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

• ClinicalTrials.gov Identifier: NCT00678886
• Recruitment Status: Completed
• First Posted: May 16, 2008
• Results First Posted: October 3, 2017
• Last Update Posted: October 3, 2017
• Sponsor: GlaxoSmithKline
• 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 infusion plus physician determined standard of care; Biological: placebo infusion plus physician determined standard of care
• Enrollment: 272

Participant Flow

Recruitment Details	This study was conducted at 85 centers in 9 countries namely Canada (4), Germany (3), Denmark (1), Spain (5), Finland (2), United Kingdom (4), Italy (8), Sweden (11) and United States of America (47) from 29 July 2008 to 31 January 2012. A total of 240 participants with new-onset Type 1 diabetes mellitus (NOT1DM) were planned to be enrolled.
Pre-assignment Details	Participants were screened for a period of 35 days and a total of 272 participants were randomized in the study.

Arm/Group Title	Adolescent (Placebo)	Adolescent (Otelixizumab)	Adult (Placebo)	Adult (Otelixizumab)
Arm/Group Description	Eligible adolescent participants received matching placebo to Otelixizumab administered as intravenous (IV) infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per Day over 8 consecutive days. Participants were followed-up for 24 months after the last dose.	Eligible adolescent participants received Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions as first dose (Day 1 of 0.1 milligram [mg], second dose (Day 2 of 0.2 mg), third dose (Day 3 of 0.3 mg), fourth, fifth, sixth, seventh and eight dose (on Days 4,5,6,7,8 of 0.5 mg per Day) 1 infusion per Day over 8 consecutive days . The total amount of Otelixizumab administered was 3.1 mg. Participants were followed-up for 24 months after the last dose.	Eligible adult participants received matching placebo to Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per day over 8 consecutive Days. Participants were followed-up for 24 months after the last dose.	Eligible adult participants received Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions as first dose (Day 1 of 0.1 mg), second dose (Day 2 of 0.2 mg), third dose (Day 3 of 0.3 mg), fourth, fifth, sixth, seventh and eight dose (on Days 4,5,6,7,8 of 0.5 mg per Day) 1 infusion per Day over 8 consecutive days . The total amount of Otelixizumab administered was 3.1 mg. Participants were followed-up for 24 months after the last dose.
Period Title: Overall Study
Started	10	19	81	162
Completed	10	19	72	153
Not Completed	0	0	9	9
Reason Not Completed
Withdrawal by Subject	0	0	4	6
Physician Decision	0	0	1	1
Lost to Follow-up	0	0	3	2
Other	0	0	1	0

Baseline Characteristics

Arm/Group Title		Placebo	Otelixizumab	Total
Arm/Group Description		Eligible participants received matching placebo to Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per Day over 8 consecutive days. Participants were followed-up for 24 months after the last dose.	Eligible participants received Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions as first dose (Day 1 of 0.1 mg, second dose (Day 2 of 0.2 mg), third dose (Day 3 of 0.3 mg), fourth, fifth, sixth, seventh and eight dose (on Days 4,5,6,7,8 of 0.5 mg per Day) 1 infusion per Day over 8 consecutive days . The total amount of Otelixizumab administered was 3.1 mg. Participants were followed-up for 24 months after the last dose.	Total of all reporting groups
Overall Number of Baseline Participants		91	181	272
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	91 participants	181 participants	272 participants
		25.2 (7.13)	24.7 (6.54)	24.9 (6.73)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	91 participants	181 participants	272 participants
	Female	31 34.1%	64 35.4%	95 34.9%
	Male	60 65.9%	117 64.6%	177 65.1%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	91 participants	181 participants	272 participants
	American Indian or Alaska Native	0 0.0%	1 0.6%	1 0.4%
	Asian	2 2.2%	1 0.6%	3 1.1%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	2 2.2%	6 3.3%	8 2.9%
	White	85 93.4%	169 93.4%	254 93.4%
	More than one race	2 2.2%	4 2.2%	6 2.2%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%

Outcome Measures

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
Description	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 reported AUC was normalized for time interval by dividing it by 120 minutes. This normalized AUC was calculated for each participant at Baseline, Week 12, and at Months 6, 12, 18, and 24. Data has been presented for meal stimulated C-peptide Area under assessment performed at Month 12. Baseline assessments were carried out on the morning of Day 1, before the start of the first infusion of study drug. Change from Baseline was calculated by subtracting the Baseline value from the post-randomization value at Month 12.
Time Frame	Baseline (0-120 minutes on Day 1) and Month 12 (0-120 minutes)

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population, comprised of all participants who were randomized and received any part of at least 1 infusion of study drug.

Arm/Group Title	Placebo	Otelixizumab
Arm/Group Description:	Eligible participants received matching placebo to Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per Day over 8 consecutive days. Participants were followed-up for 24 months after the last dose.	Eligible participants received Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions as first dose (Day 1 of 0.1 mg, second dose (Day 2 of 0.2 mg), third dose (Day 3 of 0.3 mg), fourth, fifth, sixth, seventh and eight dose (on Days 4,5,6,7,8 of 0.5 mg per Day) 1 infusion per Day over 8 consecutive days . The total amount of Otelixizumab administered was 3.1 mg. Participants were followed-up for 24 months after the last dose.
Overall Number of Participants Analyzed	91	181
Least Squares Mean (Standard Error); Unit of Measure: nanomoles per liter
	-0.21 (0.030)	-0.21 (0.021)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Otelixizumab
	Comments	Mixed meal-stimulated C-peptide AUC, Placebo Vs Otelixizumab at Month 12
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.813
	Comments	[Not Specified]
	Method	Mixed effects repeated measures model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.01
	Confidence Interval	(2-Sided) 95%; -0.06 to 0.08
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Number of Participants Who Were Responders for (Glycosylated Hemoglobin) HbA1c/Insulin Use Response at Week 12 and Months 6 and 12
Description	A participant was considered a responder if, at the given time point, the participant had HbA1c<= 6.5%, and mean daily insulin use over 7 consecutive days < 0.5 international units per kilogram per day (IU/kg/day) during the 2 weeks preceding the visit. Data has been presented from number of participants with their percentages who were responders at Week 12 and Months 6 and 12.
Time Frame	Week 12 and Months 6 and 12

Outcome Measure Data

Analysis Population Description

ITT population. Only those participants available at the specified time points were analyzed.

Arm/Group Title		Placebo	Otelixizumab
Arm/Group Description:		Eligible participants received matching placebo to Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per Day over 8 consecutive days. Participants were followed-up for 24 months after the last dose.	Eligible participants received Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions as first dose (Day 1 of 0.1 mg, second dose (Day 2 of 0.2 mg), third dose (Day 3 of 0.3 mg), fourth, fifth, sixth, seventh and eight dose (on Days 4,5,6,7,8 of 0.5 mg per Day) 1 infusion per Day over 8 consecutive days . The total amount of Otelixizumab administered was 3.1 mg. Participants were followed-up for 24 months after the last dose.
Overall Number of Participants Analyzed		91	181
Measure Type: Count of Participants; Unit of Measure: Participants
Responders at Week 12	Number Analyzed	78 participants	161 participants
		45 57.7%	85 52.8%
Responders at Month 6	Number Analyzed	76 participants	158 participants
		42 55.3%	74 46.8%
Responders at Month 12	Number Analyzed	80 participants	160 participants
		34 42.5%	56 35.0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Otelixizumab
	Comments	Percentage of responders, Placebo Vs Otelixizumab at Week 12
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.737
	Comments	[Not Specified]
	Method	Hochberg adjusted
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.90
	Confidence Interval	(2-Sided) 95%; 0.47 to 1.70
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Otelixizumab
	Comments	Percentage of responders, Placebo Vs Otelixizumab at Month 6
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.737
	Comments	[Not Specified]
	Method	Hochberg adjusted
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.77
	Confidence Interval	(2-Sided) 95%; 0.42 to 1.39
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Otelixizumab
	Comments	Percentage of responders, Placebo Vs Otelixizumab at Month 12
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.481
	Comments	[Not Specified]
	Method	Hochberg adjusted
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.81
	Confidence Interval	(2-Sided) 95%; 0.45 to 1.46
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	Mean Daily Insulin Use at Week 12 and Months 6 and 12.
Description	Participants recorded their daily insulin use in their electronic diaries. In particular, insulin was recorded thoroughly and accurately for at least 7 consecutive days during the 2 weeks before the visits at Baseline, Week 12, and Months 6 and 12. During each of these visits, the investigator/designee accessed the invivodata DiaryPRO web site to review insulin-use data for the previous 2-week period to ensure completeness. If errors/gaps were identified (e.g., if the participant did not take insulin and not entered 0 units), the investigator/designee recorded the missing data from participant recall using a data clarification form (DCF). Paper diary to collect insulin use, were reviewed for completeness. Any missing data that could be recalled by the participant was entered. If the participant did not record any insulin use during the 2-week period before the visit, the site obtained an insulin use history for the previous 7 days and calculated the average daily insulin dose.
Time Frame	Week 12 and Months 6 and 12.

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Placebo	Otelixizumab
Arm/Group Description:	Eligible participants received matching placebo to Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per Day over 8 consecutive days. Participants were followed-up for 24 months after the last dose.	Eligible participants received Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions as first dose (Day 1 of 0.1 mg, second dose (Day 2 of 0.2 mg), third dose (Day 3 of 0.3 mg), fourth, fifth, sixth, seventh and eight dose (on Days 4,5,6,7,8 of 0.5 mg per Day) 1 infusion per Day over 8 consecutive days . The total amount of Otelixizumab administered was 3.1 mg. Participants were followed-up for 24 months after the last dose.
Overall Number of Participants Analyzed	91	181
Least Squares Mean (Standard Error); Unit of Measure: IU/kg
Mean daily insulin use at Week 12	0.34 (0.017)	0.31 (0.013)
Mean daily insulin use at Month 6	0.36 (0.022)	0.36 (0.016)
Mean daily insulin use at Month 12	0.42 (0.023)	0.39 (0.017)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Otelixizumab
	Comments	Mean insulin use, Placebo Vs Otelixizumab at Week 12
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.281
	Comments	[Not Specified]
	Method	Mixed effects repeated measures model
	Comments	Mixed effects repeated measures models was adjusted for age, continent, and baseline parameter value.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.03
	Confidence Interval	(2-Sided) 95%; -0.07 to 0.01
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Otelixizumab
	Comments	Mean insulin use, Placebo Vs Otelixizumab at Month 6
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.969
	Comments	[Not Specified]
	Method	Mixed effects repeated measures model
	Comments	Mixed effects repeated measures models was adjusted for age, continent, and baseline parameter value.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.00
	Confidence Interval	(2-Sided) 95%; -0.05 to 0.05
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Otelixizumab
	Comments	Mean insulin use, Placebo Vs Otelixizumab at Month 12
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.272
	Comments	[Not Specified]
	Method	Mixed effects repeated measures model
	Comments	Mixed effects repeated measures models was adjusted for age, continent, and baseline parameter value.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.03
	Confidence Interval	(2-Sided) 95%; -0.08 to 0.02
	Estimation Comments	[Not Specified]

4. Secondary Outcome

Title	HbA1c Level at Week 12 and Months 6 and 12
Description	HbA1c levels were recorded at Screening, Baseline (Day 1), Day 28, Week 8, Week 12, Months 4 to 12 and Month 24. Data has been presented for HbA1c levels at Week 12 and Months 6 and 12.
Time Frame	Week 12 and Months 6 and 12

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Placebo	Otelixizumab
Arm/Group Description:	Eligible participants received matching placebo to Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per Day over 8 consecutive days. Participants were followed-up for 24 months after the last dose.	Eligible participants received Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions as first dose (Day 1 of 0.1 mg, second dose (Day 2 of 0.2 mg), third dose (Day 3 of 0.3 mg), fourth, fifth, sixth, seventh and eight dose (on Days 4,5,6,7,8 of 0.5 mg per Day) 1 infusion per Day over 8 consecutive days . The total amount of Otelixizumab administered was 3.1 mg. Participants were followed-up for 24 months after the last dose.
Overall Number of Participants Analyzed	91	181
Least Squares Mean (Standard Error); Unit of Measure: Percentage
HbA1c levels at Month 12	6.83 (0.146)	7.02 (0.108)
HbA1c levels at Month 6	6.60 (0.138)	6.77 (0.100)
HbA1c levels at Week 12	6.45 (0.124)	6.54 (0.094)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Otelixizumab
	Comments	HbA1c levels, Placebo Vs Otelixizumab at Month 12
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.289
	Comments	[Not Specified]
	Method	Mixed effects repeated measures model
	Comments	Mixed effects repeated measures models was adjusted for age, continent, and baseline parameter value.
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	0.18
	Confidence Interval	(2-Sided) 95%; -0.16 to 0.52
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Otelixizumab
	Comments	HbA1c levels, Placebo Vs Otelixizumab at Month 6
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.538
	Comments	[Not Specified]
	Method	Mixed effects repeated measures model
	Comments	Mixed effects repeated measures models was adjusted for age, continent, and baseline parameter value.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.17
	Confidence Interval	(2-Sided) 95%; -0.15 to 0.49
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Otelixizumab
	Comments	HbA1c levels, Placebo Vs Otelixizumab at Week 12
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.538
	Comments	[Not Specified]
	Method	Mixed effects repeated measures model
	Comments	Mixed effects repeated measures models was adjusted for age, continent, and baseline parameter value.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.09
	Confidence Interval	(2-Sided) 95%; -0.19 to 0.36
	Estimation Comments	[Not Specified]

5. Secondary Outcome

Title	Number of Hypoglycemic Events Defined by Hypoglycemic Event Categories From Baseline Upto Month 12
Description	Hypoglycemic events reported by participants were classified as defined by the American Diabetes Association (ADA) Workgroup on Hypoglycemia as follows: Severe hypoglycemia: an event requiring assistance of another person to actively administer carbohydrate, glucagon/other resuscitative actions, documented symptomatic hypoglycemia: an event during which typical symptoms of hypoglycemia are accompanied by a measured plasma glucose concentration(PGC)<=70 mg/dL, asymptomatic hypoglycemia: an event not accompanied by typical symptoms of hypoglycemia but with a measured PGC<=70 mg/dL,probable symptomatic hypoglycemia: an event during which symptoms of hypoglycemia are not accompanied by a plasma glucose determination, but were presumably caused by a PGC<=70 mg/dL and relative hypoglycemia: an event during which the person with diabetes reports any of the typical symptoms of hypoglycemia, and interprets the symptoms as indicative of hypoglycemia, but with a measured PGC>70 mg/dL.
Time Frame	Upto Month 12

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Placebo	Otelixizumab
Arm/Group Description:	Eligible participants received matching placebo to Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per Day over 8 consecutive days. Participants were followed-up for 24 months after the last dose.	Eligible participants received Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions as first dose (Day 1 of 0.1 mg, second dose (Day 2 of 0.2 mg), third dose (Day 3 of 0.3 mg), fourth, fifth, sixth, seventh and eight dose (on Days 4,5,6,7,8 of 0.5 mg per Day) 1 infusion per Day over 8 consecutive days . The total amount of Otelixizumab administered was 3.1 mg. Participants were followed-up for 24 months after the last dose.
Overall Number of Participants Analyzed	91	181
Measure Type: Number; Unit of Measure: Hypoglycemic events
Severe hypoglycemia upto Month 12	2	5
Documented symptomatic hypoglycemia upto Month 12	3092	6322
Asymptomatic hypoglycemia upto Month 12	4718	9962
Probable symptomatic hypoglycemia upto Month 12	84	93
Relative hypoglycemia upto Month 12	85	211

6. Secondary Outcome

Title	Number of Participants With Hypoglycemic Events Defined by Hypoglycemic Event Categories From Baseline Upto Month 12
Description	Hypoglycemic events reported by participants were classified as defined by the ADA Workgroup on Hypoglycemia as Severe hypoglycemia: an event requiring assistance of another person to actively administer carbohydrate, glucagon/other resuscitative actions, documented symptomatic hypoglycemia: an event during which typical symptoms of hypoglycemia are accompanied by a measured plasma glucose concentration (PGC)<=70 mg/dL, asymptomatic hypoglycemia: an event not accompanied by typical symptoms of hypoglycemia but with a measured PGC<=70 mg/dL,probable symptomatic hypoglycemia: an event during which symptoms of hypoglycemia are not accompanied by a plasma glucose determination, but were presumably caused by a PGC<=70 mg/dL and relative hypoglycemia: an event during which the person with diabetes reports any of the typical symptoms of hypoglycemia, and interprets the symptoms as indicative of hypoglycemia, but with a measured PGC>70 mg/dL. Only categories with values are presented.
Time Frame	Upto Month 12

Outcome Measure Data

Analysis Population Description

ITT population. Data has been presented for number of participants with their percentages with hypoglycemic events defined by hypoglycemic event categories from Baseline upto month 12.

Arm/Group Title	Placebo	Otelixizumab
Arm/Group Description:	Eligible participants received matching placebo to Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per Day over 8 consecutive days. Participants were followed-up for 24 months after the last dose.	Eligible participants received Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions as first dose (Day 1 of 0.1 mg, second dose (Day 2 of 0.2 mg), third dose (Day 3 of 0.3 mg), fourth, fifth, sixth, seventh and eight dose (on Days 4,5,6,7,8 of 0.5 mg per Day) 1 infusion per Day over 8 consecutive days . The total amount of Otelixizumab administered was 3.1 mg. Participants were followed-up for 24 months after the last dose.
Overall Number of Participants Analyzed	91	181
Measure Type: Count of Participants; Unit of Measure: Participants
Severe hypoglycemia upto Month 12	2 2.2%	4 2.2%
Documented symptomatic hypoglycemia upto Month 12	78 85.7%	163 90.1%
Asymptomatic hypoglycemia upto Month 12	10 11.0%	13 7.2%

7. Secondary Outcome

Title	Number of Hypoglycemic Excursions (<=70 mg/dL) With Most Complete Glucose at Week 12 and Months 6 and 12.
Description	The event frequency of glucose measurements that were hypoglycemic excursions were calculated per participant basis, using the number of occurrences where blood glucose was less than or equal to 70 mg/dL. Most complete glucose interval was the 7 day period with the maximum number of days with at least 4 recordings per day. If these results were in more than one 7 day period, then the 7 day period with the largest average number of daily recordings (out of those with the maximum number of days with at least 4 recordings per day) was selected. If there were 2 or more 7 day periods that have the same number of days with at least 4 recordings and the same maximum average number of glucose recordings, the period that ended closest to the day of the study was selected.
Time Frame	Week 12 and Months 6 and 12.

Outcome Measure Data

Analysis Population Description

ITT population. Only those participants available at the specified time points were analyzed.

Arm/Group Title		Placebo	Otelixizumab
Arm/Group Description:		Eligible participants received matching placebo to Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per Day over 8 consecutive days. Participants were followed-up for 24 months after the last dose.	Eligible participants received Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions as first dose (Day 1 of 0.1 mg, second dose (Day 2 of 0.2 mg), third dose (Day 3 of 0.3 mg), fourth, fifth, sixth, seventh and eight dose (on Days 4,5,6,7,8 of 0.5 mg per Day) 1 infusion per Day over 8 consecutive days . The total amount of Otelixizumab administered was 3.1 mg. Participants were followed-up for 24 months after the last dose.
Overall Number of Participants Analyzed		91	181
Mean (Standard Error); Unit of Measure: Hypoglycemic excursions
Number of hypoglycemic excursions at Week 12	Number Analyzed	90 participants	177 participants
		2.3 (0.28)	2.8 (0.27)
Number of hypoglycemic excursions at Month 6	Number Analyzed	80 participants	166 participants
		3.0 (0.36)	2.9 (0.27)
Number of hypoglycemic excursions at Month 12	Number Analyzed	78 participants	161 participants
		2.9 (0.41)	3.2 (0.32)

8. Secondary Outcome

Title	Magnitude of Greatest Hypoglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12.
Description	The greatest hypoglycemic excursions during an interval was calculated as 70 mg/dL minus the lowest recorded glucose level in the interval. If a participant had data recorded during the interval but did not have a value below 70 mg/dL, the participants greatest hypoglycemic excursion for that interval was 0 mg/dL. Most complete glucose interval was the 7 day period with the maximum number of days with at least 4 recordings per day. If these results were in more than one 7 day period, then the 7 day period with the largest average number of daily recordings (out of those with the maximum number of days with at least 4 recordings per day) was selected. If there were 2 or more 7 day periods that have the same number of days with at least 4 recordings and the same maximum average number of glucose recordings, the period that ended closest to the day of the study was selected.
Time Frame	Week 12 and Months 6 and 12.

Outcome Measure Data

Analysis Population Description

ITT population. Only those participants available at the specified time points were analyzed.

Arm/Group Title		Placebo	Otelixizumab
Arm/Group Description:		Eligible participants received matching placebo to Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per Day over 8 consecutive days. Participants were followed-up for 24 months after the last dose.	Eligible participants received Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions as first dose (Day 1 of 0.1 mg, second dose (Day 2 of 0.2 mg), third dose (Day 3 of 0.3 mg), fourth, fifth, sixth, seventh and eight dose (on Days 4,5,6,7,8 of 0.5 mg per Day) 1 infusion per Day over 8 consecutive days . The total amount of Otelixizumab administered was 3.1 mg. Participants were followed-up for 24 months after the last dose.
Overall Number of Participants Analyzed		91	181
Mean (Standard Error); Unit of Measure: milligrams per deciliter
Magnitude of excursion, Week 12	Number Analyzed	90 participants	177 participants
		9.4 (0.92)	10.8 (0.90)
Magnitude of excursion, Month 6	Number Analyzed	80 participants	166 participants
		11.9 (1.24)	10.6 (0.77)
Magnitude of excursion, Month 12	Number Analyzed	78 participants	161 participants
		11.2 (1.20)	11.0 (0.92)

9. Secondary Outcome

Title	Number of Participants With Hypoglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12
Description	Percentage of hypoglycemic excursions was calculated as the total number of observations that exceed the hypoglycemic excursion boundary (i.e.<= 70 mg/dL) divided by the total number of glucose measurements recorded in a time interval for the intervals: Baseline to Week 12, post-Week 12 to Month 6, post-Month 6 to Month 12. Most complete glucose interval was the 7 day period with the maximum number of days with at least 4 recordings per day. If these results were in more than one 7 day period, then the 7 day period with the largest average number of daily recordings (out of those with the maximum number of days with at least 4 recordings per day) was selected. If there were 2 or more 7 day periods that have the same number of days with at least 4 recordings and the same maximum average number of glucose recordings, the period that ended closest to the day of the study was selected. Data has been presented for number of participants with their percentages having hypoglycemic excursion.
Time Frame	Week 12 and Months 6 and 12

Outcome Measure Data

Analysis Population Description

ITT population. Only those participants available at the specified time points were analyzed.

Arm/Group Title		Placebo	Otelixizumab
Arm/Group Description:		Eligible participants received matching placebo to Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per Day over 8 consecutive days. Participants were followed-up for 24 months after the last dose.	Eligible participants received Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions as first dose (Day 1 of 0.1 mg, second dose (Day 2 of 0.2 mg), third dose (Day 3 of 0.3 mg), fourth, fifth, sixth, seventh and eight dose (on Days 4,5,6,7,8 of 0.5 mg per Day) 1 infusion per Day over 8 consecutive days . The total amount of Otelixizumab administered was 3.1 mg. Participants were followed-up for 24 months after the last dose.
Overall Number of Participants Analyzed		91	181
Measure Type: Count of Participants; Unit of Measure: Participants
Percentage of participants with excursion,Week 12	Number Analyzed	90 participants	177 participants
		72 80.0%	127 71.8%
Percentage of participants with excursion,Month 6	Number Analyzed	80 participants	166 participants
		57 71.3%	121 72.9%
Percentage of participants with excursion,Month 12	Number Analyzed	78 participants	161 participants
		56 71.8%	111 68.9%

10. Secondary Outcome

Title	Number of Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12.
Description	The event frequency of glucose measurements that were hyperglycemic excursions were calculated on a per participant basis using the number of occurrences where blood glucose was greater than the hyperglycemic tolerance limit. There were 3 hyperglycemic tolerance limits considered: 200 mg/dL, 130 mg/dL and 100 mg/dL. Most complete glucose interval was the 7 day period with the maximum number of days with at least 4 recordings per day. If these results were in more than one 7 day period, then the 7 day period with the largest average number of daily recordings (out of those with the maximum number of days with at least 4 recordings per day) was selected. If there were 2 or more 7 day periods that have the same number of days with at least 4 recordings and the same maximum average number of glucose recordings, the period that ended closest to the day of the study was selected.
Time Frame	Week 12 and Months 6 and 12

Outcome Measure Data

Analysis Population Description

ITT population. Only those participants available at the specified time points were analyzed.

Arm/Group Title		Placebo	Otelixizumab
Arm/Group Description:		Eligible participants received matching placebo to Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per Day over 8 consecutive days. Participants were followed-up for 24 months after the last dose	Eligible participants received Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions as first dose (Day 1 of 0.1 mg, second dose (Day 2 of 0.2 mg), third dose (Day 3 of 0.3 mg), fourth, fifth, sixth, seventh and eight dose (on Days 4,5,6,7,8 of 0.5 mg per Day) 1 infusion per Day over 8 consecutive days . The total amount of Otelixizumab administered was 3.1 mg. Participants were followed-up for 24 months after the last dose.
Overall Number of Participants Analyzed		91	181
Mean (Standard Error); Unit of Measure: Hyperglycemic excursions
Threshold > 100 mg/dL at Week 12	Number Analyzed	90 participants	177 participants
		34.0 (1.78)	32.9 (1.15)
Threshold > 130 mg/dL at Week 12	Number Analyzed	90 participants	177 participants
		20.5 (1.72)	19.9 (1.01)
Threshold > 200 mg/dL at Week 12	Number Analyzed	90 participants	177 participants
		5.7 (0.85)	5.6 (0.59)
Threshold > 100 mg/dL at Month 6	Number Analyzed	80 participants	166 participants
		33.5 (1.77)	35.1 (1.41)
Threshold > 130 mg/dL at Month 6	Number Analyzed	80 participants	166 participants
		20.8 (1.68)	22.7 (1.25)
Threshold > 200 mg/dL at Month 6	Number Analyzed	80 participants	166 participants
		6.5 (1.07)	7.9 (0.85)
Threshold > 100 mg/dL at Month 12	Number Analyzed	78 participants	161 participants
		35.6 (1.97)	33.4 (1.27)
Threshold > 130 mg/dL at Month 12	Number Analyzed	78 participants	161 participants
		24.0 (1.92)	22.2 (1.05)
Threshold > 200 mg/dL at Month 12	Number Analyzed	78 participants	161 participants
		8.6 (1.42)	6.9 (0.59)

11. Secondary Outcome

Title	Magnitude of Greatest Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12.
Description	The greatest hyperglycemic excursions during an interval was calculated as the largest recorded glucose level in the interval minus the hyperglycemic tolerance limit value (HGTLV). If a participant had data recorded during the interval but did not have a value above the HGTLV, the participants greatest hyperglycemic excursion for that interval was 0 mg/dL. Most complete glucose interval was the 7 day period with the maximum number of days with at least 4 recordings per day. If these results were in more than one 7 day period, then the 7 day period with the largest average number of daily recordings (out of those with the maximum number of days with at least 4 recordings per day) was selected. If there were 2 or more 7 day periods that have the same number of days with at least 4 recordings and the same maximum average number of glucose recordings, the period that ended closest to the day of the study was selected.
Time Frame	Week 12 and Months 6 and 12.

Outcome Measure Data

Analysis Population Description

ITT population. Only those participants available at the specified time points were analyzed.

Arm/Group Title		Placebo	Otelixizumab
Arm/Group Description:		Eligible participants received matching placebo to Otelixizumab administered as IV infusions, 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 administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions (as first dose-day 1 of 0.1 mg, second dose-day 2 of 0.2 mg, third dose-day 3 of 0.3 mg, fourth, fifth, sixth, seventh and eight dose on days 4,5,6,7,8 of 0.5 mg per day) 1 infusion per day over 8 consecutive days . The total amount of Otelixizumab administered was 3.1 mg.
Overall Number of Participants Analyzed		91	181
Mean (Standard Error); Unit of Measure: milligrams per deciliter
Threshold> 100 mg/dL at Week 12	Number Analyzed	90 participants	177 participants
		158.3 (9.26)	158.4 (6.65)
Threshold> 130 mg/dL at Week 12	Number Analyzed	90 participants	177 participants
		128.3 (9.26)	128.4 (6.65)
Threshold> 200 mg/dL at Week 12	Number Analyzed	90 participants	177 participants
		65.7 (8.51)	65.7 (6.12)
Threshold> 100 mg/dL at Month 6	Number Analyzed	80 participants	166 participants
		154.6 (9.34)	175.7 (8.09)
Threshold> 130 mg/dL at Month 6	Number Analyzed	80 participants	166 participants
		124.8 (9.31)	145.7 (8.09)
Threshold> 200 mg/dL at Month 6	Number Analyzed	80 participants	166 participants
		63.3 (8.32)	80.1 (7.75)
Threshold> 100 mg/dL at Month 12	Number Analyzed	78 participants	161 participants
		176.7 (10.02)	177.5 (7.08)
Threshold> 130 mg/dL at Month 12	Number Analyzed	78 participants	161 participants
		146.8 (10.00)	147.5 (7.07)
Threshold> 200 mg/dL at Month 12	Number Analyzed	78 participants	161 participants
		81.8 (9.33)	82.6 (6.61)

12. Secondary Outcome

Title	Number of Participants With Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12
Description	Percentage of hyperglycemic excursions was calculated as the total number of observations that exceed the hyperglycemic excursion boundary (i.e. > HGTLV) divided by the total number of glucose measurements recorded in a time interval for the intervals: Baseline to Week 12, post-Week 12 to Month 6, post-Month 6 to Month 12. Most complete glucose interval was the 7 day period with the maximum number of days with at least 4 recordings per day. If these results were in more than one 7 day period, then the 7 day period with the largest average number of daily recordings (out of those with the maximum number of days with at least 4 recordings per day) was selected. If there were 2 or more 7 day periods that have the same number of days with at least 4 recordings and the same maximum average number of glucose recordings, the period that ended closest to the day of the study was selected. Data for number of participants with their percentages are presented.
Time Frame	Week 12 and Months 6 and 12

Outcome Measure Data

Analysis Population Description

ITT population. Only those participants available at the specified time points were analyzed.

Arm/Group Title		Placebo	Otelixizumab
Arm/Group Description:		Eligible participants received matching placebo to Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per Day over 8 consecutive days. Participants were followed-up for 24 months after the last dose.	Eligible participants received Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions as first dose (Day 1 of 0.1 mg, second dose (Day 2 of 0.2 mg), third dose (Day 3 of 0.3 mg), fourth, fifth, sixth, seventh and eight dose (on Days 4,5,6,7,8 of 0.5 mg per Day) 1 infusion per Day over 8 consecutive days . The total amount of Otelixizumab administered was 3.1 mg. Participants were followed-up for 24 months after the last dose.
Overall Number of Participants Analyzed		91	181
Measure Type: Count of Participants; Unit of Measure: Participants
Threshold> 100 mg/dL at Week 12	Number Analyzed	90 participants	177 participants
		90 100.0%	177 100.0%
Threshold> 130 mg/dL at Week 12	Number Analyzed	90 participants	177 participants
		90 100.0%	177 100.0%
Threshold> 200 mg/dL at Week 12	Number Analyzed	90 participants	177 participants
		65 72.2%	130 73.4%
Threshold> 100 mg/dL at Month 6	Number Analyzed	80 participants	166 participants
		80 100.0%	166 100.0%
Threshold> 130 mg/dL at Month 6	Number Analyzed	80 participants	166 participants
		79 98.8%	166 100.0%
Threshold> 200 mg/dL at Month 6	Number Analyzed	80 participants	166 participants
		57 71.3%	139 83.7%
Threshold> 100 mg/dL at Month 12	Number Analyzed	78 participants	161 participants
		78 100.0%	161 100.0%
Threshold> 130 mg/dL at Month 12	Number Analyzed	78 participants	161 participants
		77 98.7%	160 99.4%
Threshold> 200 mg/dL at Month 12	Number Analyzed	78 participants	161 participants
		60 76.9%	131 81.4%

13. Secondary Outcome

Title	Change From Baseline in Average Daily Risk Range (ADRR) at Week 12 and Months 6 and 12.
Description	Average daily risk range is a measure for evaluation of blood glucose variability that was designed to be equally sensitive to hypoglycemia and hyperglycemia. The ADRR was assessed over 30-day periods prior to Baseline and at key visits Week 12 and Months 6 and 12. Baseline assessments were carried out on the morning of Day 1, before the start of the first infusion of study drug. Change from Baseline was calculated by subtracting the Baseline value from the post-randomization value at Week 12 and Months 6 and 12.
Time Frame	Baseline (Day 1) and Week 12, Months 6 and 12.

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	Placebo	Otelixizumab
Arm/Group Description:	Eligible participants received matching placebo to Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per Day over 8 consecutive days. Participants were followed-up for 24 months after the last dose.	Eligible participants received Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions as first dose (Day 1 of 0.1 mg, second dose (Day 2 of 0.2 mg), third dose (Day 3 of 0.3 mg), fourth, fifth, sixth, seventh and eight dose (on Days 4,5,6,7,8 of 0.5 mg per Day) 1 infusion per Day over 8 consecutive days . The total amount of Otelixizumab administered was 3.1 mg. Participants were followed-up for 24 months after the last dose.
Overall Number of Participants Analyzed	91	181
Least Squares Mean (Standard Error); Unit of Measure: Ratio
ADRR at Week 12	-0.41 (0.826)	0.71 (0.599)
ADRR at Month 6	2.03 (1.133)	2.86 (0.801)
ADRR at Month 12	3.29 (1.038)	4.22 (0.732)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Otelixizumab
	Comments	ADRR, Placebo Vs Otelixizumab at Week 12
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.540
	Comments	[Not Specified]
	Method	Mixed effects repeated measures model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Median Difference (Net)
	Estimated Value	1.12
	Confidence Interval	(2-Sided) 95%; -0.88 to 3.11
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Otelixizumab
	Comments	ADRR, Placebo Vs Otelixizumab at Month 6
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.546
	Comments	[Not Specified]
	Method	Mixed effects repeated measures model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.83
	Confidence Interval	(2-Sided) 95%; -1.89 to 3.56
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Otelixizumab
	Comments	ADRR, Placebo Vs Otelixizumab at Month 12
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.462
	Comments	[Not Specified]
	Method	Mixed effects repeated measures model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.93
	Confidence Interval	(2-Sided) 95%; -1.56 to 3.42
	Estimation Comments	[Not Specified]

14. Secondary Outcome

Title	Composite Rank Summary for HbA1c and Exogenous Insulin Use at Month 6 and Month 12
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, 12. For the O'Brien mean rank analysis at a particular time point, adjusted HbA1c values (for both treatment groups together) was ranked from smallest to largest, and adjusted mean daily insulin use values were 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.
Time Frame	Month 6 and 12

Outcome Measure Data

Analysis Population Description

ITT population. Only those participants available at the specified time points were analyzed.

Arm/Group Title		Placebo	Otelixizumab
Arm/Group Description:		Eligible participants received matching placebo to Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per Day over 8 consecutive days. Participants were followed-up for 24 months after the last dose.	Eligible participants received Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions as first dose (Day 1 of 0.1 mg, second dose (Day 2 of 0.2 mg), third dose (Day 3 of 0.3 mg), fourth, fifth, sixth, seventh and eight dose (on Days 4,5,6,7,8 of 0.5 mg per Day) 1 infusion per Day over 8 consecutive days . The total amount of Otelixizumab administered was 3.1 mg. Participants were followed-up for 24 months after the last dose.
Overall Number of Participants Analyzed		91	181
Mean (Standard Deviation); Unit of Measure: Composite rank score
Composite rank summary, Month 6	Number Analyzed	73 participants	156 participants
		238 (123.3)	247 (113.7)
Composite rank summary, Month 12	Number Analyzed	76 participants	158 participants
		245 (120.0)	244 (115.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Otelixizumab
	Comments	Composite Rank Summary for HbA1c and Exogenous Insulin Use, Placebo Vs Otelixizumab at Month 6
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.957
	Comments	[Not Specified]
	Method	Hochberg-adjusted
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Otelixizumab
	Comments	Composite Rank Summary for HbA1c and Exogenous Insulin Use, Placebo Vs Otelixizumab at Month 12
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.957
	Comments	[Not Specified]
	Method	Hochberg-adjusted
	Comments	[Not Specified]

15. Secondary Outcome

Title	Composite Rank Summary for C-Peptide AUC, HbA1c and Exogenous Insulin Use at Month 6 and Month 12
Description	O'Brien analyses will be 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 and12. For the O'Brien mean rank analysis at a particular time point, HbA1c and insulin use will be ranked from smallest to largest, and C-peptide AUC will be ranked from largest to smallest. For each participant, the C-Peptide AUC, ranks for HbA1c and insulin use were added together, producing a composite rank. A treatment comparison test was then performed on the composite ranks.
Time Frame	Month 6 and 12

Outcome Measure Data

Analysis Population Description

ITT population. Only those participants available at the specified time points were analyzed.

Arm/Group Title		Placebo	Otelixizumab
Arm/Group Description:		Eligible participants received matching placebo to Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per Day over 8 consecutive days. Participants were followed-up for 24 months after the last dose.	Eligible participants received Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions as first dose (Day 1 of 0.1 mg, second dose (Day 2 of 0.2 mg), third dose (Day 3 of 0.3 mg), fourth, fifth, sixth, seventh and eight dose (on Days 4,5,6,7,8 of 0.5 mg per Day) 1 infusion per Day over 8 consecutive days . The total amount of Otelixizumab administered was 3.1 mg. Participants were followed-up for 24 months after the last dose.
Overall Number of Participants Analyzed		91	181
Mean (Standard Deviation); Unit of Measure: Composite rank score
Month 6	Number Analyzed	72 participants	151 participants
		365 (83.8)	373 (105.6)
Month 12	Number Analyzed	74 participants	151 participants
		360 (85.1)	366 (95.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Otelixizumab
	Comments	Composite Rank Summary for C-Peptide AUC, HbA1c and Exogenous Insulin Use, Placebo Vs Otelixizumab at Month 6
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.653
	Comments	[Not Specified]
	Method	Hochberg-adjusted
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Otelixizumab
	Comments	Composite Rank Summary for C-Peptide AUC, HbA1c and Exogenous Insulin Use, Placebo Vs Otelixizumab at Month 12
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.653
	Comments	[Not Specified]
	Method	Hochberg-adjusted
	Comments	[Not Specified]

16. Secondary Outcome

Title	Change From Baseline in Level of Cytokines Interleukin (IL-6), IL-10 and Tumor Necrosis Factor-alpha (TNF-a) at Day 1, Day 4, Day 8
Description	Levels of cytokine (TNFα, IL-6, IL-10) were measured at Baseline and at 2 hours after end of infusion (EOI) on Day 1, Day 4, Day 8 . Baseline assessments were carried out on the morning of Day 1, before the start of the first infusion of study drug. Change from Baseline was calculated by subtracting the Baseline value from the post-randomization value at Day 1, Day 4 and Day 8.
Time Frame	Day 1, Day 4, Day 8

Outcome Measure Data

Analysis Population Description

ITT population. Only those participants available at the specified time points were analyzed.

Arm/Group Title		Placebo	Otelixizumab
Arm/Group Description:		Eligible participants received matching placebo to Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per Day over 8 consecutive days. Participants were followed-up for 24 months after the last dose.	Eligible participants received Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions as first dose (Day 1 of 0.1 mg, second dose (Day 2 of 0.2 mg), third dose (Day 3 of 0.3 mg), fourth, fifth, sixth, seventh and eight dose (on Days 4,5,6,7,8 of 0.5 mg per Day) 1 infusion per Day over 8 consecutive days . The total amount of Otelixizumab administered was 3.1 mg. Participants were followed-up for 24 months after the last dose.
Overall Number of Participants Analyzed		91	181
Mean (Standard Error); Unit of Measure: picograms per milliliter
IL-6 levels, Day 1, 2 hours after EOI	Number Analyzed	24 participants	50 participants
		0.76 (0.680)	2.78 (0.544)
IL-6 levels, Day 4, 2 hours after EOI	Number Analyzed	24 participants	44 participants
		-0.13 (0.251)	3.01 (1.107)
IL-6 levels, Day 8, 2 hours after EOI	Number Analyzed	23 participants	50 participants
		0.45 (0.448)	14.59 (5.266)
IL-10 levels, Day 1, 2 hours after EOI	Number Analyzed	23 participants	50 participants
		0.15 (0.342)	4.61 (1.770)
IL-10 levels, Day 4, 2 hours after EOI	Number Analyzed	23 participants	44 participants
		0.55 (0.629)	1.35 (0.575)
IL-10 levels, Day 8, 2 hours after EOI	Number Analyzed	22 participants	49 participants
		1.84 (1.019)	25.57 (7.196)
TNF-a levels, Day 1, 2 hours after EOI	Number Analyzed	24 participants	50 participants
		-0.126 (0.0719)	2.320 (0.3996)
TNF-a levels, Day 4, 2 hours after EOI	Number Analyzed	24 participants	44 participants
		0.111 (0.2381)	1.509 (0.5740)
TNF-a levels, Day 8, 2 hours after EOI	Number Analyzed	23 participants	50 participants
		0.135 (0.2649)	3.614 (0.8920)

17. Secondary Outcome

Title	Percent Change From Baseline in Circulating Peripheral Lymphocytes CD4+CD25+FoxP3+ T Cells and CD4+CD25hiFoxP3+ T Cells in Type 1 Diabetes Mellitus (TIDM) up to Month 12
Description	Blood samples were drawn for lymphocyte subset evaluations at Baseline and at 2hours after EOI on Day 4, pre-dose and after E0I on Day 8, Day 14, Day 21, Day 28, Week 6, Week 8, Week 10, Week 12, Month 6 and Month 12. Percentages of relevant lymphocyte subsets were determined by flow cytometry. The lymphocyte subsets assessed included CD8+CD25+ T lymphocytes, as well as the subsets of lymphocytes of these type that were positive for FoxP3, a protein that was expressed at high levels in the cytoplasm of regulatory T cells. CD4+CD25hiFoxP3+ T lymphocytes, a cell type was of interest because it played a regulatory role in T1DM. Baseline assessments were carried out on the morning of Day 1, before the start of the first infusion of study drug. Change from Baseline was calculated by subtracting the Baseline value from the post-randomization value at the time of assessment.
Time Frame	Baseline (pre-dose on Day 1) and up to 12 Months

Outcome Measure Data

Analysis Population Description

ITT population. Only those participants available at the specified time points were analyzed.

Arm/Group Title		Placebo	Otelixizumab
Arm/Group Description:		Eligible participants received matching placebo to Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per Day over 8 consecutive days. Participants were followed-up for 24 months after the last dose.	Eligible participants received Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions as first dose (Day 1 of 0.1 mg, second dose (Day 2 of 0.2 mg), third dose (Day 3 of 0.3 mg), fourth, fifth, sixth, seventh and eight dose (on Days 4,5,6,7,8 of 0.5 mg per Day) 1 infusion per Day over 8 consecutive days . The total amount of Otelixizumab administered was 3.1 mg. Participants were followed-up for 24 months after the last dose.
Overall Number of Participants Analyzed		91	181
Median (Full Range); Unit of Measure: Percent change
CD4+CD25+FoxP3+ T, Day 4, 2 hours after EOI	Number Analyzed	28 participants	56 participants
		118.8; (32.1 to 366.9)	53.4; (3.4 to 235.9)
CD4+CD25+FoxP3+ T, Day 8 pre-dose	Number Analyzed	27 participants	57 participants
		94.4; (25.9 to 199.9)	49.7; (9.4 to 148.5)
CD4+CD25+FoxP3+ T, Day 8, 2 hours after EOI	Number Analyzed	70 participants	146 participants
		113.2; (28.8 to 2127.6)	40.1; (2.1 to 3737.0)
CD4+CD25+FoxP3+ T, Day 14	Number Analyzed	72 participants	153 participants
		114.5; (26.5 to 2384.4)	101.3; (15.5 to 10906.4)
CD4+CD25+FoxP3+ T, Day 21	Number Analyzed	74 participants	147 participants
		114.6; (34.8 to 489.8)	101.9; (0.0 to 44228.1)
CD4+CD25+FoxP3+ T, Day 28	Number Analyzed	75 participants	151 participants
		95.1; (7.0 to 1612.7)	101.7; (2.1 to 6363.7)
CD4+CD25+FoxP3+ T, Week 6	Number Analyzed	72 participants	148 participants
		104.1; (0.0 to 514.2)	106.6; (0.0 to 7010.9)
CD4+CD25+FoxP3+ T, Week 8	Number Analyzed	75 participants	156 participants
		110.1; (29.1 to 1602.3)	107.1; (4.7 to 15806.4)
CD4+CD25+FoxP3+ T, Week 10	Number Analyzed	75 participants	145 participants
		109.9; (8.6 to 1820.9)	102.7; (7.4 to 9943.6)
CD4+CD25+FoxP3+ T, Week 12	Number Analyzed	75 participants	150 participants
		102.5; (9.8 to 1018.7)	85.5; (2.9 to 9911.7)
CD4+CD25+FoxP3+ T, Month 6	Number Analyzed	72 participants	146 participants
		137.9; (19.5 to 1409.6)	133.3; (19.8 to 10357.4)
CD4+CD25+FoxP3+ T, Month 12	Number Analyzed	70 participants	149 participants
		122.0; (9.5 to 628.7)	106.9; (0.4 to 31690.3)
CD4+CD25hiFoxP3+ T Cells, Day 4, 2 hours after EOI	Number Analyzed	28 participants	56 participants
		151.9; (12.6 to 400.8)	60.8; (1.5 to 364.5)
CD4+CD25hiFoxP3+ T Cells, Day 8 pre-dose	Number Analyzed	27 participants	57 participants
		93.8; (13.6 to 521.7)	43.5; (3.6 to 675.0)
CD4+CD25hiFoxP3+ T Cells, Day 8, 2 hours after EOI	Number Analyzed	69 participants	146 participants
		110.7; (18.6 to 3577.8)	35.9; (0.0 to 321279)
CD4+CD25hiFoxP3+ T Cells, Day 14	Number Analyzed	71 participants	153 participants
		118.4; (8.8 to 1502.5)	109.7; (5.8 to 1364664)
CD4+CD25hiFoxP3+ T Cells, Day 21	Number Analyzed	74 participants	147 participants
		110.0; (9.7 to 1720.2)	98.8; (0.0 to 1479653)
CD4+CD25hiFoxP3+ T Cells, Day 28	Number Analyzed	74 participants	151 participants
		101.1; (2.1 to 949.9)	108.7; (0.0 to 62190.9)
CD4+CD25hiFoxP3+ T Cells, Week 6	Number Analyzed	72 participants	148 participants
		106.9; (0.0 to 2508.7)	110.7; (0.0 to 9573.5)
CD4+CD25hiFoxP3+ T Cells, Week 8	Number Analyzed	74 participants	156 participants
		131.7; (14.1 to 843.2)	120.3; (0.5 to 175040)
CD4+CD25hiFoxP3+ T Cells, Week 10	Number Analyzed	74 participants	145 participants
		97.7; (1.5 to 2356.8)	107.0; (0.0 to 128591)
CD4+CD25hiFoxP3+ T Cells, Week 12	Number Analyzed	74 participants	150 participants
		113.6; (1.9 to 1310.2)	90.9; (0.1 to 1045228)
CD4+CD25hiFoxP3+ T Cells, Month 6	Number Analyzed	71 participants	146 participants
		150.9; (6.1 to 25639.5)	153.2; (5.5 to 1544544)
CD4+CD25hiFoxP3+ T Cells, Month 12	Number Analyzed	69 participants	149 participants
		166.4; (5.1 to 1748.9)	160.6; (0.0 to 78843.4)

18. Secondary Outcome

Title	Percent Change From Baseline in Cell-bound Otelixizumab on CD4+ T Cells at Day 1, Day 4, Day 8
Description	The amount of cell-bound otelixizumab was determined by flow cytometry. The extent of T cell receptor alpha beta (TCRαβ) expression was determined using an antibody that bound to TCRαβ but did not compete with otelixizumab for binding sites at the expected range of concentrations. The MESF of the anti-TCRαβ antibody was used to quantify the number of CD3/TCR complexes present on T cells. Free otelixizumab binding sites (sites not occupied by otelixizumab) were detected by staining with biotinylated otelixizumab. The MESF of bound biotinylated otelixizumab was directly proportional to the availability of free otelixizumab binding sites. MESF of bound antibody on CD4+ T cells was a direct measurement of cell-bound otelixizumab on CD4+ T cells. Baseline assessments were carried out on the morning of Day 1, before the start of the first infusion of study drug. Change from Baseline was calculated by subtracting the Baseline value from the post-randomization value at Day 1, Day 4 and Day 8.
Time Frame	Baseline (pre-dose on Day 1), Day 4 and Day 8

Outcome Measure Data

Analysis Population Description

ITT population. Only those participants available at the specified time points were analyzed.

Arm/Group Title		Placebo	Otelixizumab
Arm/Group Description:		Eligible participants received matching placebo to Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per Day over 8 consecutive days. Participants were followed-up for 24 months after the last dose.	Eligible participants received Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions as first dose (Day 1 of 0.1 mg, second dose (Day 2 of 0.2 mg), third dose (Day 3 of 0.3 mg), fourth, fifth, sixth, seventh and eight dose (on Days 4,5,6,7,8 of 0.5 mg per Day) 1 infusion per Day over 8 consecutive days . The total amount of Otelixizumab administered was 3.1 mg. Participants were followed-up for 24 months after the last dose.
Overall Number of Participants Analyzed		91	181
Mean (Standard Error); Unit of Measure: Percent change
CD4+ T cells, Day 1, 2 hours after EOI	Number Analyzed	20 participants	57 participants
		125.1 (18.00)	914.8 (269.18)
CD4+ T cells, Day 4, 2 hours after EOI	Number Analyzed	23 participants	54 participants
		174.3 (41.95)	2719.8 (369.41)
CD4+ T cells, Day 8, pre-dose	Number Analyzed	26 participants	54 participants
		151.5 (39.49)	471.5 (98.53)
CD4+ T cells, Day 8, 2 hours after EOI	Number Analyzed	26 participants	57 participants
		167.9 (47.67)	1387.5 (274.21)

19. Secondary Outcome

Title	Percent Change From Baseline in CD3/TCR Saturation on CD4+ T Cells and CD8+ T Cells at Day 1, Day 4, Day 8
Description	The extent of saturation of CD3/TCR receptors on CD4+ and CD8+ lymphocytes was determined by flow cytometry. The extent of TCRαβ expression was determined using an antibody that bound to TCRαβ but did not compete with otelixizumab for binding sites at the expected range of concentrations. The MESF of the anti-TCRαβ antibody was used to quantify the number of CD3/TCR complexes present on T cells. The MESF of bound biotinylated otelixizumab was directly proportional to the availability of free otelixizumab binding sites. MESF of free CD3 sites on CD4+ T cells and CD8+ T cells was direct measurement of saturation of the CD3/TCR complex on CD4+ T cells and CD8+ T cells. Baseline assessments were carried out on the morning of Day 1, before the start of the first infusion of study drug. Change from Baseline was calculated by subtracting the Baseline value from the post-randomization value at Day 1, Day 4 and Day 8.
Time Frame	Baseline (Pre-dose Day 1), Day 4, Day 8

Outcome Measure Data

Analysis Population Description

ITT population. Only those participants available at the specified time points were analyzed.

Arm/Group Title		Placebo	Otelixizumab
Arm/Group Description:		Eligible participants received matching placebo to Otelixizumab administered as IV infusions, 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 administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions (as first dose-day 1 of 0.1 mg, second dose-day 2 of 0.2 mg, third dose-day 3 of 0.3 mg, fourth, fifth, sixth, seventh and eight dose on days 4,5,6,7,8 of 0.5 mg per day) 1 infusion per day over 8 consecutive days . The total amount of Otelixizumab administered was 3.1 mg.
Overall Number of Participants Analyzed		91	181
Mean (Standard Error); Unit of Measure: Percent change
CD4+ T cells, Day 1, 2 hours after EOI	Number Analyzed	20 participants	57 participants
		93.4 (2.40)	90.9 (3.82)
CD4+ T cells, Day 4, 2 hours after EOI	Number Analyzed	23 participants	54 participants
		109.7 (11.91)	50.2 (4.90)
CD4+ T cells, Day 8, pre-dose	Number Analyzed	26 participants	54 participants
		97.7 (10.66)	59.0 (5.31)
CD4+ T cells, Day 8, 2 hours after EOI	Number Analyzed	26 participants	56 participants
		98.0 (13.03)	21.7 (3.33)
CD8+ T cells, Day 1, 2 hours after EOI	Number Analyzed	20 participants	57 participants
		92.4 (2.38)	91.4 (3.82)
CD8+ T cells, Day 4, 2 hours after EOI	Number Analyzed	23 participants	54 participants
		116.7 (14.53)	51.6 (5.23)
CD8+ T cells, Day 8, pre-dose	Number Analyzed	26 participants	54 participants
		97.4 (11.84)	60.8 (6.11)
CD8+ T cells, Day 8, 2 hours after EOI	Number Analyzed	26 participants	56 participants
		98.2 (14.63)	23.0 (3.72)

20. Secondary Outcome

Title	Percent Change From Baseline in CD3/TCR Modulation on CD4+ T Cells and CD8+ T Cells at Day 1, Day 4, Day 8
Description	The extent of modulation of CD3/TCR receptors on CD4+ and CD8+ lymphocytes was determined by flow cytometry. The extent of TCRαβ expression was determined using an antibody that bound to TCRαβ but did not compete with otelixizumab for binding sites at the expected range of concentrations. The MESF of the anti-TCRαβ antibody was used to quantify the number of CD3/TCR complexes present on T cells. The MESF of bound biotinylated otelixizumab was directly proportional to the availability of free otelixizumab binding sites.CD3/TCR complexes on CD4+ and CD8+ T cells were detected with a non-competing antibody. Changes in the MESF of TCR expression was a direct measurement of TCR modulation. Baseline assessments were carried out on the morning of Day 1, before the start of the first infusion of study drug. Change from Baseline was calculated by subtracting the Baseline value from the post-randomization value at Day 1, Day 4 and Day 8.
Time Frame	Baseline (Pre-dose Day 1), Day 4, Day 8

Outcome Measure Data

Analysis Population Description

ITT population. Only those participants available at the specified time points were analyzed.

Arm/Group Title		Placebo	Otelixizumab
Arm/Group Description:		Eligible participants received matching placebo to Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per Day over 8 consecutive days. Participants were followed-up for 24 months after the last dose.	Eligible participants received Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions as first dose (Day 1 of 0.1 mg, second dose (Day 2 of 0.2 mg), third dose (Day 3 of 0.3 mg), fourth, fifth, sixth, seventh and eight dose (on Days 4,5,6,7,8 of 0.5 mg per Day) 1 infusion per Day over 8 consecutive days . The total amount of Otelixizumab administered was 3.1 mg. Participants were followed-up for 24 months after the last dose.
Overall Number of Participants Analyzed		91	181
Mean (Standard Error); Unit of Measure: Percent change
CD4+ T cells, Day 1, 2 hours after EOI	Number Analyzed	20 participants	57 participants
		94.2 (2.95)	91.1 (2.90)
CD4+ T cells, Day 4, 2 hours after EOI	Number Analyzed	23 participants	54 participants
		103.8 (8.93)	70.8 (3.89)
CD4+ T cells, Day 8, pre-dose	Number Analyzed	26 participants	54 participants
		101.4 (6.09)	61.0 (2.65)
CD4+ T cells, Day 8, 2 hours after EOI	Number Analyzed	26 participants	57 participants
		103.4 (5.87)	32.2 (2.52)
CD8+ T cells, Day 1, 2 hours after EOI	Number Analyzed	20 participants	57 participants
		95.2 (2.72)	93.7 (3.06)
CD8+ T cells, Day 4, 2 hours after EOI	Number Analyzed	23 participants	54 participants
		111.1 (10.56)	77.1 (4.33)
CD8+ T cells, Day 8, pre-dose	Number Analyzed	26 participants	54 participants
		101.8 (6.19)	62.3 (2.68)
CD8+ T cells, Day 8, 2 hours after EOI	Number Analyzed	26 participants	57 participants
		103.0 (6.05)	36.2 (2.52)

Adverse Events

Time Frame	Upto Month 24
Adverse Event Reporting Description	Safety was used for analysis which comprised of all participants who received any part of at least 1 infusion of study drug.
Arm/Group Title	Placebo		Otelixizumab
Arm/Group Description	Eligible participants received matching placebo to Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per Day over 8 consecutive days. Participants were followed-up for 24 months after the last dose.		Eligible participants received Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions as first dose (Day 1 of 0.1 mg, second dose (Day 2 of 0.2 mg), third dose (Day 3 of 0.3 mg), fourth, fifth, sixth, seventh and eight dose (on Days 4,5,6,7,8 of 0.5 mg per Day) 1 infusion per Day over 8 consecutive days . The total amount of Otelixizumab administered was 3.1 mg. Participants were followed-up for 24 months after the last dose.
All-Cause Mortality
	Placebo		Otelixizumab
	Affected / at Risk (%)		Affected / at Risk (%)
Total	0/91 (0.00%)		0/181 (0.00%)
Serious Adverse Events
	Placebo		Otelixizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/91 (6.59%)		15/181 (8.29%)
Gastrointestinal disorders
Anal fistula † 1	0/91 (0.00%)		1/181 (0.55%)
Gastritis erosive † 1	0/91 (0.00%)		1/181 (0.55%)
Hepatobiliary disorders
Cholelithiasis † 1	1/91 (1.10%)		0/181 (0.00%)
Immune system disorders
Cytokine release syndrome † 1	0/91 (0.00%)		3/181 (1.66%)
Infections and infestations
Anal abscess † 1	0/91 (0.00%)		1/181 (0.55%)
Appendicitis † 1	1/91 (1.10%)		0/181 (0.00%)
Gastroenteritis viral † 1	1/91 (1.10%)		0/181 (0.00%)
Septic embolus † 1	0/91 (0.00%)		1/181 (0.55%)
Tonsillitis † 1	1/91 (1.10%)		0/181 (0.00%)
Viral upper respiratory tract infection † 1	1/91 (1.10%)		0/181 (0.00%)
Injury, poisoning and procedural complications
Alcohol poisoning † 1	0/91 (0.00%)		1/181 (0.55%)
Ligament rupture † 1	0/91 (0.00%)		1/181 (0.55%)
Road traffic accident † 1	0/91 (0.00%)		1/181 (0.55%)
Metabolism and nutrition disorders
Hypoglycaemia † 1	0/91 (0.00%)		1/181 (0.55%)
Hypoglycaemic seizure † 1	0/91 (0.00%)		1/181 (0.55%)
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion † 1	0/91 (0.00%)		1/181 (0.55%)
Nervous system disorders
Neurological symptom † 1	1/91 (1.10%)		0/181 (0.00%)
Paraesthesia † 1	0/91 (0.00%)		1/181 (0.55%)
Pregnancy, puerperium and perinatal conditions
Abortion missed † 1	0/91 (0.00%)		1/181 (0.55%)
Psychiatric disorders
Alcohol abuse † 1	0/91 (0.00%)		1/181 (0.55%)
Major depression † 1	1/91 (1.10%)		0/181 (0.00%)
1 Term from vocabulary, MedDRA; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Placebo		Otelixizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	81/91 (89.01%)		173/181 (95.58%)
Blood and lymphatic system disorders
Lymphadenopathy † 1	13/91 (14.29%)	20	18/181 (9.94%)	37
Gastrointestinal disorders
Nausea † 1	20/91 (21.98%)	32	60/181 (33.15%)	91
Vomiting † 1	13/91 (14.29%)	15	35/181 (19.34%)	40
Diarrhoea † 1	8/91 (8.79%)	9	13/181 (7.18%)	19
General disorders
Fatigue † 1	20/91 (21.98%)	32	42/181 (23.20%)	58
Pyrexia † 1	10/91 (10.99%)	10	34/181 (18.78%)	45
Chills † 1	6/91 (6.59%)	9	24/181 (13.26%)	32
Malaise † 1	2/91 (2.20%)	2	10/181 (5.52%)	13
Infections and infestations
Nasopharyngitis † 1	29/91 (31.87%)	42	48/181 (26.52%)	83
Upper respiratory tract infection † 1	10/91 (10.99%)	15	22/181 (12.15%)	29
Sinusitis † 1	4/91 (4.40%)	4	12/181 (6.63%)	17
Pharyngitis † 1	9/91 (9.89%)	13	4/181 (2.21%)	4
Viral infection † 1	6/91 (6.59%)	9	3/181 (1.66%)	4
Investigations
Blood creatine phosphokinase increased † 1	6/91 (6.59%)	6	8/181 (4.42%)	8
Metabolism and nutrition disorders
Hypoglycaemia † 1	8/91 (8.79%)	16	22/181 (12.15%)	83
Musculoskeletal and connective tissue disorders
Myalgia † 1	14/91 (15.38%)	27	21/181 (11.60%)	32
Arthralgia † 1	2/91 (2.20%)	4	20/181 (11.05%)	23
Back pain † 1	5/91 (5.49%)	5	13/181 (7.18%)	16
Pain in extremity † 1	5/91 (5.49%)	5	9/181 (4.97%)	11
Nervous system disorders
Headache † 1	45/91 (49.45%)	117	155/181 (85.64%)	441
Dizziness † 1	12/91 (13.19%)	20	18/181 (9.94%)	23
Psychiatric disorders
Insomnia † 1	5/91 (5.49%)	5	5/181 (2.76%)	6
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain † 1	24/91 (26.37%)	35	25/181 (13.81%)	35
Cough † 1	10/91 (10.99%)	11	19/181 (10.50%)	24
Nasal congestion † 1	7/91 (7.69%)	9	8/181 (4.42%)	13
Rhinorrhoea † 1	2/91 (2.20%)	2	10/181 (5.52%)	11
Sinus congestion † 1	5/91 (5.49%)	5	5/181 (2.76%)	7
Skin and subcutaneous tissue disorders
Rash macular † 1	3/91 (3.30%)	3	10/181 (5.52%)	17
Rash papular † 1	0/91 (0.00%)	0	12/181 (6.63%)	15
1 Term from vocabulary, MedDRA; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

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

Publications:

Keymeulen B, Vandemeulebroucke E, Ziegler AG, Mathieu C, Kaufman L, Hale G, Gorus F, Goldman M, Walter M, Candon S, Schandene L, Crenier L, De Block C, Seigneurin JM, De Pauw P, Pierard D, Weets I, Rebello P, Bird P, Berrie E, Frewin M, Waldmann H, Bach JF, Pipeleers D, Chatenoud L. Insulin needs after CD3-antibody therapy in new-onset type 1 diabetes. N Engl J Med. 2005 Jun 23;352(25):2598-608.

You S, Candon S, Kuhn C, Bach JF, Chatenoud L. CD3 antibodies as unique tools to restore self-tolerance in established autoimmunity their mode of action and clinical application in type 1 diabetes. Adv Immunol. 2008;100:13-37. doi: 10.1016/S0065-2776(08)00802-X. Review.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00678886
• Obsolete Identifiers: NCT00893022
• Other Study ID Numbers: 115495; TRX4006 ( Other Identifier: Tolerx )
• First Submitted: May 13, 2008
• First Posted: May 16, 2008
• Results First Submitted: July 19, 2017
• Results First Posted: October 3, 2017
• Last Update Posted: October 3, 2017