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Trial of Otelixizumab for Adolescents and Adults With Newly Diagnosed Type 1 Diabetes Mellitus (Autoimmune): DEFEND-2 (DEFEND-2)

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ClinicalTrials.gov Identifier: NCT01123083
Recruitment Status : Completed
First Posted : May 14, 2010
Results First Posted : September 15, 2017
Last Update Posted : September 15, 2017
Sponsor:
Collaborator:
Juvenile Diabetes Research Foundation
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Diabetes Mellitus, Type 1
Interventions Biological: Otelixizumab
Biological: Placebo
Enrollment 179
Recruitment Details This study was conducted across 73 centers in 10 countries (Belgium, Canada, Germany, Denmark, Spain, Finland, United Kingdom, Italy, Sweden, and United States of America) from 17 May 2010 to 09 March 2012.
Pre-assignment Details A total of 179 participants (125 adults and 54 adolescents) were randomized in this study and included in safety and intent-to-treat (ITT) population.
Arm/Group Title Placebo Otelixizumab
Hide Arm/Group Description Eligible participants received Placebo matching otelixizumab 3.1 milligrams (mg) as intravenous (IV) infusion, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per day over 8 consecutive days. Eligible participants received otelixizumab 3.1 mg as IV infusion, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per day over 8 consecutive days.
Period Title: Overall Study
Started 61 118
Completed 50 103
Not Completed 11 15
Reason Not Completed
Investigator recommendation             1             1
Administrative reasons             0             4
Lost to Follow-up             2             6
Adverse Event             1             0
Withdrew for another reason not covered             0             1
Participant/legal representative request             7             3
Arm/Group Title Placebo Otelixizumab Total
Hide Arm/Group Description Eligible participants received Placebo matching otelixizumab 3.1 mg as IV infusion, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per day over 8 consecutive days. Eligible participants received otelixizumab 3.1 mg as IV infusion, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per day over 8 consecutive days. Total of all reporting groups
Overall Number of Baseline Participants 61 118 179
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 61 participants 118 participants 179 participants
22.5  (8.22) 23.6  (8.34) 23.2  (8.29)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 61 participants 118 participants 179 participants
Female
24
  39.3%
50
  42.4%
74
  41.3%
Male
37
  60.7%
68
  57.6%
105
  58.7%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 61 participants 118 participants 179 participants
American Indian or Alaska Native
1
   1.6%
1
   0.8%
2
   1.1%
Asian
1
   1.6%
2
   1.7%
3
   1.7%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
1
   1.6%
2
   1.7%
3
   1.7%
White
54
  88.5%
111
  94.1%
165
  92.2%
More than one race
4
   6.6%
2
   1.7%
6
   3.4%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Change From Baseline in 2 Hour Mixed Meal-stimulated C-peptide Area Under Curve (AUC) (Normalized for 120-minute Time Interval) at Month 12
Hide Description C-peptide is a protein that shows how much insulin the body is producing. For 3 days before the mixed meal tolerance test participants were asked to eat a balanced diet. The test was performed only when the finger-stick blood glucose level was above 70 mg per deciliter (mg/dL) and no higher than 200 mg/dL. Mixed meal-stimulated C-peptide AUC was the area under the C-peptide/time curve from time 0 to 120-minutes, calculated using the trapezoidal rule. This AUC was normalized for time interval by dividing it by 120-minutes (the number of minutes over which it was determined), and was adjusted by inclusion of Baseline C-peptide AUC as a covariate in the analysis. Baseline was defined at Day 1. Change from Baseline was calculated by subtracting the value at Month 12 from the Baseline value.
Time Frame Baseline (Day 1) and Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population consisted of all participants who were randomized and received any part of at least 1 infusion of study drug. Only those participants available at the indicated time points were analyzed.
Arm/Group Title Placebo Otelixizumab
Hide Arm/Group Description:
Eligible participants received Placebo matching otelixizumab 3.1 mg as IV infusion, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per day over 8 consecutive days.
Eligible participants received otelixizumab 3.1 mg as IV infusion, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per day over 8 consecutive days.
Overall Number of Participants Analyzed 45 96
Least Squares Mean (Standard Error)
Unit of Measure: nanomoles per liter
-0.14  (0.036) -0.23  (0.026)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Otelixizumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.051
Comments [Not Specified]
Method Repeated Measures Mixed Effects Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.09
Confidence Interval (2-Sided) 95%
-0.17 to 0.00
Estimation Comments Estimated treatment group difference, adjusted for age, region and Baseline C-peptide AUC. Confidence Interval, not adjusted for multiple comparisons.
2.Secondary Outcome
Title Change From Baseline in 2 Hour Mixed Meal-stimulated C-peptide AUC (Normalized for 120-minute Time Interval) at Week 12 and 6 Months
Hide Description C-peptide is a protein that shows how much insulin the body is producing. For 3 days before the mixed meal tolerance test participants were asked to eat a balanced diet. The test was performed only when the finger-stick blood glucose level was above 70 mg/dL and no higher than 200 mg/dL. Mixed meal-stimulated C-peptide AUC was the area under the C-peptide/time curve from time 0 to 120-minutes, calculated using the trapezoidal rule. This AUC was normalized for time interval by dividing it by 120-minutes (the number of minutes over which it was determined), and was adjusted by inclusion of Baseline C-peptide AUC as a covariate in the analysis. Baseline was defined at Day 1. Change from Baseline was calculated by subtracting the post Baseline value from the Baseline value.
Time Frame Baseline (Day 1) and Week 12, Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Only those participants available at the indicated time points were analyzed.
Arm/Group Title Placebo Otelixizumab
Hide Arm/Group Description:
Eligible participants received Placebo matching otelixizumab 3.1 mg as IV infusion, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per day over 8 consecutive days.
Eligible participants received otelixizumab 3.1 mg as IV infusion, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per day over 8 consecutive days.
Overall Number of Participants Analyzed 61 118
Least Squares Mean (Standard Error)
Unit of Measure: nanomoles per liter
Week 12 Number Analyzed 55 participants 105 participants
0.05  (0.031) -0.05  (0.023)
Month 6 Number Analyzed 50 participants 99 participants
-0.04  (0.037) -0.10  (0.027)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Otelixizumab
Comments Week 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.022
Comments [Not Specified]
Method Repeated Measures Mixed Effects Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.10
Confidence Interval (2-Sided) 95%
-0.18 to -0.02
Estimation Comments Estimated treatment group difference, adjusted for age, region and Baseline C-peptide AUC. Confidence Interval, not adjusted for multiple comparisons.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Otelixizumab
Comments Month 6
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.191
Comments [Not Specified]
Method Repeated Measures Mixed Effects Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.06
Confidence Interval (2-Sided) 95%
-0.15 to 0.03
Estimation Comments Estimated treatment group difference, adjusted for age, region and Baseline C-peptide AUC. Confidence Interval, not adjusted for multiple comparisons.
3.Secondary Outcome
Title Change From Baseline in Stimulated C-Peptide Mean AUC at Week 12, Month 6, 12 and 18
Hide Description C-peptide is a protein that shows how much insulin the body is producing. For 3 days before the mixed meal tolerance test participants were asked to eat a balanced diet. The test was performed only when the finger-stick blood glucose level was above 70 mg/dL and no higher than 200 mg/dL. Mixed meal-stimulated C-peptide AUC was the area under the C-peptide/time curve from time 0 to 120-minutes, calculated using the trapezoidal rule. This AUC was normalized for time interval by dividing it by 120-minutes (the number of minutes over which it was determined), and was adjusted by inclusion of Baseline C-peptide AUC as a covariate in the analysis. Baseline was defined at Day 1. Change from Baseline was calculated by subtracting the post Baseline value from the Baseline value.
Time Frame Baseline (Day 1) and Week 12, Month 6, 12, 18
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Only those participants available at the indicated time points were analyzed.
Arm/Group Title Placebo Otelixizumab
Hide Arm/Group Description:
Eligible participants received Placebo matching otelixizumab 3.1 mg as IV infusion, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per day over 8 consecutive days.
Eligible participants received otelixizumab 3.1 mg as IV infusion, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per day over 8 consecutive days.
Overall Number of Participants Analyzed 61 118
Mean (Standard Deviation)
Unit of Measure: nanomoles per liter
Week 12 Number Analyzed 55 participants 105 participants
0.0519  (0.24430) -0.0472  (0.23394)
Month 6 Number Analyzed 50 participants 99 participants
-0.0455  (0.23802) -0.0945  (0.29151)
Month 12 Number Analyzed 45 participants 96 participants
-0.1236  (0.24362) -0.2331  (0.30537)
Month 18 Number Analyzed 2 participants 4 participants
-0.4125  (0.17059) 0.0502  (0.25597)
4.Secondary Outcome
Title Number of Participants With Responder Status
Hide Description A participant was considered a responder when, at the given time point, the participant had: glycosylated hemoglobin (HbA1c) less than or equal to 6.5 percent and mean daily insulin use less than 0.5 international unit per kilogram per day (IU/kg/day) over 7 consecutive days during the 2 weeks preceding the visit.
Time Frame Month 3, 6 and 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Only those participants available at the indicated time points were analyzed.
Arm/Group Title Placebo Otelixizumab
Hide Arm/Group Description:
Eligible participants received Placebo matching otelixizumab 3.1 mg as IV infusion, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per day over 8 consecutive days.
Eligible participants received otelixizumab 3.1 mg as IV infusion, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per day over 8 consecutive days.
Overall Number of Participants Analyzed 61 118
Measure Type: Count of Participants
Unit of Measure: Participants
Week 12 Number Analyzed 41 participants 68 participants
19
  46.3%
42
  61.8%
Month 6 Number Analyzed 35 participants 61 participants
11
  31.4%
26
  42.6%
Month 12 Number Analyzed 27 participants 54 participants
10
  37.0%
23
  42.6%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Otelixizumab
Comments Week 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.912
Comments [Not Specified]
Method GEE Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.29
Confidence Interval (2-Sided) 95%
0.50 to 3.37
Estimation Comments Estimated treatment group difference, adjusted for age, region and Baseline HbA1c/Insulin Use Response. Confidence Interval, not adjusted for multiple comparisons.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Otelixizumab
Comments Month 6
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.912
Comments [Not Specified]
Method GEE Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.95
Confidence Interval (2-Sided) 95%
0.37 to 2.42
Estimation Comments Estimated treatment group difference, adjusted for age, region and Baseline HbA1c/Insulin Use Response. Confidence Interval, not adjusted for multiple comparisons.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Otelixizumab
Comments Month 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.412
Comments [Not Specified]
Method GEE Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.56
Confidence Interval (2-Sided) 95%
0.54 to 4.52
Estimation Comments Estimated treatment group difference, adjusted for age, region and Baseline HbA1c/Insulin Use Response. Confidence Interval, not adjusted for multiple comparisons.
5.Secondary Outcome
Title Change From Baseline in Mean Daily Insulin Use Over 7 Consecutive Days During the 2 Weeks Prior to the Assessment
Hide Description Mean daily insulin use over 7 consecutive days during the 2 weeks preceding each key visit was calculated as the mean of the values of amount of insulin used per day on each of the 7 consecutive days. Baseline was defined at Day 1. Change from Baseline was calculated by subtracting the post Baseline value from the Baseline value.
Time Frame Baseline (Day 1) and Month 3, 6, 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Only those participants available at the indicated time points were analyzed.
Arm/Group Title Placebo Otelixizumab
Hide Arm/Group Description:
Eligible participants received Placebo matching otelixizumab 3.1 mg as IV infusion, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per day over 8 consecutive days.
Eligible participants received otelixizumab 3.1 mg as IV infusion, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per day over 8 consecutive days.
Overall Number of Participants Analyzed 61 118
Least Squares Mean (Standard Error)
Unit of Measure: International unit per kilogram (IU/kg)
Week 12 Number Analyzed 35 participants 55 participants
-0.04  (0.020) -0.08  (0.016)
Month 6 Number Analyzed 33 participants 55 participants
0.01  (0.027) -0.04  (0.021)
Month 12 Number Analyzed 26 participants 45 participants
0.01  (0.036) 0.05  (0.028)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Otelixizumab
Comments Week 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.210
Comments [Not Specified]
Method Repeated Measures Mixed Effects Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.03
Confidence Interval (2-Sided) 95%
-0.08 to 0.02
Estimation Comments Estimated treatment group difference, adjusted for age, region and Baseline Mean Daily Insulin Use. Confidence Interval, not adjusted for multiple comparisons.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Otelixizumab
Comments Month 6
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.210
Comments [Not Specified]
Method Repeated Measures Mixed Effects Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.04
Confidence Interval (2-Sided) 95%
-0.11 to 0.02
Estimation Comments Estimated treatment group difference, adjusted for age, region and Baseline Mean Daily Insulin Use. Confidence Interval, not adjusted for multiple comparisons.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Otelixizumab
Comments Month 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.402
Comments [Not Specified]
Method Repeated Measures Mixed Effects Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.04
Confidence Interval (2-Sided) 95%
-0.05 to 0.13
Estimation Comments Estimated treatment group difference, adjusted for age, region and Baseline Mean Daily Insulin Use. Confidence Interval, not adjusted for multiple comparisons.
6.Secondary Outcome
Title Change From Baseline in HbA1c Levels Over 7 Consecutive Days During the 2 Weeks Prior to the Assessment
Hide Description HbA1c level was recorded at Baseline, Month 3, 6 and 12. Baseline was defined at Day 1. Change from Baseline was calculated by subtracting the post Baseline value from the Baseline value.
Time Frame Baseline (Day 1) and Month 3, 6, 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Only those participants available at the indicated time points were analyzed.
Arm/Group Title Placebo Otelixizumab
Hide Arm/Group Description:
Eligible participants received Placebo matching otelixizumab 3.1 mg as IV infusion, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per day over 8 consecutive days.
Eligible participants received otelixizumab 3.1 mg as IV infusion, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per day over 8 consecutive days.
Overall Number of Participants Analyzed 61 118
Least Squares Mean (Standard Error)
Unit of Measure: Percentage of HbA1c
Week 12 Number Analyzed 58 participants 109 participants
-0.82  (0.140) -1.01  (0.101)
Month 6 Number Analyzed 54 participants 94 participants
-0.65  (0.185) -0.65  (0.134)
Month 12 Number Analyzed 48 participants 99 participants
-0.61  (0.188) -0.47  (0.133)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Otelixizumab
Comments Week 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.582
Comments [Not Specified]
Method Repeated Measures Mixed Effects Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.18
Confidence Interval (2-Sided) 95%
-0.52 to 0.16
Estimation Comments Estimated treatment group difference, adjusted for age, region and baseline HbA1c. Confidence Interval, not adjusted for multiple comparisons.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Otelixizumab
Comments Month 6
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.987
Comments [Not Specified]
Method Repeated Measures Mixed Effects Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.00
Confidence Interval (2-Sided) 95%
-0.46 to 0.45
Estimation Comments Estimated treatment group difference, adjusted for age, region and baseline HbA1c. Confidence Interval, not adjusted for multiple comparisons.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Otelixizumab
Comments Month 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.572
Comments [Not Specified]
Method Repeated Measures Mixed Effects Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.13
Confidence Interval (2-Sided) 95%
-0.33 to 0.59
Estimation Comments Estimated treatment group difference, adjusted for age, region and baseline HbA1c. Confidence Interval, not adjusted for multiple comparisons.
7.Secondary Outcome
Title Average Number of Severe Hypoglycemic Events and Documented Symptomatic Hypoglycemic Events From Baseline to Month 12
Hide Description Severe hypoglycemia was considered as an event that required assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. These episodes may be associated with sufficient neuroglycopenia to induce seizure or coma. Plasma glucose measurements may not be available during such an event, but neurological recovery attributable to the restoration of plasma glucose to normal is considered sufficient evidence that the event was induced by a low plasma glucose concentration. Documented symptomatic hypoglycemia was considered as an event during which typical symptoms of hypoglycemia are accompanied by a measured plasma glucose concentration less than or equal to 70 mg/dL and it was collected in (1) eCRF using two forms – for single event and for mutiple events, and (2) the IVRS system. The numbers of participant-reported hypoglycemic events per participant of severe hypoglycemia and documented symptomatic hypoglycemia have been reported.
Time Frame Baseline (Day 1) and Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Placebo Otelixizumab
Hide Arm/Group Description:
Eligible participants received Placebo matching otelixizumab 3.1 mg as IV infusion, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per day over 8 consecutive days.
Eligible participants received otelixizumab 3.1 mg as IV infusion, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per day over 8 consecutive days.
Overall Number of Participants Analyzed 61 118
Measure Type: Number
Unit of Measure: Events
Severe hypoglycemia 33 11
Documented symptomatic hypoglycemia from IVRS 429 690
Documented symptomatic hypoglycemia from eCRF 822 1300
8.Secondary Outcome
Title Percentage of Participants With Change From Baseline in Severe Hypoglycemic Events and Documented Symptomatic Hypoglycemic Events at Month 12
Hide Description Severe hypoglycemia was considered as an event that required assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. These episodes may be associated with sufficient neuroglycopenia to induce seizure or coma. Plasma glucose measurements may not be available during such an event, but neurological recovery attributable to the restoration of plasma glucose to normal is considered sufficient evidence that the event was induced by a low plasma glucose concentration. Documented symptomatic hypoglycemia was considered as an event during which typical symptoms of hypoglycemia are accompanied by a measured plasma glucose concentration less than or equal to 70 mg/dL and it was collected in (1) eCRF using two forms – for single event and for mutiple events, and (2) the IVRS system. The percentage of participant with incidence of severe hypoglycemia and documented symptomatic hypoglycemia have been reported.
Time Frame Baseline (Day 1) and Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Placebo Otelixizumab
Hide Arm/Group Description:
Eligible participants received Placebo matching otelixizumab 3.1 mg as IV infusion, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per day over 8 consecutive days.
Eligible participants received otelixizumab 3.1 mg as IV infusion, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per day over 8 consecutive days.
Overall Number of Participants Analyzed 61 118
Measure Type: Number
Unit of Measure: Percentage of participants
Severe hypoglycemia 11.5 5.9
Documented symptomatic hypoglycemia from IVRS 36.1 28.8
Documented symptomatic hypoglycemia from eCRF 45.9 43.2
9.Secondary Outcome
Title Composite Rank Sum: HbA1c and Exogenous Insulin Use at 6 and 12 Months
Hide Description O'Brien mean rank analyses was performed on a two-part composite of the Baseline-adjusted HbA1c level and the Baseline-adjusted mean total daily insulin use per kg body weight in the otelixizumab group compared with the placebo group at Months 6 and 12. Baseline adjustment was used to reduce the potential impact of imbalances in Baseline levels between treatment groups on the treatment comparisons at later time points. For the O'Brien mean rank analysis at a particular time point, adjusted HbA1c values (for both treatment groups together) and adjusted mean daily insulin use values was ranked from smallest to largest. For each participant, the HbA1c and insulin use ranks were added together, producing a composite rank. A treatment comparison test was then performed on the composite ranks. If otelixizumab treatment was effective on this composite endpoint, then the mean of the ranks sum in the otelixizumab group was smaller than the mean of the ranks sum in the placebo group.
Time Frame Month 6 and 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Only those participants available at the indicated time points were analyzed.
Arm/Group Title Placebo Otelixizumab
Hide Arm/Group Description:
Eligible participants received Placebo matching otelixizumab 3.1 mg as IV infusion, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per day over 8 consecutive days.
Eligible participants received otelixizumab 3.1 mg as IV infusion, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per day over 8 consecutive days.
Overall Number of Participants Analyzed 61 118
Mean (Standard Deviation)
Unit of Measure: Rank
Month 6 Number Analyzed 28 participants 48 participants
119  (48.4) 110  (49.8)
Month 12 Number Analyzed 23 participants 45 participants
96  (51.2) 110  (55.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Otelixizumab
Comments Month 6
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.452
Comments [Not Specified]
Method Hochberg-adjusted p-value
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Otelixizumab
Comments Month 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.452
Comments [Not Specified]
Method Hochberg-adjusted p-value
Comments [Not Specified]
10.Secondary Outcome
Title Composite Rank Sum: C-Peptide AUC, HbA1c and Exogenous Insulin Use at 6 and 12 Months
Hide Description O'Brien analyses was performed on a three-part composite of HbA1c level, C-peptide AUC, and mean daily insulin use in the otelixizumab group compared with the placebo group at Months 6 and 12. The three variables was adjusted for Baseline values. Baseline adjustment was used to reduce the potential impact of imbalances in Baseline levels between treatment groups on the treatment comparisons at later time points. HbA1c and insulin use was ranked from smallest to largest, and C-peptide AUC was ranked from largest to smallest. If otelixizumab treatment was effective on the composite endpoint, then the mean of the ranks sum in the otelixizumab group was smaller than the mean of the ranks sum in the placebo group.
Time Frame Month 6 and 12
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Only those participants available at the indicated time points were analyzed.
Arm/Group Title Placebo Otelixizumab
Hide Arm/Group Description:
Eligible participants received Placebo matching otelixizumab 3.1 mg as IV infusion, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per day over 8 consecutive days.
Eligible participants received otelixizumab 3.1 mg as IV infusion, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per day over 8 consecutive days.
Overall Number of Participants Analyzed 61 118
Mean (Standard Deviation)
Unit of Measure: Rank
Month 6 Number Analyzed 26 participants 48 participants
206  (48.6) 186  (41.6)
Month 12 Number Analyzed 23 participants 42 participants
180  (42.5) 170  (46.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Otelixizumab
Comments Month 6
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.123
Comments [Not Specified]
Method Hochberg-adjusted p-value
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Otelixizumab
Comments Month 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.373
Comments [Not Specified]
Method Hochberg-adjusted p-value
Comments [Not Specified]
Time Frame Adverse events (AEs) and serious adverse events (SAEs) were collected from dosing Days 1 to 8 and until study withdrawal.
Adverse Event Reporting Description Safety population consisted of all participants for whom there was evidence that they received any part of at least 1 infusion of study drug.
 
Arm/Group Title Placebo Otelixizumab
Hide Arm/Group Description Eligible participants received Placebo matching otelixizumab 3.1 mg as IV infusion, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per day over 8 consecutive days. Eligible participants received otelixizumab 3.1 mg as IV infusion, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per day over 8 consecutive days.
All-Cause Mortality
Placebo Otelixizumab
Affected / at Risk (%) Affected / at Risk (%)
Total   0/61 (0.00%)   0/118 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Otelixizumab
Affected / at Risk (%) Affected / at Risk (%)
Total   4/61 (6.56%)   11/118 (9.32%) 
Congenital, familial and genetic disorders     
Atrial septal defect  1  1/61 (1.64%)  0/118 (0.00%) 
Gastrointestinal disorders     
Vomiting  1  0/61 (0.00%)  1/118 (0.85%) 
General disorders     
Malaise  1  0/61 (0.00%)  1/118 (0.85%) 
Immune system disorders     
Cytokine release syndrome  1  0/61 (0.00%)  2/118 (1.69%) 
Injury, poisoning and procedural complications     
Overdose  1  1/61 (1.64%)  0/118 (0.00%) 
Metabolism and nutrition disorders     
Hyperglycaemia  1  1/61 (1.64%)  1/118 (0.85%) 
Diabetic ketoacidosis  1  0/61 (0.00%)  1/118 (0.85%) 
Hypoglycaemia  1  0/61 (0.00%)  1/118 (0.85%) 
Musculoskeletal and connective tissue disorders     
Scoliosis  1  0/61 (0.00%)  1/118 (0.85%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Malignant melanoma in situ  1  0/61 (0.00%)  1/118 (0.85%) 
Thyroid cancer  1  0/61 (0.00%)  1/118 (0.85%) 
Nervous system disorders     
Convulsion  1  0/61 (0.00%)  1/118 (0.85%) 
Headache  1  0/61 (0.00%)  1/118 (0.85%) 
Loss of consciousness  1  0/61 (0.00%)  1/118 (0.85%) 
Pregnancy, puerperium and perinatal conditions     
Pregnancy induced hypertension  1  0/61 (0.00%)  1/118 (0.85%) 
Psychiatric disorders     
Major depression  1  1/61 (1.64%)  0/118 (0.00%) 
Suicidal ideation  1  1/61 (1.64%)  0/118 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  1  0/61 (0.00%)  1/118 (0.85%) 
Skin and subcutaneous tissue disorders     
Urticaria  1  0/61 (0.00%)  1/118 (0.85%) 
1
Term from vocabulary, MedDRA 11.1
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 5%
Placebo Otelixizumab
Affected / at Risk (%) Affected / at Risk (%)
Total   50/61 (81.97%)   108/118 (91.53%) 
Blood and lymphatic system disorders     
Lymphadenopathy  1  9/61 (14.75%)  8/118 (6.78%) 
Gastrointestinal disorders     
Nausea  1  16/61 (26.23%)  38/118 (32.20%) 
Vomiting  1  2/61 (3.28%)  19/118 (16.10%) 
Abdominal pain  1  5/61 (8.20%)  11/118 (9.32%) 
Diarrhoea  1  1/61 (1.64%)  11/118 (9.32%) 
Abdominal pain upper  1  1/61 (1.64%)  6/118 (5.08%) 
General disorders     
Fatigue  1  11/61 (18.03%)  28/118 (23.73%) 
Pyrexia  1  2/61 (3.28%)  21/118 (17.80%) 
Chills  1  3/61 (4.92%)  16/118 (13.56%) 
Malaise  1  4/61 (6.56%)  4/118 (3.39%) 
Infusion site erythema  1  0/61 (0.00%)  6/118 (5.08%) 
Infections and infestations     
Nasopharyngitis  1  15/61 (24.59%)  37/118 (31.36%) 
Upper respiratory tract infection  1  16/61 (26.23%)  9/118 (7.63%) 
Sinusitis  1  7/61 (11.48%)  3/118 (2.54%) 
Influenza  1  0/61 (0.00%)  9/118 (7.63%) 
Pharyngitis streptococcal  1  0/61 (0.00%)  6/118 (5.08%) 
Urinary tract infection  1  0/61 (0.00%)  6/118 (5.08%) 
Metabolism and nutrition disorders     
Hypoglycaemia  1  6/61 (9.84%)  12/118 (10.17%) 
Musculoskeletal and connective tissue disorders     
Myalgia  1  4/61 (6.56%)  11/118 (9.32%) 
Back pain  1  1/61 (1.64%)  12/118 (10.17%) 
Arthralgia  1  2/61 (3.28%)  7/118 (5.93%) 
Musculoskeletal pain  1  2/61 (3.28%)  7/118 (5.93%) 
Neck pain  1  0/61 (0.00%)  6/118 (5.08%) 
Pain in extremity  1  0/61 (0.00%)  6/118 (5.08%) 
Nervous system disorders     
Headache  1  34/61 (55.74%)  92/118 (77.97%) 
Dizziness  1  4/61 (6.56%)  12/118 (10.17%) 
Respiratory, thoracic and mediastinal disorders     
Oropharyngeal pain  1  7/61 (11.48%)  16/118 (13.56%) 
Cough  1  4/61 (6.56%)  9/118 (7.63%) 
Nasal congestion  1  1/61 (1.64%)  7/118 (5.93%) 
1
Term from vocabulary, MedDRA 11.1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Results Point of Contact
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01123083     History of Changes
Other Study ID Numbers: 115494
TRX4018 ( Other Identifier: Tolerx )
First Submitted: May 11, 2010
First Posted: May 14, 2010
Results First Submitted: August 17, 2017
Results First Posted: September 15, 2017
Last Update Posted: September 15, 2017