in levels of CD4 CM cells at dose level 1.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 43 Hide Statistical Analysis 43
Statistical Analysis Overview Comparison Group Selection 40 YU (Dose Level 3)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.06
Comments The reported p-value is representative of the changes in levels of CD4 CM cells at dose level 3.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 44 Hide Statistical Analysis 44
Statistical Analysis Overview Comparison Group Selection 80 YU (Dose Level 4)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.13
Comments The reported p-value is representative of the changes in levels of CD4 CM cells at dose level 4.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 45 Hide Statistical Analysis 45
Statistical Analysis Overview Comparison Group Selection 4 YU (Dose Level 1), 40 YU (Dose Level 3), 80 YU (Dose Level 4)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.3741
Comments The reported p-value is representative of the changes in levels of all CD4 EMRA cells at dose levels 1, 3, and 4. We could not do dose level 2 as we only had data on 2 patients and need an n>2 to do paired analyses.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 46 Hide Statistical Analysis 46
Statistical Analysis Overview Comparison Group Selection 4 YU (Dose Level 1)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments The reported p-value is representative of the changes in levels of CD4 EMRA cells at dose level 1.
Statistical Test of Hypothesis P-Value 0.63
Comments [Not Specified]
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 47 Hide Statistical Analysis 47
Statistical Analysis Overview Comparison Group Selection 40 YU (Dose Level 3)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.13
Comments The reported p-value is representative of the changes in levels of CD4 EMRA cells at dose level 3.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 48 Hide Statistical Analysis 48
Statistical Analysis Overview Comparison Group Selection 80 YU (Dose Level 4)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value >0.9999
Comments The reported p-value is representative of the changes in levels of CD4 EMRA cells at dose level 4.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 49 Hide Statistical Analysis 49
Statistical Analysis Overview Comparison Group Selection 4 YU (Dose Level 1), 40 YU (Dose Level 3), 80 YU (Dose Level 4)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.3386
Comments The reported p-value is representative of the changes in levels of all CD4 naive cells at dose levels 1, 3, and 4. We could not do dose level 2 as we only had data on 2 patients and need an n>2 to do paired analyses.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 50 Hide Statistical Analysis 50
Statistical Analysis Overview Comparison Group Selection 4 YU (Dose Level 1)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.88
Comments The reported p-value is representative of the changes in levels of CD4 naive cells at dose level 1.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 51 Hide Statistical Analysis 51
Statistical Analysis Overview Comparison Group Selection 40 YU (Dose Level 3)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.0215
Comments The reported p-value is representative of the changes in levels of CD4 naive cells at dose level 3.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 52 Hide Statistical Analysis 52
Statistical Analysis Overview Comparison Group Selection 80 YU (Dose Level 4)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.65
Comments The reported p-value is representative of the changes in levels of CD4 naive cells at dose level 4.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 53 Hide Statistical Analysis 53
Statistical Analysis Overview Comparison Group Selection 4 YU (Dose Level 1), 40 YU (Dose Level 3), 80 YU (Dose Level 4)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.5076
Comments The reported p-value is representative of the changes in levels of all CD8 EM cells at dose levels 1, 3, and 4. We could not do dose level 2 as we only had data on 2 patients and need an n>2 to do paired analyses.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 54 Hide Statistical Analysis 54
Statistical Analysis Overview Comparison Group Selection 4 YU (Dose Level 1)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.63
Comments The reported p-value is representative of the changes in levels of CD8 EM cells at dose level 1.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 55 Hide Statistical Analysis 55
Statistical Analysis Overview Comparison Group Selection 40 YU (Dose Level 3)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.68
Comments The reported p-value is representative of the changes in levels of CD8 EM cells at dose level 3.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 56 Hide Statistical Analysis 56
Statistical Analysis Overview Comparison Group Selection 80 YU (Dose Level 4)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.73
Comments The reported p-value is representative of the changes in levels of CD8 EM cells at dose level 4.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 57 Hide Statistical Analysis 57
Statistical Analysis Overview Comparison Group Selection 4 YU (Dose Level 1), 40 YU (Dose Level 3), 80 YU (Dose Level 4)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.6577
Comments The reported p-value is representative of the changes in levels of all CD8 CM cells at dose levels 1, 3, and 4. We could not do dose level 2 as we only had data on 2 patients and need an n>2 to do paired analyses.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 58 Hide Statistical Analysis 58
Statistical Analysis Overview Comparison Group Selection 4 YU (Dose Level 1)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.88
Comments The reported p-value is representative of the changes in levels of CD8 CM cells at dose level 1.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 59 Hide Statistical Analysis 59
Statistical Analysis Overview Comparison Group Selection 40 YU (Dose Level 3)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.74
Comments The reported p-value is representative of the changes in levels of CD8 CM cells at dose level 3.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 60 Hide Statistical Analysis 60
Statistical Analysis Overview Comparison Group Selection 80 YU (Dose Level 4)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.20
Comments The reported p-value is representative of the changes in levels of CD8 CM cells at dose level 4.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 61 Hide Statistical Analysis 61
Statistical Analysis Overview Comparison Group Selection 4 YU (Dose Level 1), 40 YU (Dose Level 3), 80 YU (Dose Level 4)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.6295
Comments The reported p-value is representative of the changes in levels of all CD8 EMRA cells at dose levels 1, 3, and 4. We could not do dose level 2 as we only had data on 2 patients and need an n>2 to do paired analyses.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 62 Hide Statistical Analysis 62
Statistical Analysis Overview Comparison Group Selection 4 YU (Dose Level 1)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.63
Comments The reported p-value is representative of the changes in levels of CD8 EMRA cells at dose level 1.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 63 Hide Statistical Analysis 63
Statistical Analysis Overview Comparison Group Selection 40 YU (Dose Level 3)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value >0.999
Comments The reported p-value is representative of the changes in levels of CD8 EMRA cells at dose level 3.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 64 Hide Statistical Analysis 64
Statistical Analysis Overview Comparison Group Selection 80 YU (Dose Level 4)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.36
Comments The reported p-value is representative of the changes in levels of CD8 EMRA cells at dose level 4.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 65 Hide Statistical Analysis 65
Statistical Analysis Overview Comparison Group Selection 4 YU (Dose Level 1), 40 YU (Dose Level 3), 80 YU (Dose Level 4)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.8314
Comments The reported p-value is representative of the changes in levels of all CD8 naive cells at dose levels 1, 3, and 4. We could not do dose level 2 as we only had data on 2 patients and need an n>2 to do paired analyses.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 66 Hide Statistical Analysis 66
Statistical Analysis Overview Comparison Group Selection 4 YU (Dose Level 1)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments The reported p-value is representative of the changes in levels of CD8 naive cells at dose level 1.
Statistical Test of Hypothesis P-Value 0.63
Comments [Not Specified]
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 67 Hide Statistical Analysis 67
Statistical Analysis Overview Comparison Group Selection 40 YU (Dose Level 3)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.64
Comments The reported p-value is representative of the changes in levels of CD8 naive cells at dose level 3.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 68 Hide Statistical Analysis 68
Statistical Analysis Overview Comparison Group Selection 80 YU (Dose Level 4)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.30
Comments The reported p-value is representative of the changes in levels of CD8 naive cells at dose level 4.
Method Wilcoxon test
Comments [Not Specified]
5.Secondary Outcome
Title Changes in Serum Levels of Cytokines
Hide Description Blood samples were collected and changes in serum levels of cytokines interferon gamma (IFNg), Interleukin 10 (IL-10), Interleukin 12 (IL-12)p70, Interleukin 1b (IL-1b), Interleukin 2 (IL-2), Interleukin 6 (IL-6), Interleukin 8 (IL-8), and tumor necrosis factor (TNF) were assessed by the multiplexed mesoscale assay. Significance of changes in serum levels of cytokines was determined by p value (Wilcoxon test) and the median and interquartile range of data.
Time Frame Pre (Baseline) and Day 85 after 6 vaccinations
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Due to insufficient samples at some time points in some patients, all participants were not analyzed in dose levels 2, 3 and 4; thus a statistical analysis was not performed.
Arm/Group Title 4 YU (Dose Level 1) 16 YU (Dose Level 2) 40 YU (Dose Level 3) 80 YU (Dose Level 4)
Hide Arm/Group Description:
Yeast-Brachyury vaccine will be administered subcutaneously at 4 sites on 7 visits, then monthly until patients meet off-treatment criteria.
Yeast-Brachyury vaccine will be administered subcutaneously at 4 sites on 7 visits, then monthly until patients meet off-treatment criteria.
Yeast-Brachyury vaccine will be administered subcutaneously at 4 sites on 7 visits, then monthly until patients meet off-treatment criteria.
Yeast-Brachyury vaccine will be administered subcutaneously at 4 sites on 7 visits, then monthly until patients meet off-treatment criteria.
Overall Number of Participants Analyzed 4 2 12 9
Median (Inter-Quartile Range)
Unit of Measure: pg/ml
Median IFNg Pre
3.63
(2.47 to 6.12)
3.56
(2.99 to 4.13)
2.805
(1.97 to 3.6)
4.47
(4.05 to 7.48)
Median IFNg d85
2.64
(2.17 to 3.17)
2.83
(2.62 to 3.04)
2.84
(1.76 to 4.71)
4.9
(2.91 to 6.81)
Median IL-10 Pre
0.24
(0.17 to 0.54)
0.215
(0.2 to 0.23)
0.21
(0.17 to 0.28)
0.4
(0.31 to 0.47)
Median IL-10 d85
0.26
(0.23 to 0.39)
0.285
(0.28 to 0.29)
0.24
(0.18 to 0.31)
0.4
(0.26 to 0.52)
Median IL-12p70 Pre
0.2
(0.2 to 0.22)
0.22
(0.2 to 0.24)
0.2
(0.2 to 0.2)
0.2
(0.2 to 0.37)
Median IL-12p70 d85
0.2
(0.2 to 0.28)
0.2
(0.2 to 0.2)
0.2
(0.2 to 0.2)
0.2
(0.2 to 0.26)
Median IL-1b Pre
0.24
(0.24 to 1.15)
0.24
(0.24 to 0.24)
0.24
(0.24 to 0.24)
0.24
(0.24 to 2.52)
Median IL-1b d85
0.24
(0.24 to 0.25)
0.24
(0.24 to 0.24)
0.24
(0.24 to 0.24)
0.24
(0.24 to 0.89)
Median IL-2 Pre
0.64
(0.64 to 2.40)
0.64
(0.64 to 0.64)
0.64
(0.64 to 0.64)
0.64
(0.64 to 0.80)
Median IL-2 d85
0.64
(0.64 to 0.93)
0.64
(0.64 to 0.64)
0.64
(0.64 to 0.64)
0.64
(0.64 to 0.70)
Median IL-6 Pre
0.88
(0.71 to 2.85)
0.78
(0.66 to 0.9)
1.02
(0.52 to 1.3)
2.37
(0.69 to 15.3)
Median IL-6 d85
0.97
(0.74 to 1.23)
0.855
(0.76 to 0.95)
1.04
(0.54 to 1.97)
2.84
(0.90 to 4.84)
Median IL-8 Pre
56.45
(16.84 to 487.6)
43.87
(16.05 to 71.69)
37.49
(18 to 91.01)
63.52
(33.7 to 560.2)
Median IL-8 d85
33.29
(30.52 to 124.5)
61.85
(44.98 to 78.71)
43.27
(17.99 to 140.1)
73.21
(38.62 to 200.9)
Median TNF Pre
1.54
(1.19 to 8.19)
1.315
(1.24 to 1.39)
1.62
(1.25 to 2.26)
3.59
(2.19 to 9.24)
Median TNF d85
1.63
(1.45 to 1.81)
1.465
(1.23 to 1.7)
1.67
(1.38 to 2.07)
2.74
(2.26 to 3.77)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 4 YU (Dose Level 1)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.375
Comments The reported p-value is representative of the changes in levels of IFNg cytokines at dose level 1.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 4 YU (Dose Level 1), 40 YU (Dose Level 3), 80 YU (Dose Level 4)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.4808
Comments The reported p-value is representative of the changes in levels of all IFNg cytokines at dose levels 1, 3, and 4. We could not do dose level 2 as we only had data on 2 patients and need an n>2 to do paired analyses.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 40 YU (Dose Level 3)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.7334
Comments The reported p-value is representative of the changes in levels of IFNg cytokines at dose level 3.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 80 YU (Dose Level 4)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.7109
Comments The reported p-value is representative of the changes in levels of IFNg cytokines at dose level 4.
Method Wilcoxon
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection 4 YU (Dose Level 1), 40 YU (Dose Level 3), 80 YU (Dose Level 4)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.4347
Comments The reported p-value is representative of the changes in levels of all IL10 cytokines at dose levels 1, 3, and 4. We could not do dose level 2 as we only had data on 2 patients and need an n>2 to do paired analyses.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection 4 YU (Dose Level 1)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value >0.9999
Comments The reported p-value is representative of the changes in levels of IL10 cytokines at dose level 1.
Method Wilcoxon
Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection 40 YU (Dose Level 3)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.748
Comments The reported p-value is representative of the changes in levels of IL10 cytokines at dose level 3.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection 80 YU (Dose Level 4)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.8203
Comments [Not Specified]
Method Wilcoxon test
Comments The reported p-value is representative of the changes in levels of IL10 cytokines at dose level 4.
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection 4 YU (Dose Level 1), 40 YU (Dose Level 3), 80 YU (Dose Level 4)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.5625
Comments The reported p-value is representative of the changes in levels of all IL12p70 cytokines at dose levels 1, 3, and 4. We could not do dose level 2 as we only had data on 2 patients and need an n>2 to do paired analyses.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection 4 YU (Dose Level 1)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value >0.9999
Comments The reported p-value is representative of the changes in levels of IL12p70 cytokines at dose level 1.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection 40 YU (Dose Level 3)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value >0.9999
Comments The reported p-value is representative of the changes in levels of IL12p70 cytokines at dose level 3.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection 80 YU (Dose Level 4)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.5
Comments The reported p-value is representative of the changes in levels of IL12p70 cytokines at dose level 14
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 13 Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection 4 YU (Dose Level 1), 40 YU (Dose Level 3), 80 YU (Dose Level 4)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.6846
Comments The reported p-value is representative of the changes in levels of all IL1b cytokines at dose levels 1, 3, and 4. We could not do dose level 2 as we only had data on 2 patients and need an n>2 to do paired analyses.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 14 Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection 4 YU (Dose Level 1)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value >0.9999
Comments The reported p-value is representative of the changes in levels of IL1b cytokines at dose level 1.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 15 Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection 40 YU (Dose Level 3)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.5
Comments The reported p-value is representative of the changes in levels of IL1b cytokines at dose level 3.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 16 Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection 80 YU (Dose Level 4)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value >0.9999
Comments The reported p-value is representative of the changes in levels of IL1b cytokines at dose level 4.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 17 Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection 4 YU (Dose Level 1), 40 YU (Dose Level 3), 80 YU (Dose Level 4)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.4375
Comments The reported p-value is representative of the changes in levels of all IL-2 cytokines at dose levels 1, 3, and 4. We could not do dose level 2 as we only had data on 2 patients and need an n>2 to do paired analyses.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 18 Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection 4 YU (Dose Level 1)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value >0.9999
Comments The reported p-value is representative of the changes in levels of IL-2 cytokines at dose level 1.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 19 Hide Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection 40 YU (Dose Level 3)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value >0.9999
Comments The reported p-value is representative of the changes in levels of IL-2 cytokines at dose level 3.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 20 Hide Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection 80 YU (Dose Level 4)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.75
Comments The reported p-value is representative of the changes in levels of IL-2 cytokines at dose level 4.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 21 Hide Statistical Analysis 21
Statistical Analysis Overview Comparison Group Selection 4 YU (Dose Level 1), 40 YU (Dose Level 3), 80 YU (Dose Level 4)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.4525
Comments The reported p-value is representative of the changes in levels of all IL-6 cytokines at dose levels 1, 3, and 4. We could not do dose level 2 as we only had data on 2 patients and need an n>2 to do paired analyses.
Method Wilcoxon test
Comments The reported p-value is representative of the changes in levels of IL-6 cytokines at dose level 1.
Show Statistical Analysis 22 Hide Statistical Analysis 22
Statistical Analysis Overview Comparison Group Selection 4 YU (Dose Level 1)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.875
Comments The reported p-value is representative of the changes in levels of IL-6 cytokines at dose level 1.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 23 Hide Statistical Analysis 23
Statistical Analysis Overview Comparison Group Selection 40 YU (Dose Level 3)
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Type of Statistical Test Non-Inferiority
Comments The reported p-value is representative of the changes in levels of IL-6 cytokines at dose level 3.
Statistical Test of Hypothesis P-Value 0.4316
Comments [Not Specified]
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 24 Hide Statistical Analysis 24
Statistical Analysis Overview Comparison Group Selection 80 YU (Dose Level 4)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value >0.9999
Comments The reported p-value is representative of the changes in levels of IL-6 cytokines at dose level 4.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 25 Hide Statistical Analysis 25
Statistical Analysis Overview Comparison Group Selection 4 YU (Dose Level 1), 40 YU (Dose Level 3), 80 YU (Dose Level 4)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.9906
Comments The reported p-value is representative of the changes in levels of all IL-8 cytokines at dose levels 1, 3, and 4. We could not do dose level 2 as we only had data on 2 patients and need an n>2 to do paired analyses.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 26 Hide Statistical Analysis 26
Statistical Analysis Overview Comparison Group Selection 4 YU (Dose Level 1)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.625
Comments [Not Specified]
Method Wilcoxon test
Comments The reported p-value is representative of the changes in levels of IL-8 cytokines at dose level 1.
Show Statistical Analysis 27 Hide Statistical Analysis 27
Statistical Analysis Overview Comparison Group Selection 40 YU (Dose Level 3)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.791
Comments The reported p-value is representative of the changes in levels of IL-8 cytokines at dose level 3.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 28 Hide Statistical Analysis 28
Statistical Analysis Overview Comparison Group Selection 80 YU (Dose Level 4)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.8203
Comments The reported p-value is representative of the changes in levels of IL-8 cytokines at dose level 4.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 29 Hide Statistical Analysis 29
Statistical Analysis Overview Comparison Group Selection 4 YU (Dose Level 1), 40 YU (Dose Level 3), 80 YU (Dose Level 4)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value >0.9999
Comments The reported p-value is representative of the changes in levels of all TNF cytokines at dose levels 1, 3, and 4. We could not do dose level 2 as we only had data on 2 patients and need an n>2 to do paired analyses.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 30 Hide Statistical Analysis 30
Statistical Analysis Overview Comparison Group Selection 4 YU (Dose Level 1)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.875
Comments The reported p-value is representative of the changes in levels of TNF cytokines at dose level 1.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 31 Hide Statistical Analysis 31
Statistical Analysis Overview Comparison Group Selection 40 YU (Dose Level 3)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.9658
Comments The reported p-value is representative of the changes in levels of TNF cytokines at dose level 3.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 32 Hide Statistical Analysis 32
Statistical Analysis Overview Comparison Group Selection 80 YU (Dose Level 4)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.6523
Comments The reported p-value is representative of the changes in levels of TNF cytokines at dose level 4.
Method Wilcoxon test
Comments [Not Specified]
6.Secondary Outcome
Title Changes in Soluble Cluster of Differentiation 27 (sCD27)
Hide Description Blood samples were collected and changes in serum levels of soluble sCD27 were assessed by enzyme-linked immunosorbent assay (ELISA). Significance of changes in soluble sCD27 was determined by p value (Wilcoxon test) and the median and interquartile range of data.
Time Frame Pre (Baseline) and Day 85 after 6 vaccinations
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Due to insufficient samples at some time points in some patients, all participants were not analyzed in dose levels 2, 3 and 4; thus a statistical analysis was not performed.
Arm/Group Title 4 YU (Dose Level 1) 16 YU (Dose Level 2) 40 YU (Dose Level 3) 80 YU (Dose Level 4)
Hide Arm/Group Description:
Yeast-Brachyury vaccine will be administered subcutaneously at 4 sites on 7 visits, then monthly until patients meet off-treatment criteria.
Yeast-Brachyury vaccine will be administered subcutaneously at 4 sites on 7 visits, then monthly until patients meet off-treatment criteria.
Yeast-Brachyury vaccine will be administered subcutaneously at 4 sites on 7 visits, then monthly until patients meet off-treatment criteria.
Yeast-Brachyury vaccine will be administered subcutaneously at 4 sites on 7 visits, then monthly until patients meet off-treatment criteria.
Overall Number of Participants Analyzed 4 2 12 9
Median (Inter-Quartile Range)
Unit of Measure: U/ml
Median sCD27 Pre
99.07
(91.13 to 131)
98.63
(87.12 to 110.1)
97.47
(85.15 to 110.9)
128.4
(123.9 to 145.6)
Median sCD27 d85
97.17
(92.07 to 1112)
92.07
(83.3 to 100.8)
101.7
(98.85 to 105.1)
133.1
(129.7 to 155.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 4 YU (Dose Level 1), 40 YU (Dose Level 3), 80 YU (Dose Level 4)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.2901
Comments The reported p-value is representative of the changes in levels of all sCD27 cytokines at dose levels 1, 3, and 4. We could not do dose level 2 as we only had data on 2 patients and need an n>2 to do paired analyses.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 4 YU (Dose Level 1)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.375
Comments The reported p-value is representative of the changes in levels of sCD27 cytokines at dose level 1.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 40 YU (Dose Level 3)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.2036
Comments The reported p-value is representative of the changes in levels of sCD27 cytokines at dose level 3.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 80 YU (Dose Level 4)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.0742
Comments The reported p-value is representative of the changes in levels of sCD27 cytokines at dose level 4.
Method Wilcoxon test
Comments [Not Specified]
7.Secondary Outcome
Title Median Ratio of Soluble Cluster of Differentiation 27:40L (sCD27:sCD40L)
Hide Description Blood samples were collected and changes in serum levels of the ratio of soluble sCD27:sCD40L was assessed by enzyme-linked immunosorbent assay (ELISA). Significance of changes in soluble sCD27:sCD40L was determined by p value (Wilcoxon test) and the median and interquartile range of data.
Time Frame Pre (Baseline) and Day 85 after 6 vaccinations
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Due to insufficient samples at some time points in some patients, all participants were not analyzed in dose levels 2, 3 and 4; thus a statistical analysis was not performed.
Arm/Group Title 4 YU (Dose Level 1) 16 YU (Dose Level 2) 40 YU (Dose Level 3) 80 YU (Dose Level 4)
Hide Arm/Group Description:
Yeast-Brachyury vaccine will be administered subcutaneously at 4 sites on 7 visits, then monthly until patients meet off-treatment criteria.
Yeast-Brachyury vaccine will be administered subcutaneously at 4 sites on 7 visits, then monthly until patients meet off-treatment criteria.
Yeast-Brachyury vaccine will be administered subcutaneously at 4 sites on 7 visits, then monthly until patients meet off-treatment criteria.
Yeast-Brachyury vaccine will be administered subcutaneously at 4 sites on 7 visits, then monthly until patients meet off-treatment criteria.
Overall Number of Participants Analyzed 4 2 12 9
Median (Inter-Quartile Range)
Unit of Measure: Ratio
Median sCD27:sCD40L Pre
5.982
(5.71 to 11.67)
9.57
(7.88 to 11.26)
9.571
(7.67 to 19.89)
8.57
(6.93 to 10.62)
Median sCD27:sCD40L d85
6.428
(4.79 to 9.43)
8.294
(7.29 to 9.29)
10.47
(6.63 to 19.38)
8.257
(6.96 to 8.91)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 4 YU (Dose Level 1), 40 YU (Dose Level 3), 80 YU (Dose Level 4)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.1004
Comments The reported p-value is representative of the changes in levels of all ratio sCD27:sCD40AL cytokines at dose levels 1, 3, and 4. We could not do dose level 2 as we only had data on 2 patients and need an n>2 to do paired analyses.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 4 YU (Dose Level 1)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.625
Comments The reported p-value is representative of the changes in levels of ratio sCD27:sCD40L cytokines at dose level 1.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 40 YU (Dose Level 3)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.6772
Comments The reported p-value is representative of the changes in levels of ratio sCD27:sCD40L cytokines at dose level 3.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 80 YU (Dose Level 4)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.3008
Comments The reported p-value is representative of the changes in levels of ratio sCD27:sCD40L cytokines at dose level 4.
Method Wilcoxon test
Comments [Not Specified]
8.Secondary Outcome
Title Changes in Soluble Cluster of Differentiation 40L (sCD40L)
Hide Description Blood samples were collected and changes in serum levels of soluble sCD27 were assessed by enzyme-linked immunosorbent assay (ELISA). Significance of changes in soluble sCD40L was determined by p value (Wilcoxon test) and the median and interquartile range of data.
Time Frame Pre (Baseline) and Day 85 after 6 vaccinations
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Due to insufficient samples at some time points in some patients, all participants were not analyzed in dose levels 2, 3 and 4; thus a statistical analysis was not performed.
Arm/Group Title 4 YU (Dose Level 1) 16 YU (Dose Level 2) 40 YU (Dose Level 3) 80 YU (Dose Level 4)
Hide Arm/Group Description:
Yeast-Brachyury vaccine will be administered subcutaneously at 4 sites on 7 visits, then monthly until patients meet off-treatment criteria.
Yeast-Brachyury vaccine will be administered subcutaneously at 4 sites on 7 visits, then monthly until patients meet off-treatment criteria.
Yeast-Brachyury vaccine will be administered subcutaneously at 4 sites on 7 visits, then monthly until patients meet off-treatment criteria.
Yeast-Brachyury vaccine will be administered subcutaneously at 4 sites on 7 visits, then monthly until patients meet off-treatment criteria.
Overall Number of Participants Analyzed 4 2 12 9
Median (Inter-Quartile Range)
Unit of Measure: ng/ml
Median sCD40L Pre
15.3
(11.39 to 17.99)
10.24
(9.78 to 11.06)
9.648
(5.27 to 13.99)
14.72
(13.67 to 18.74)
Median sCD40L d85
15.23
(11.96 to 19.42)
11.14
(10.84 to 11.43)
9.854
(5.86 to 14.52)
18.57
(16.09 to 19.51)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 4 YU (Dose Level 1), 40 YU (Dose Level 3), 80 YU (Dose Level 4)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.0621
Comments The reported p-value is representative of the changes in levels of all sCD40L cytokines at dose levels 1, 3, and 4. We could not do dose level 2 as we only had data on 2 patients and need an n>2 to do paired analyses.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 4 YU (Dose Level 1)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.875
Comments The reported p-value is representative of the changes in levels of sCD40L cytokines at dose level 1.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 40 YU (Dose Level 3)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.2402
Comments The reported p-value is representative of the changes in levels of sCD40L cytokines at dose level 3.
Method Wilcoxon test
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 80 YU (Dose Level 4)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Significance was met if the unadjusted p-value was <0.05 and >1/2 of patients had a serum level change of >25%.
Statistical Test of Hypothesis P-Value 0.3008
Comments The reported p-value is representative of the changes in levels of sCD40L cytokines at dose level 4.
Method Wilcoxon test
Comments [Not Specified]
Time Frame 4 years and 25 days
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title 4 YU (Dose Level 1) 16 YU (Dose Level 2) 40 YU (Dose Level 3) 80 YU (Dose Level 4)
Hide Arm/Group Description Yeast-Brachyury vaccine will be administered subcutaneously at 4 sites on 7 visits, then monthly until patients meet off-treatment criteria. Yeast-Brachyury vaccine will be administered subcutaneously at 4 sites on 7 visits, then monthly until patients meet off-treatment criteria. Yeast-Brachyury vaccine will be administered subcutaneously at 4 sites on 7 visits, then monthly until patients meet off-treatment criteria. Yeast-Brachyury vaccine will be administered subcutaneously at 4 sites on 7 visits, then monthly until patients meet off-treatment criteria.
All-Cause Mortality
4 YU (Dose Level 1) 16 YU (Dose Level 2) 40 YU (Dose Level 3) 80 YU (Dose Level 4)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/4 (0.00%)      0/3 (0.00%)      0/16 (0.00%)      0/11 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
4 YU (Dose Level 1) 16 YU (Dose Level 2) 40 YU (Dose Level 3) 80 YU (Dose Level 4)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/4 (0.00%)      0/3 (0.00%)      5/16 (31.25%)      6/11 (54.55%)    
Cardiac disorders         
Aortic valve disease  1  0/4 (0.00%)  0 0/3 (0.00%)  0 1/16 (6.25%)  1 0/11 (0.00%)  0
Atrial fibrillation  1  0/4 (0.00%)  0 0/3 (0.00%)  0 1/16 (6.25%)  1 0/11 (0.00%)  0
Eye disorders         
Eye infection  1  0/4 (0.00%)  0 0/3 (0.00%)  0 0/16 (0.00%)  0 1/11 (9.09%)  1
Gastrointestinal disorders         
Abdominal pain  1  0/4 (0.00%)  0 0/3 (0.00%)  0 1/16 (6.25%)  1 0/11 (0.00%)  0
Small intestinal obstruction  1  0/4 (0.00%)  0 0/3 (0.00%)  0 3/16 (18.75%)  3 2/11 (18.18%)  2
General disorders         
Fatigue  1  0/4 (0.00%)  0 0/3 (0.00%)  0 0/16 (0.00%)  0 1/11 (9.09%)  1
Hepatobiliary disorders         
Cholecystitis  1  0/4 (0.00%)  0 0/3 (0.00%)  0 0/16 (0.00%)  0 1/11 (9.09%)  1
Infections and infestations         
Wound infection  1  0/4 (0.00%)  0 0/3 (0.00%)  0 1/16 (6.25%)  1 1/11 (9.09%)  1
Bone infection  1  0/4 (0.00%)  0 0/3 (0.00%)  0 0/16 (0.00%)  0 1/11 (9.09%)  1
Lung infection  1  0/4 (0.00%)  0 0/3 (0.00%)  0 0/16 (0.00%)  0 1/11 (9.09%)  2
Soft tissue infection  1  0/4 (0.00%)  0 0/3 (0.00%)  0 0/16 (0.00%)  0 1/11 (9.09%)  1
Metabolism and nutrition disorders         
Hyperglycemia  1  0/4 (0.00%)  0 0/3 (0.00%)  0 1/16 (6.25%)  1 0/11 (0.00%)  0
Musculoskeletal and connective tissue disorders         
Chest wall pain  1  0/4 (0.00%)  0 0/3 (0.00%)  0 1/16 (6.25%)  1 0/11 (0.00%)  0
Renal and urinary disorders         
Urinary tract obstruction  1  0/4 (0.00%)  0 0/3 (0.00%)  0 1/16 (6.25%)  1 0/11 (0.00%)  0
Urinary tract infection  1  0/4 (0.00%)  0 0/3 (0.00%)  0 0/16 (0.00%)  0 1/11 (9.09%)  1
Respiratory, thoracic and mediastinal disorders         
Atelectasis  1  0/4 (0.00%)  0 0/3 (0.00%)  0 0/16 (0.00%)  0 1/11 (9.09%)  1
Respiratory, thoracic and mediastinal disorders - Other, lung obstruction  1  0/4 (0.00%)  0 0/3 (0.00%)  0 0/16 (0.00%)  0 1/11 (9.09%)  1
Upper respiratory infection  1  0/4 (0.00%)  0 0/3 (0.00%)  0 0/16 (0.00%)  0 1/11 (9.09%)  1
Wheezing  1  0/4 (0.00%)  0 0/3 (0.00%)  0 0/16 (0.00%)  0 1/11 (9.09%)  1
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
4 YU (Dose Level 1) 16 YU (Dose Level 2) 40 YU (Dose Level 3) 80 YU (Dose Level 4)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/4 (100.00%)      3/3 (100.00%)      16/16 (100.00%)      10/11 (90.91%)    
Blood and lymphatic system disorders         
Anemia  1  0/4 (0.00%)  0 2/3 (66.67%)  3 11/16 (68.75%)  16 3/11 (27.27%)  7
Cardiac disorders         
Cardiac troponin I increased  1  0/4 (0.00%)  0 0/3 (0.00%)  0 1/16 (6.25%)  1 0/11 (0.00%)  0
Sinus bradycardia  1  0/4 (0.00%)  0 0/3 (0.00%)  0 1/16 (6.25%)  1 0/11 (0.00%)  0
Ear and labyrinth disorders         
Ear pain  1  0/4 (0.00%)  0 0/3 (0.00%)  0 1/16 (6.25%)  1 0/11 (0.00%)  0
Eye disorders         
Conjunctivitis  1  1/4 (25.00%)  1 0/3 (0.00%)  0 0/16 (0.00%)  0 0/11 (0.00%)  0
Cataract  1  0/4 (0.00%)  0 1/3 (33.33%)  1 0/16 (0.00%)  0 0/11 (0.00%)  0
Gastrointestinal disorders         
Diarrhea  1  1/4 (25.00%)  2 0/3 (0.00%)  0 0/16 (0.00%)  0 2/11 (18.18%)  2
Nausea  1  0/4 (0.00%)  0 1/3 (33.33%)  1 2/16 (12.50%)  2 2/11 (18.18%)  2
Abdominal pain  1  0/4 (0.00%)  0 0/3 (0.00%)  0 0/16 (0.00%)  0 1/11 (9.09%)  3
Ascites  1  0/4 (0.00%)  0 0/3 (0.00%)  0 1/16 (6.25%)  1 0/11 (0.00%)  0
Bloating  1  0/4 (0.00%)  0 0/3 (0.00%)  0 1/16 (6.25%)  1 0/11 (0.00%)  0
Constipation  1  0/4 (0.00%)  0 0/3 (0.00%)  0 1/16 (6.25%)  1 0/11 (0.00%)  0
Gastroesophageal reflux disease  1  0/4 (0.00%)  0 0/3 (0.00%)  0 1/16 (6.25%)  2 0/11 (0.00%)  0
Vomiting  1  0/4 (0.00%)  0 0/3 (0.00%)  0 1/16 (6.25%)  1 1/11 (9.09%)  1
Dyspepsia  1  0/4 (0.00%)  0 0/3 (0.00%)  0 0/16 (0.00%)  0 1/11 (9.09%)  1
Dysphagia  1  0/4 (0.00%)  0 0/3 (0.00%)  0 0/16 (0.00%)  0 1/11 (9.09%)  1
Gastrointestinal disorders - Other, poor appetite  1  0/4 (0.00%)  0 0/3 (0.00%)  0 0/16 (0.00%)  0 1/11 (9.09%)  1
Oral pain  1  0/4 (0.00%)  0 0/3 (0.00%)  0 0/16 (0.00%)  0 1/11 (9.09%)  1
General disorders         
Edema face  1  1/4 (25.00%)  1 0/3 (0.00%)  0 0/16 (0.00%)  0 0/11 (0.00%)  0
Edema limbs  1  1/4 (25.00%)  1 0/3 (0.00%)  0 0/16 (0.00%)  0 1/11 (9.09%)  1
Flu like symptoms  1  1/4 (25.00%)  1 1/3 (33.33%)  1 0/16 (0.00%)  0 1/11 (9.09%)  1
Injection site reaction  1  4/4 (100.00%)  7 1/3 (33.33%)  2 0/16 (0.00%)  0 9/11 (81.82%)  33
Pain  1  2/4 (50.00%)  3 0/3 (0.00%)  0 0/16 (0.00%)  0 3/11 (27.27%)  4
Fever  1  0/4 (0.00%)  0 1/3 (33.33%)  1 0/16 (0.00%)  0 2/11 (18.18%)  3
Chills  1  0/4 (0.00%)  0 0/3 (0.00%)  0 1/16 (6.25%)  1 0/11 (0.00%)  0
Fatigue  1  0/4 (0.00%)  0 0/3 (0.00%)  0 2/16 (12.50%)  3 4/11 (36.36%)  4
Fever  1  0/4 (0.00%)  0 0/3 (0.00%)  0 2/16 (12.50%)  3 0/11 (0.00%)  0
Gait disturbance  1  0/4 (0.00%)  0 0/3 (0.00%)  0 1/16 (6.25%)  1 0/11 (0.00%)  0
Infections and infestations         
Urinary tract infection  1  1/4 (25.00%)  1 0/3 (0.00%)  0 0/16 (0.00%)  0 0/11 (0.00%)  0
Infections and infestations - Other, herpes zoster  1  0/4 (0.00%)  0 0/3 (0.00%)  0 1/16 (6.25%)  1 0/11 (0.00%)  0
Rhinitis infective  1  0/4 (0.00%)  0 0/3 (0.00%)  0 2/16 (12.50%)  2 0/11 (0.00%)  0
Upper respiratory infection  1  0/4 (0.00%)  0 0/3 (0.00%)  0 1/16 (6.25%)  1 1/11 (9.09%)  1
Urinary tract infection  1  0/4 (0.00%)  0 0/3 (0.00%)  0 1/16 (6.25%)  1 0/11 (0.00%)  0
Wound infection  1  0/4 (0.00%)  0 0/3 (0.00%)  0 1/16 (6.25%)  1 1/11 (9.09%)  1
Eye infection  1  0/4 (0.00%)  0 0/3 (0.00%)  0 0/16 (0.00%)  0 1/11 (9.09%)  1
Infections and infestations - Other, nephrostomy tube site  1  0/4 (0.00%)  0 0/3 (0.00%)  0 0/16 (0.00%)  0 1/11 (9.09%)  1
Lung infection  1  0/4 (0.00%)  0 0/3 (0.00%)  0 0/16 (0.00%)  0 1/11 (9.09%)  2
Mucosal infection  1  0/4 (0.00%)  0 0/3 (0.00%)  0 0/16 (0.00%)  0 1/11 (9.09%)  1
Skin infection  1  0/4 (0.00%)  0 0/3 (0.00%)  0 0/16 (0.00%)  0 1/11 (9.09%)  1
Soft tissue infection  1  0/4 (0.00%)  0 0/3 (0.00%)  0 0/16 (0.00%)  0 1/11 (9.09%)  1
Injury, poisoning and procedural complications         
Fall  1  1/4 (25.00%)  1 0/3 (0.00%)  0 0/16 (0.00%)  0 1/11 (9.09%)  1
Fracture  1  0/4 (0.00%)  0 0/3 (0.00%)  0 0/16 (0.00%)  0 2/11 (18.18%)  2
Investigations         
Alanine aminotransferase increased  1  1/4 (25.00%)  1 0/3 (0.00%)  0 3/16 (18.75%)  4 1/11 (9.09%)  1
Alkaline phosphatase increased  1  1/4 (25.00%)  2 0/3 (0.00%)  0 4/16 (25.00%)  4 3/11 (27.27%)  3
Lymphocyte count decreased  1  3/4 (75.00%)  4 1/3 (33.33%)  1 0/16 (0.00%)  0 0/11 (0.00%)  0
Platelet count decreased  1  1/4 (25.00%)  2 1/3 (33.33%)  1 0/16 (0.00%)  0 0/11 (0.00%)  0
Aspartate aminotransferase increased  1  0/4 (0.00%)  0 1/3 (33.33%)  1 2/16 (12.50%)  2 2/11 (18.18%)  2
Weight loss  1  0/4 (0.00%)  0 1/3 (33.33%)  1 1/16 (6.25%)  2 2/11 (18.18%)  2
CD4 lymphocytes decreased  1  0/4 (0.00%)  0 0/3 (0.00%)  0 1/16 (6.25%)  1 0/11 (0.00%)  0
Creatinine increased  1  0/4 (0.00%)  0 0/3 (0.00%)  0 2/16 (12.50%)  3 3/11 (27.27%)  6
Neutrophil count decreased  1  0/4 (0.00%)  0 0/3 (0.00%)  0 2/16 (12.50%)  2 1/11 (9.09%)  1
White blood cell decreased  1  0/4 (0.00%)  0 0/3 (0.00%)  0 5/16 (31.25%)  5 1/11 (9.09%)  1
Metabolism and nutrition disorders         
Hypoalbuminemia  1  2/4 (50.00%)  6 0/3 (0.00%)  0 0/16 (0.00%)  0 0/11 (0.00%)  0
Anorexia  1  0/4 (0.00%)  0 1/3 (33.33%)  1 1/16 (6.25%)  1 1/11 (9.09%)  1
Hyperglycemia  1  0/4 (0.00%)  0 1/3 (33.33%)  1 0/16 (0.00%)  0 5/11 (45.45%)  9
Hyperkalemia  1  0/4 (0.00%)  0 1/3 (33.33%)  1 0/16 (0.00%)  0 0/11 (0.00%)  0
Hypermagnesemia  1  0/4 (0.00%)  0 1/3 (33.33%)  1 1/16 (6.25%)  1 0/11 (0.00%)  0
Hypercalcemia  1  0/4 (0.00%)  0 0/3 (0.00%)  0 1/16 (6.25%)  1 2/11 (18.18%)  2
Hypernatremia  1  0/4 (0.00%)  0 0/3 (0.00%)  0 1/16 (6.25%)  1 2/11 (18.18%)  2
Hypocalcemia  1  0/4 (0.00%)  0 0/3 (0.00%)  0 1/16 (6.25%)  1 1/11 (9.09%)  1
Hypoglycemia  1  0/4 (0.00%)  0 0/3 (0.00%)  0 2/16 (12.50%)  2 2/11 (18.18%)  2
Hypokalemia  1  0/4 (0.00%)  0 0/3 (0.00%)  0 1/16 (6.25%)  1 1/11 (9.09%)  1
Hypomagnesemia  1  0/4 (0.00%)  0 0/3 (0.00%)  0 1/16 (6.25%)  1 0/11 (0.00%)  0
Hyponatremia  1  0/4 (0.00%)  0 0/3 (0.00%)  0 1/16 (6.25%)  1 3/11 (27.27%)  3
Hypophosphatemia  1  0/4 (0.00%)  0 0/3 (0.00%)  0 5/16 (31.25%)  6 1/11 (9.09%)  2
Metabolism and nutrition disorders - Other, hemoglobinuria  1  0/4 (0.00%)  0 0/3 (0.00%)  0 1/16 (6.25%)  1 0/11 (0.00%)  0
Musculoskeletal and connective tissue disorders         
Pain in extremity  1  1/4 (25.00%)  1 0/3 (0.00%)  0 3/16 (18.75%)  3 2/11 (18.18%)  2
Buttock pain  1  0/4 (0.00%)  0 0/3 (0.00%)  0 1/16 (6.25%)  1 0/11 (0.00%)  0
Chest wall pain  1  0/4 (0.00%)  0 0/3 (0.00%)  0 1/16 (6.25%)  2 0/11 (0.00%)  0
Joint effusion  1  0/4 (0.00%)  0 0/3 (0.00%)  0 1/16 (6.25%)  1 0/11 (0.00%)  0
Muscle weakness left-sided  1  0/4 (0.00%)  0 0/3 (0.00%)  0 1/16 (6.25%)  1 0/11 (0.00%)  0
Muscle weakness upper limb  1  0/4 (0.00%)  0 0/3 (0.00%)  0 1/16 (6.25%)  1 0/11 (0.00%)  0
Myalgia  1  0/4 (0.00%)  0 0/3 (0.00%)  0 1/16 (6.25%)  1 1/11 (9.09%)  1
Back pain  1  0/4 (0.00%)  0 0/3 (0.00%)  0 0/16 (0.00%)  0 1/11 (9.09%)  1
Flank pain  1  0/4 (0.00%)  0 0/3 (0.00%)  0 0/16 (0.00%)  0 1/11 (9.09%)  1
Generalized muscle weakness  1  0/4 (0.00%)  0 0/3 (0.00%)  0 0/16 (0.00%)  0 1/11 (9.09%)  1
Muscle weakness right-sided  1  0/4 (0.00%)  0 0/3 (0.00%)  0 0/16 (0.00%)  0 1/11 (9.09%)  1
Musculoskeletal and connective tissue disorder-Other, R knee swelling  1 [1]  0/4 (0.00%)  0 0/3 (0.00%)  0 0/16 (0.00%)  0 1/11 (9.09%)  1
Non-cardiac chest pain  1  0/4 (0.00%)  0 0/3 (0.00%)  0 0/16 (0.00%)  0 1/11 (9.09%)  1
Nervous system disorders         
Dizziness  1  0/4 (0.00%)  0 0/3 (0.00%)  0 1/16 (6.25%)  1 0/11 (0.00%)  0
Headache  1  0/4 (0.00%)  0 0/3 (0.00%)  0 3/16 (18.75%)  3 0/11 (0.00%)  0
Nervous system disorders - Other, lightheadedness  1  0/4 (0.00%)  0 0/3 (0.00%)  0 1/16 (6.25%)  2 0/11 (0.00%)  0
Paresthesia  1  0/4 (0.00%)  0 0/3 (0.00%)  0 1/16 (6.25%)  1 0/11 (0.00%)  0
Peripheral motor neuropathy  1  0/4 (0.00%)  0 0/3 (0.00%)  0 1/16 (6.25%)  1 0/11 (0.00%)  0
Peripheral sensory neuropathy  1  0/4 (0.00%)  0 0/3 (0.00%)  0 1/16 (6.25%)  1 1/11 (9.09%)  1
Psychiatric disorders         
Anxiety  1  0/4 (0.00%)  0 0/3 (0.00%)  0 0/16 (0.00%)  0 1/11 (9.09%)  1
Renal and urinary disorders         
Cystitis noninfective  1  1/4 (25.00%)  1 0/3 (0.00%)  0 0/16 (0.00%)  0 0/11 (0.00%)  0
Urinary urgency  1  1/4 (25.00%)  1