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

Durable-Response Therapy Evaluation For Early or New-Onset Type 1 Diabetes - DEFEND

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00678886

Acronym

DEFEND-1

Enrollment

272

Registered

2008-05-16

Start date

2008-07-29

Completion date

2012-01-31

Last updated

2017-10-03

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Diabetes Mellitus, Type 1

Keywords

Type 1 diabetes, new onset type 1 diabetes, T1DM, Type l diabetes, juvenile diabetes

Brief summary

The purpose of this study is to find out if an 8-day series of otelixizumab infusions leads to greater improvement in insulin secretion as compared with placebo infusion. Insulin secretion will be assessed using mixed meal-stimulated C-peptide. Subjects will be assigned to receive either otelixizumab or placebo at a ratio of 2:1 (2/3 otelixizumab, 1/3 placebo). These study agents will be administered as an addition to insulin, diet, and other physician determined standard of care treatments. DEFEND-1 is now closed to enrollment. DEFEND-2 will begin early in 2010. It is very similar to DEFEND-1 and will again require subjects with new onset type 1 diabetes. Please check back here for more details. In the meantime, established and new onset type 1 diabetes patients in North America are welcome to consider the TTEDD study: http://www.clinicaltrials.gov/ct2/show/NCT00451321?term=TTEDD&rank=1

Detailed description

The following visits are required: * Screening Visits: 2 to 3 appointments will be conducted to determine eligibility. At 2 of these visits participants will drink a liquid meal and have blood tests done over the post-meal period. * Dosing Visits: 8 outpatient visits on consecutive days, each lasting about 4-6 hours. * Follow-up Visits: weekly for the first month, then every 2 weeks for 3 months, followed by monthly visits through 1 year. There will be 3 visits in the second year. * The total duration of the study is 2 years. * Glucose test strips, glucose monitors and PDAs to record insulin will be provided to all study subjects for the duration fo the study. Frequent glycemic monitoring will occur through lab testing and blood glucose self-monitoring to help facilitate tight glycemic control in all subjects.

Interventions

BIOLOGICALotelixizumab infusion plus physician determined standard of care

infusion

BIOLOGICALplacebo infusion plus physician determined standard of care

infusion

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

12 Years to 45 Years

Healthy volunteers

Inclusion criteria

* Ages 12-45 * Diagnosis of diabetes mellitus, consistent with ADA criteria * No more than 90 days between diagnosis and administration of study compounds * Requires insulin for type 1 diabetes mellitus, or has required insulin at some time between diagnosis and administration of study compounds. * Stimulated C-peptide level greater than 0.20 nmol/L and less than or equal to 3.50 nmol/L * Positive for one or more of the autoantibodies typically associated with T1DM: antibody to glutamic acid decarboxylase (anti-GAD); antibody to protein tyrosine phosphatase-like protein (anti-IA-2); zinc transporter autoantibodies (ZNT8); insulin autoantibodies (IAA). A subject who is positive for insulin autoantibodies (IAA) and negative for the other autoantibodies will only be eligible if the subject has used insulin for less than 7 days total.

Exclusion criteria

* Other, significant medical conditions based on the study doctor's evaluation

Design outcomes

Primary

Measure	Time frame	Description
Change From Baseline in 2-hour Mixed Meal Stimulated C-peptide Area Under Curve [AUC] (Normalized for 120-minute Time Interval) at Month 12	Baseline (0-120 minutes on Day 1) and Month 12 (0-120 minutes)	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.

Secondary

Measure	Time frame	Description
Mean Daily Insulin Use at Week 12 and Months 6 and 12.	Week 12 and Months 6 and 12.	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.
HbA1c Level at Week 12 and Months 6 and 12	Week 12 and Months 6 and 12	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.
Number of Hypoglycemic Events Defined by Hypoglycemic Event Categories From Baseline Upto Month 12	Upto Month 12	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.
Number of Participants With Hypoglycemic Events Defined by Hypoglycemic Event Categories From Baseline Upto Month 12	Upto Month 12	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.
Number of Hypoglycemic Excursions (<=70 mg/dL) With Most Complete Glucose at Week 12 and Months 6 and 12.	Week 12 and Months 6 and 12.	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.
Magnitude of Greatest Hypoglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12.	Week 12 and Months 6 and 12.	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.
Number of Participants With Hypoglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12	Week 12 and Months 6 and 12	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.
Number of Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12.	Week 12 and Months 6 and 12	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.
Magnitude of Greatest Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12.	Week 12 and Months 6 and 12.	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.
Number of Participants Who Were Responders for (Glycosylated Hemoglobin) HbA1c/Insulin Use Response at Week 12 and Months 6 and 12	Week 12 and Months 6 and 12	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.
Change From Baseline in Average Daily Risk Range (ADRR) at Week 12 and Months 6 and 12.	Baseline (Day 1) and Week 12, Months 6 and 12.	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.
Composite Rank Summary for HbA1c and Exogenous Insulin Use at Month 6 and Month 12	Month 6 and 12	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.
Composite Rank Summary for C-Peptide AUC, HbA1c and Exogenous Insulin Use at Month 6 and Month 12	Month 6 and 12	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.
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	Day 1, Day 4, Day 8	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.
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	Baseline (pre-dose on Day 1) and up to 12 Months	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.
Percent Change From Baseline in Cell-bound Otelixizumab on CD4+ T Cells at Day 1, Day 4, Day 8	Baseline (pre-dose on Day 1), Day 4 and Day 8	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.
Percent Change From Baseline in CD3/TCR Saturation on CD4+ T Cells and CD8+ T Cells at Day 1, Day 4, Day 8	Baseline (Pre-dose Day 1), Day 4, Day 8	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.
Percent Change From Baseline in CD3/TCR Modulation on CD4+ T Cells and CD8+ T Cells at Day 1, Day 4, Day 8	Baseline (Pre-dose Day 1), Day 4, Day 8	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.
Number of Participants With Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12	Week 12 and Months 6 and 12	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.

Countries

Canada, Denmark, Finland, Germany, Italy, Spain, Sweden, United Kingdom, United States

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.

Participants by arm

Arm	Count
Placebo 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.	91
Otelixizumab 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.	181
Total	272

Withdrawals & dropouts

Period	Reason	FG002	FG003
Overall Study	Lost to Follow-up	3	2
Overall Study	Other	1	0
Overall Study	Physician Decision	1	1
Overall Study	Withdrawal by Subject	4	6

Baseline characteristics

Characteristic	Otelixizumab	Total	Placebo
Age, Continuous	24.7 Years STANDARD_DEVIATION 6.54	24.9 Years STANDARD_DEVIATION 6.73	25.2 Years STANDARD_DEVIATION 7.13
Race (NIH/OMB) American Indian or Alaska Native	1 Participants	1 Participants	0 Participants
Race (NIH/OMB) Asian	1 Participants	3 Participants	2 Participants
Race (NIH/OMB) Black or African American	6 Participants	8 Participants	2 Participants
Race (NIH/OMB) More than one race	4 Participants	6 Participants	2 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	169 Participants	254 Participants	85 Participants
Sex: Female, Male Female	64 Participants	95 Participants	31 Participants
Sex: Female, Male Male	117 Participants	177 Participants	60 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 91	0 / 181
other Total, other adverse events	81 / 91	173 / 181
serious Total, serious adverse events	6 / 91	15 / 181

Outcome results

Primary

Change From Baseline in 2-hour Mixed Meal Stimulated C-peptide Area Under Curve [AUC] (Normalized for 120-minute Time Interval) at Month 12

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)

Population: 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	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Placebo	Change From Baseline in 2-hour Mixed Meal Stimulated C-peptide Area Under Curve [AUC] (Normalized for 120-minute Time Interval) at Month 12	-0.21 nanomoles per liter	Standard Error 0.03
Otelixizumab	Change From Baseline in 2-hour Mixed Meal Stimulated C-peptide Area Under Curve [AUC] (Normalized for 120-minute Time Interval) at Month 12	-0.21 nanomoles per liter	Standard Error 0.021

Comparison: Mixed meal-stimulated C-peptide AUC, Placebo Vs Otelixizumab at Month 12p-value: 0.81395% CI: [-0.06, 0.08]Mixed effects repeated measures model

Secondary

Change From Baseline in Average Daily Risk Range (ADRR) at Week 12 and Months 6 and 12.

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.

Population: ITT population.

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Placebo	Change From Baseline in Average Daily Risk Range (ADRR) at Week 12 and Months 6 and 12.	ADRR at Week 12	-0.41 Ratio	Standard Error 0.826
Placebo	Change From Baseline in Average Daily Risk Range (ADRR) at Week 12 and Months 6 and 12.	ADRR at Month 6	2.03 Ratio	Standard Error 1.133
Placebo	Change From Baseline in Average Daily Risk Range (ADRR) at Week 12 and Months 6 and 12.	ADRR at Month 12	3.29 Ratio	Standard Error 1.038
Otelixizumab	Change From Baseline in Average Daily Risk Range (ADRR) at Week 12 and Months 6 and 12.	ADRR at Month 6	2.86 Ratio	Standard Error 0.801
Otelixizumab	Change From Baseline in Average Daily Risk Range (ADRR) at Week 12 and Months 6 and 12.	ADRR at Week 12	0.71 Ratio	Standard Error 0.599
Otelixizumab	Change From Baseline in Average Daily Risk Range (ADRR) at Week 12 and Months 6 and 12.	ADRR at Month 12	4.22 Ratio	Standard Error 0.732

Comparison: ADRR, Placebo Vs Otelixizumab at Week 12p-value: 0.5495% CI: [-0.88, 3.11]Mixed effects repeated measures model

Comparison: ADRR, Placebo Vs Otelixizumab at Month 6p-value: 0.54695% CI: [-1.89, 3.56]Mixed effects repeated measures model

Comparison: ADRR, Placebo Vs Otelixizumab at Month 12p-value: 0.46295% CI: [-1.56, 3.42]Mixed effects repeated measures model

Secondary

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

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

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

Arm	Measure	Group	Value (MEAN)	Dispersion
Placebo	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	IL-10 levels, Day 4, 2 hours after EOI	0.55 picograms per milliliter	Standard Error 0.629
Placebo	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	IL-6 levels, Day 4, 2 hours after EOI	-0.13 picograms per milliliter	Standard Error 0.251
Placebo	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	IL-10 levels, Day 8, 2 hours after EOI	1.84 picograms per milliliter	Standard Error 1.019
Placebo	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	TNF-a levels, Day 8, 2 hours after EOI	0.135 picograms per milliliter	Standard Error 0.2649
Placebo	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	TNF-a levels, Day 1, 2 hours after EOI	-0.126 picograms per milliliter	Standard Error 0.0719
Placebo	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	IL-6 levels, Day 8, 2 hours after EOI	0.45 picograms per milliliter	Standard Error 0.448
Placebo	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	TNF-a levels, Day 4, 2 hours after EOI	0.111 picograms per milliliter	Standard Error 0.2381
Placebo	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	IL-6 levels, Day 1, 2 hours after EOI	0.76 picograms per milliliter	Standard Error 0.68
Placebo	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	IL-10 levels, Day 1, 2 hours after EOI	0.15 picograms per milliliter	Standard Error 0.342
Otelixizumab	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	TNF-a levels, Day 8, 2 hours after EOI	3.614 picograms per milliliter	Standard Error 0.892
Otelixizumab	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	IL-10 levels, Day 1, 2 hours after EOI	4.61 picograms per milliliter	Standard Error 1.77
Otelixizumab	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	IL-6 levels, Day 4, 2 hours after EOI	3.01 picograms per milliliter	Standard Error 1.107
Otelixizumab	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	IL-6 levels, Day 8, 2 hours after EOI	14.59 picograms per milliliter	Standard Error 5.266
Otelixizumab	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	IL-10 levels, Day 4, 2 hours after EOI	1.35 picograms per milliliter	Standard Error 0.575
Otelixizumab	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	IL-10 levels, Day 8, 2 hours after EOI	25.57 picograms per milliliter	Standard Error 7.196
Otelixizumab	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	TNF-a levels, Day 1, 2 hours after EOI	2.320 picograms per milliliter	Standard Error 0.3996
Otelixizumab	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	TNF-a levels, Day 4, 2 hours after EOI	1.509 picograms per milliliter	Standard Error 0.574
Otelixizumab	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	IL-6 levels, Day 1, 2 hours after EOI	2.78 picograms per milliliter	Standard Error 0.544

Secondary

Composite Rank Summary for C-Peptide AUC, HbA1c and Exogenous Insulin Use at Month 6 and Month 12

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

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

Arm	Measure	Group	Value (MEAN)	Dispersion
Placebo	Composite Rank Summary for C-Peptide AUC, HbA1c and Exogenous Insulin Use at Month 6 and Month 12	Month 6	365 Composite rank score	Standard Deviation 83.8
Placebo	Composite Rank Summary for C-Peptide AUC, HbA1c and Exogenous Insulin Use at Month 6 and Month 12	Month 12	360 Composite rank score	Standard Deviation 85.1
Otelixizumab	Composite Rank Summary for C-Peptide AUC, HbA1c and Exogenous Insulin Use at Month 6 and Month 12	Month 6	373 Composite rank score	Standard Deviation 105.6
Otelixizumab	Composite Rank Summary for C-Peptide AUC, HbA1c and Exogenous Insulin Use at Month 6 and Month 12	Month 12	366 Composite rank score	Standard Deviation 95.4

Comparison: Composite Rank Summary for C-Peptide AUC, HbA1c and Exogenous Insulin Use, Placebo Vs Otelixizumab at Month 6p-value: 0.653Hochberg-adjusted

Comparison: Composite Rank Summary for C-Peptide AUC, HbA1c and Exogenous Insulin Use, Placebo Vs Otelixizumab at Month 12p-value: 0.653Hochberg-adjusted

Secondary

Composite Rank Summary for HbA1c and Exogenous Insulin Use at Month 6 and Month 12

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

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

Arm	Measure	Group	Value (MEAN)	Dispersion
Placebo	Composite Rank Summary for HbA1c and Exogenous Insulin Use at Month 6 and Month 12	Composite rank summary, Month 6	238 Composite rank score	Standard Deviation 123.3
Placebo	Composite Rank Summary for HbA1c and Exogenous Insulin Use at Month 6 and Month 12	Composite rank summary, Month 12	245 Composite rank score	Standard Deviation 120
Otelixizumab	Composite Rank Summary for HbA1c and Exogenous Insulin Use at Month 6 and Month 12	Composite rank summary, Month 6	247 Composite rank score	Standard Deviation 113.7
Otelixizumab	Composite Rank Summary for HbA1c and Exogenous Insulin Use at Month 6 and Month 12	Composite rank summary, Month 12	244 Composite rank score	Standard Deviation 115.2

Comparison: Composite Rank Summary for HbA1c and Exogenous Insulin Use, Placebo Vs Otelixizumab at Month 6p-value: 0.957Hochberg-adjusted

Comparison: Composite Rank Summary for HbA1c and Exogenous Insulin Use, Placebo Vs Otelixizumab at Month 12p-value: 0.957Hochberg-adjusted

Secondary

HbA1c Level at Week 12 and Months 6 and 12

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

Population: ITT population.

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Placebo	HbA1c Level at Week 12 and Months 6 and 12	HbA1c levels at Month 12	6.83 Percentage	Standard Error 0.146
Placebo	HbA1c Level at Week 12 and Months 6 and 12	HbA1c levels at Month 6	6.60 Percentage	Standard Error 0.138
Placebo	HbA1c Level at Week 12 and Months 6 and 12	HbA1c levels at Week 12	6.45 Percentage	Standard Error 0.124
Otelixizumab	HbA1c Level at Week 12 and Months 6 and 12	HbA1c levels at Month 12	7.02 Percentage	Standard Error 0.108
Otelixizumab	HbA1c Level at Week 12 and Months 6 and 12	HbA1c levels at Month 6	6.77 Percentage	Standard Error 0.1
Otelixizumab	HbA1c Level at Week 12 and Months 6 and 12	HbA1c levels at Week 12	6.54 Percentage	Standard Error 0.094

Comparison: HbA1c levels, Placebo Vs Otelixizumab at Month 12p-value: 0.28995% CI: [-0.16, 0.52]Mixed effects repeated measures model

Comparison: HbA1c levels, Placebo Vs Otelixizumab at Month 6p-value: 0.53895% CI: [-0.15, 0.49]Mixed effects repeated measures model

Comparison: HbA1c levels, Placebo Vs Otelixizumab at Week 12p-value: 0.53895% CI: [-0.19, 0.36]Mixed effects repeated measures model

Secondary

Magnitude of Greatest Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12.

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.

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

Arm	Measure	Group	Value (MEAN)	Dispersion
Placebo	Magnitude of Greatest Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12.	Threshold> 200 mg/dL at Week 12	65.7 milligrams per deciliter	Standard Error 8.51
Placebo	Magnitude of Greatest Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12.	Threshold> 130 mg/dL at Month 6	124.8 milligrams per deciliter	Standard Error 9.31
Placebo	Magnitude of Greatest Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12.	Threshold> 200 mg/dL at Month 6	63.3 milligrams per deciliter	Standard Error 8.32
Placebo	Magnitude of Greatest Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12.	Threshold> 130 mg/dL at Week 12	128.3 milligrams per deciliter	Standard Error 9.26
Placebo	Magnitude of Greatest Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12.	Threshold> 100 mg/dL at Month 12	176.7 milligrams per deciliter	Standard Error 10.02
Placebo	Magnitude of Greatest Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12.	Threshold> 100 mg/dL at Month 6	154.6 milligrams per deciliter	Standard Error 9.34
Placebo	Magnitude of Greatest Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12.	Threshold> 130 mg/dL at Month 12	146.8 milligrams per deciliter	Standard Error 10
Placebo	Magnitude of Greatest Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12.	Threshold> 200 mg/dL at Month 12	81.8 milligrams per deciliter	Standard Error 9.33
Placebo	Magnitude of Greatest Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12.	Threshold> 100 mg/dL at Week 12	158.3 milligrams per deciliter	Standard Error 9.26
Otelixizumab	Magnitude of Greatest Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12.	Threshold> 200 mg/dL at Month 12	82.6 milligrams per deciliter	Standard Error 6.61
Otelixizumab	Magnitude of Greatest Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12.	Threshold> 130 mg/dL at Month 6	145.7 milligrams per deciliter	Standard Error 8.09
Otelixizumab	Magnitude of Greatest Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12.	Threshold> 130 mg/dL at Month 12	147.5 milligrams per deciliter	Standard Error 7.07
Otelixizumab	Magnitude of Greatest Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12.	Threshold> 100 mg/dL at Week 12	158.4 milligrams per deciliter	Standard Error 6.65
Otelixizumab	Magnitude of Greatest Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12.	Threshold> 130 mg/dL at Week 12	128.4 milligrams per deciliter	Standard Error 6.65
Otelixizumab	Magnitude of Greatest Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12.	Threshold> 200 mg/dL at Week 12	65.7 milligrams per deciliter	Standard Error 6.12
Otelixizumab	Magnitude of Greatest Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12.	Threshold> 100 mg/dL at Month 6	175.7 milligrams per deciliter	Standard Error 8.09
Otelixizumab	Magnitude of Greatest Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12.	Threshold> 200 mg/dL at Month 6	80.1 milligrams per deciliter	Standard Error 7.75
Otelixizumab	Magnitude of Greatest Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12.	Threshold> 100 mg/dL at Month 12	177.5 milligrams per deciliter	Standard Error 7.08

Secondary

Magnitude of Greatest Hypoglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12.

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.

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

Arm	Measure	Group	Value (MEAN)	Dispersion
Placebo	Magnitude of Greatest Hypoglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12.	Magnitude of excursion, Week 12	9.4 milligrams per deciliter	Standard Error 0.92
Placebo	Magnitude of Greatest Hypoglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12.	Magnitude of excursion, Month 6	11.9 milligrams per deciliter	Standard Error 1.24
Placebo	Magnitude of Greatest Hypoglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12.	Magnitude of excursion, Month 12	11.2 milligrams per deciliter	Standard Error 1.2
Otelixizumab	Magnitude of Greatest Hypoglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12.	Magnitude of excursion, Week 12	10.8 milligrams per deciliter	Standard Error 0.9
Otelixizumab	Magnitude of Greatest Hypoglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12.	Magnitude of excursion, Month 6	10.6 milligrams per deciliter	Standard Error 0.77
Otelixizumab	Magnitude of Greatest Hypoglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12.	Magnitude of excursion, Month 12	11.0 milligrams per deciliter	Standard Error 0.92

Secondary

Mean Daily Insulin Use at Week 12 and Months 6 and 12.

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.

Population: ITT population.

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Placebo	Mean Daily Insulin Use at Week 12 and Months 6 and 12.	Mean daily insulin use at Month 6	0.36 IU/kg	Standard Error 0.022
Placebo	Mean Daily Insulin Use at Week 12 and Months 6 and 12.	Mean daily insulin use at Week 12	0.34 IU/kg	Standard Error 0.017
Placebo	Mean Daily Insulin Use at Week 12 and Months 6 and 12.	Mean daily insulin use at Month 12	0.42 IU/kg	Standard Error 0.023
Otelixizumab	Mean Daily Insulin Use at Week 12 and Months 6 and 12.	Mean daily insulin use at Week 12	0.31 IU/kg	Standard Error 0.013
Otelixizumab	Mean Daily Insulin Use at Week 12 and Months 6 and 12.	Mean daily insulin use at Month 6	0.36 IU/kg	Standard Error 0.016
Otelixizumab	Mean Daily Insulin Use at Week 12 and Months 6 and 12.	Mean daily insulin use at Month 12	0.39 IU/kg	Standard Error 0.017

Comparison: Mean insulin use, Placebo Vs Otelixizumab at Week 12p-value: 0.28195% CI: [-0.07, 0.01]Mixed effects repeated measures model

Comparison: Mean insulin use, Placebo Vs Otelixizumab at Month 6p-value: 0.96995% CI: [-0.05, 0.05]Mixed effects repeated measures model

Comparison: Mean insulin use, Placebo Vs Otelixizumab at Month 12p-value: 0.27295% CI: [-0.08, 0.02]Mixed effects repeated measures model

Secondary

Number of Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12.

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

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

Arm	Measure	Group	Value (MEAN)	Dispersion
Placebo	Number of Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12.	Threshold > 130 mg/dL at Week 12	20.5 Hyperglycemic excursions	Standard Error 1.72
Placebo	Number of Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12.	Threshold > 100 mg/dL at Month 12	35.6 Hyperglycemic excursions	Standard Error 1.97
Placebo	Number of Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12.	Threshold > 100 mg/dL at Week 12	34.0 Hyperglycemic excursions	Standard Error 1.78
Placebo	Number of Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12.	Threshold > 200 mg/dL at Week 12	5.7 Hyperglycemic excursions	Standard Error 0.85
Placebo	Number of Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12.	Threshold > 100 mg/dL at Month 6	33.5 Hyperglycemic excursions	Standard Error 1.77
Placebo	Number of Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12.	Threshold > 130 mg/dL at Month 6	20.8 Hyperglycemic excursions	Standard Error 1.68
Placebo	Number of Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12.	Threshold > 200 mg/dL at Month 6	6.5 Hyperglycemic excursions	Standard Error 1.07
Placebo	Number of Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12.	Threshold > 130 mg/dL at Month 12	24.0 Hyperglycemic excursions	Standard Error 1.92
Placebo	Number of Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12.	Threshold > 200 mg/dL at Month 12	8.6 Hyperglycemic excursions	Standard Error 1.42
Otelixizumab	Number of Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12.	Threshold > 200 mg/dL at Month 12	6.9 Hyperglycemic excursions	Standard Error 0.59
Otelixizumab	Number of Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12.	Threshold > 130 mg/dL at Month 6	22.7 Hyperglycemic excursions	Standard Error 1.25
Otelixizumab	Number of Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12.	Threshold > 130 mg/dL at Month 12	22.2 Hyperglycemic excursions	Standard Error 1.05
Otelixizumab	Number of Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12.	Threshold > 100 mg/dL at Week 12	32.9 Hyperglycemic excursions	Standard Error 1.15
Otelixizumab	Number of Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12.	Threshold > 130 mg/dL at Week 12	19.9 Hyperglycemic excursions	Standard Error 1.01
Otelixizumab	Number of Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12.	Threshold > 200 mg/dL at Month 6	7.9 Hyperglycemic excursions	Standard Error 0.85
Otelixizumab	Number of Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12.	Threshold > 200 mg/dL at Week 12	5.6 Hyperglycemic excursions	Standard Error 0.59
Otelixizumab	Number of Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12.	Threshold > 100 mg/dL at Month 12	33.4 Hyperglycemic excursions	Standard Error 1.27
Otelixizumab	Number of Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12.	Threshold > 100 mg/dL at Month 6	35.1 Hyperglycemic excursions	Standard Error 1.41

Secondary

Number of Hypoglycemic Events Defined by Hypoglycemic Event Categories From Baseline Upto Month 12

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

Population: ITT population.

Arm	Measure	Group	Value (NUMBER)
Placebo	Number of Hypoglycemic Events Defined by Hypoglycemic Event Categories From Baseline Upto Month 12	Severe hypoglycemia upto Month 12	2 Hypoglycemic events
Placebo	Number of Hypoglycemic Events Defined by Hypoglycemic Event Categories From Baseline Upto Month 12	Probable symptomatic hypoglycemia upto Month 12	84 Hypoglycemic events
Placebo	Number of Hypoglycemic Events Defined by Hypoglycemic Event Categories From Baseline Upto Month 12	Documented symptomatic hypoglycemia upto Month 12	3092 Hypoglycemic events
Placebo	Number of Hypoglycemic Events Defined by Hypoglycemic Event Categories From Baseline Upto Month 12	Relative hypoglycemia upto Month 12	85 Hypoglycemic events
Placebo	Number of Hypoglycemic Events Defined by Hypoglycemic Event Categories From Baseline Upto Month 12	Asymptomatic hypoglycemia upto Month 12	4718 Hypoglycemic events
Otelixizumab	Number of Hypoglycemic Events Defined by Hypoglycemic Event Categories From Baseline Upto Month 12	Relative hypoglycemia upto Month 12	211 Hypoglycemic events
Otelixizumab	Number of Hypoglycemic Events Defined by Hypoglycemic Event Categories From Baseline Upto Month 12	Severe hypoglycemia upto Month 12	5 Hypoglycemic events
Otelixizumab	Number of Hypoglycemic Events Defined by Hypoglycemic Event Categories From Baseline Upto Month 12	Asymptomatic hypoglycemia upto Month 12	9962 Hypoglycemic events
Otelixizumab	Number of Hypoglycemic Events Defined by Hypoglycemic Event Categories From Baseline Upto Month 12	Probable symptomatic hypoglycemia upto Month 12	93 Hypoglycemic events
Otelixizumab	Number of Hypoglycemic Events Defined by Hypoglycemic Event Categories From Baseline Upto Month 12	Documented symptomatic hypoglycemia upto Month 12	6322 Hypoglycemic events

Secondary

Number of Hypoglycemic Excursions (<=70 mg/dL) With Most Complete Glucose at Week 12 and Months 6 and 12.

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.

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

Arm	Measure	Group	Value (MEAN)	Dispersion
Placebo	Number of Hypoglycemic Excursions (<=70 mg/dL) With Most Complete Glucose at Week 12 and Months 6 and 12.	Number of hypoglycemic excursions at Week 12	2.3 Hypoglycemic excursions	Standard Error 0.28
Placebo	Number of Hypoglycemic Excursions (<=70 mg/dL) With Most Complete Glucose at Week 12 and Months 6 and 12.	Number of hypoglycemic excursions at Month 6	3.0 Hypoglycemic excursions	Standard Error 0.36
Placebo	Number of Hypoglycemic Excursions (<=70 mg/dL) With Most Complete Glucose at Week 12 and Months 6 and 12.	Number of hypoglycemic excursions at Month 12	2.9 Hypoglycemic excursions	Standard Error 0.41
Otelixizumab	Number of Hypoglycemic Excursions (<=70 mg/dL) With Most Complete Glucose at Week 12 and Months 6 and 12.	Number of hypoglycemic excursions at Month 12	3.2 Hypoglycemic excursions	Standard Error 0.32
Otelixizumab	Number of Hypoglycemic Excursions (<=70 mg/dL) With Most Complete Glucose at Week 12 and Months 6 and 12.	Number of hypoglycemic excursions at Week 12	2.8 Hypoglycemic excursions	Standard Error 0.27
Otelixizumab	Number of Hypoglycemic Excursions (<=70 mg/dL) With Most Complete Glucose at Week 12 and Months 6 and 12.	Number of hypoglycemic excursions at Month 6	2.9 Hypoglycemic excursions	Standard Error 0.27

Secondary

Number of Participants Who Were Responders for (Glycosylated Hemoglobin) HbA1c/Insulin Use Response at Week 12 and Months 6 and 12

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

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

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Placebo	Number of Participants Who Were Responders for (Glycosylated Hemoglobin) HbA1c/Insulin Use Response at Week 12 and Months 6 and 12	Responders at Week 12	45 Participants
Placebo	Number of Participants Who Were Responders for (Glycosylated Hemoglobin) HbA1c/Insulin Use Response at Week 12 and Months 6 and 12	Responders at Month 6	42 Participants
Placebo	Number of Participants Who Were Responders for (Glycosylated Hemoglobin) HbA1c/Insulin Use Response at Week 12 and Months 6 and 12	Responders at Month 12	34 Participants
Otelixizumab	Number of Participants Who Were Responders for (Glycosylated Hemoglobin) HbA1c/Insulin Use Response at Week 12 and Months 6 and 12	Responders at Month 12	56 Participants
Otelixizumab	Number of Participants Who Were Responders for (Glycosylated Hemoglobin) HbA1c/Insulin Use Response at Week 12 and Months 6 and 12	Responders at Week 12	85 Participants
Otelixizumab	Number of Participants Who Were Responders for (Glycosylated Hemoglobin) HbA1c/Insulin Use Response at Week 12 and Months 6 and 12	Responders at Month 6	74 Participants

Comparison: Percentage of responders, Placebo Vs Otelixizumab at Week 12p-value: 0.73795% CI: [0.47, 1.7]Hochberg adjusted

Comparison: Percentage of responders, Placebo Vs Otelixizumab at Month 6p-value: 0.73795% CI: [0.42, 1.39]Hochberg adjusted

Comparison: Percentage of responders, Placebo Vs Otelixizumab at Month 12p-value: 0.48195% CI: [0.45, 1.46]Hochberg adjusted

Secondary

Number of Participants With Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12

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

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

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Placebo	Number of Participants With Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12	Threshold> 130 mg/dL at Month 6	79 Participants
Placebo	Number of Participants With Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12	Threshold> 130 mg/dL at Week 12	90 Participants
Placebo	Number of Participants With Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12	Threshold> 200 mg/dL at Week 12	65 Participants
Placebo	Number of Participants With Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12	Threshold> 100 mg/dL at Month 12	78 Participants
Placebo	Number of Participants With Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12	Threshold> 100 mg/dL at Week 12	90 Participants
Placebo	Number of Participants With Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12	Threshold> 130 mg/dL at Month 12	77 Participants
Placebo	Number of Participants With Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12	Threshold> 100 mg/dL at Month 6	80 Participants
Placebo	Number of Participants With Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12	Threshold> 200 mg/dL at Month 12	60 Participants
Placebo	Number of Participants With Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12	Threshold> 200 mg/dL at Month 6	57 Participants
Otelixizumab	Number of Participants With Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12	Threshold> 200 mg/dL at Month 12	131 Participants
Otelixizumab	Number of Participants With Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12	Threshold> 100 mg/dL at Week 12	177 Participants
Otelixizumab	Number of Participants With Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12	Threshold> 200 mg/dL at Week 12	130 Participants
Otelixizumab	Number of Participants With Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12	Threshold> 100 mg/dL at Month 6	166 Participants
Otelixizumab	Number of Participants With Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12	Threshold> 130 mg/dL at Month 6	166 Participants
Otelixizumab	Number of Participants With Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12	Threshold> 200 mg/dL at Month 6	139 Participants
Otelixizumab	Number of Participants With Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12	Threshold> 100 mg/dL at Month 12	161 Participants
Otelixizumab	Number of Participants With Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12	Threshold> 130 mg/dL at Month 12	160 Participants
Otelixizumab	Number of Participants With Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12	Threshold> 130 mg/dL at Week 12	177 Participants

Secondary

Number of Participants With Hypoglycemic Events Defined by Hypoglycemic Event Categories From Baseline Upto Month 12

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

Population: 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	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Placebo	Number of Participants With Hypoglycemic Events Defined by Hypoglycemic Event Categories From Baseline Upto Month 12	Severe hypoglycemia upto Month 12	2 Participants
Placebo	Number of Participants With Hypoglycemic Events Defined by Hypoglycemic Event Categories From Baseline Upto Month 12	Documented symptomatic hypoglycemia upto Month 12	78 Participants
Placebo	Number of Participants With Hypoglycemic Events Defined by Hypoglycemic Event Categories From Baseline Upto Month 12	Asymptomatic hypoglycemia upto Month 12	10 Participants
Otelixizumab	Number of Participants With Hypoglycemic Events Defined by Hypoglycemic Event Categories From Baseline Upto Month 12	Severe hypoglycemia upto Month 12	4 Participants
Otelixizumab	Number of Participants With Hypoglycemic Events Defined by Hypoglycemic Event Categories From Baseline Upto Month 12	Documented symptomatic hypoglycemia upto Month 12	163 Participants
Otelixizumab	Number of Participants With Hypoglycemic Events Defined by Hypoglycemic Event Categories From Baseline Upto Month 12	Asymptomatic hypoglycemia upto Month 12	13 Participants

Secondary

Number of Participants With Hypoglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12

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

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

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Placebo	Number of Participants With Hypoglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12	Percentage of participants with excursion,Month 6	57 Participants
Placebo	Number of Participants With Hypoglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12	Percentage of participants with excursion,Week 12	72 Participants
Placebo	Number of Participants With Hypoglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12	Percentage of participants with excursion,Month 12	56 Participants
Otelixizumab	Number of Participants With Hypoglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12	Percentage of participants with excursion,Week 12	127 Participants
Otelixizumab	Number of Participants With Hypoglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12	Percentage of participants with excursion,Month 6	121 Participants
Otelixizumab	Number of Participants With Hypoglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12	Percentage of participants with excursion,Month 12	111 Participants

Secondary

Percent Change From Baseline in CD3/TCR Modulation on CD4+ T Cells and CD8+ T Cells at Day 1, Day 4, Day 8

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

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

Arm	Measure	Group	Value (MEAN)	Dispersion
Placebo	Percent Change From Baseline in CD3/TCR Modulation on CD4+ T Cells and CD8+ T Cells at Day 1, Day 4, Day 8	CD4+ T cells, Day 4, 2 hours after EOI	103.8 Percent change	Standard Error 8.93
Placebo	Percent Change From Baseline in CD3/TCR Modulation on CD4+ T Cells and CD8+ T Cells at Day 1, Day 4, Day 8	CD8+ T cells, Day 1, 2 hours after EOI	95.2 Percent change	Standard Error 2.72
Placebo	Percent Change From Baseline in CD3/TCR Modulation on CD4+ T Cells and CD8+ T Cells at Day 1, Day 4, Day 8	CD4+ T cells, Day 8, pre-dose	101.4 Percent change	Standard Error 6.09
Placebo	Percent Change From Baseline in CD3/TCR Modulation on CD4+ T Cells and CD8+ T Cells at Day 1, Day 4, Day 8	CD8+ T cells, Day 4, 2 hours after EOI	111.1 Percent change	Standard Error 10.56
Placebo	Percent Change From Baseline in CD3/TCR Modulation on CD4+ T Cells and CD8+ T Cells at Day 1, Day 4, Day 8	CD8+ T cells, Day 8, 2 hours after EOI	103.0 Percent change	Standard Error 6.05
Placebo	Percent Change From Baseline in CD3/TCR Modulation on CD4+ T Cells and CD8+ T Cells at Day 1, Day 4, Day 8	CD8+ T cells, Day 8, pre-dose	101.8 Percent change	Standard Error 6.19
Placebo	Percent Change From Baseline in CD3/TCR Modulation on CD4+ T Cells and CD8+ T Cells at Day 1, Day 4, Day 8	CD4+ T cells, Day 8, 2 hours after EOI	103.4 Percent change	Standard Error 5.87
Placebo	Percent Change From Baseline in CD3/TCR Modulation on CD4+ T Cells and CD8+ T Cells at Day 1, Day 4, Day 8	CD4+ T cells, Day 1, 2 hours after EOI	94.2 Percent change	Standard Error 2.95
Otelixizumab	Percent Change From Baseline in CD3/TCR Modulation on CD4+ T Cells and CD8+ T Cells at Day 1, Day 4, Day 8	CD8+ T cells, Day 8, 2 hours after EOI	36.2 Percent change	Standard Error 2.52
Otelixizumab	Percent Change From Baseline in CD3/TCR Modulation on CD4+ T Cells and CD8+ T Cells at Day 1, Day 4, Day 8	CD4+ T cells, Day 4, 2 hours after EOI	70.8 Percent change	Standard Error 3.89
Otelixizumab	Percent Change From Baseline in CD3/TCR Modulation on CD4+ T Cells and CD8+ T Cells at Day 1, Day 4, Day 8	CD4+ T cells, Day 1, 2 hours after EOI	91.1 Percent change	Standard Error 2.9
Otelixizumab	Percent Change From Baseline in CD3/TCR Modulation on CD4+ T Cells and CD8+ T Cells at Day 1, Day 4, Day 8	CD4+ T cells, Day 8, pre-dose	61.0 Percent change	Standard Error 2.65
Otelixizumab	Percent Change From Baseline in CD3/TCR Modulation on CD4+ T Cells and CD8+ T Cells at Day 1, Day 4, Day 8	CD4+ T cells, Day 8, 2 hours after EOI	32.2 Percent change	Standard Error 2.52
Otelixizumab	Percent Change From Baseline in CD3/TCR Modulation on CD4+ T Cells and CD8+ T Cells at Day 1, Day 4, Day 8	CD8+ T cells, Day 1, 2 hours after EOI	93.7 Percent change	Standard Error 3.06
Otelixizumab	Percent Change From Baseline in CD3/TCR Modulation on CD4+ T Cells and CD8+ T Cells at Day 1, Day 4, Day 8	CD8+ T cells, Day 4, 2 hours after EOI	77.1 Percent change	Standard Error 4.33
Otelixizumab	Percent Change From Baseline in CD3/TCR Modulation on CD4+ T Cells and CD8+ T Cells at Day 1, Day 4, Day 8	CD8+ T cells, Day 8, pre-dose	62.3 Percent change	Standard Error 2.68

Secondary

Percent Change From Baseline in CD3/TCR Saturation on CD4+ T Cells and CD8+ T Cells at Day 1, Day 4, Day 8

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

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

Arm	Measure	Group	Value (MEAN)	Dispersion
Placebo	Percent Change From Baseline in CD3/TCR Saturation on CD4+ T Cells and CD8+ T Cells at Day 1, Day 4, Day 8	CD8+ T cells, Day 1, 2 hours after EOI	92.4 Percent change	Standard Error 2.38
Placebo	Percent Change From Baseline in CD3/TCR Saturation on CD4+ T Cells and CD8+ T Cells at Day 1, Day 4, Day 8	CD4+ T cells, Day 8, pre-dose	97.7 Percent change	Standard Error 10.66
Placebo	Percent Change From Baseline in CD3/TCR Saturation on CD4+ T Cells and CD8+ T Cells at Day 1, Day 4, Day 8	CD8+ T cells, Day 4, 2 hours after EOI	116.7 Percent change	Standard Error 14.53
Placebo	Percent Change From Baseline in CD3/TCR Saturation on CD4+ T Cells and CD8+ T Cells at Day 1, Day 4, Day 8	CD4+ T cells, Day 1, 2 hours after EOI	93.4 Percent change	Standard Error 2.4
Placebo	Percent Change From Baseline in CD3/TCR Saturation on CD4+ T Cells and CD8+ T Cells at Day 1, Day 4, Day 8	CD8+ T cells, Day 8, pre-dose	97.4 Percent change	Standard Error 11.84
Placebo	Percent Change From Baseline in CD3/TCR Saturation on CD4+ T Cells and CD8+ T Cells at Day 1, Day 4, Day 8	CD4+ T cells, Day 8, 2 hours after EOI	98.0 Percent change	Standard Error 13.03
Placebo	Percent Change From Baseline in CD3/TCR Saturation on CD4+ T Cells and CD8+ T Cells at Day 1, Day 4, Day 8	CD8+ T cells, Day 8, 2 hours after EOI	98.2 Percent change	Standard Error 14.63
Placebo	Percent Change From Baseline in CD3/TCR Saturation on CD4+ T Cells and CD8+ T Cells at Day 1, Day 4, Day 8	CD4+ T cells, Day 4, 2 hours after EOI	109.7 Percent change	Standard Error 11.91
Otelixizumab	Percent Change From Baseline in CD3/TCR Saturation on CD4+ T Cells and CD8+ T Cells at Day 1, Day 4, Day 8	CD8+ T cells, Day 8, 2 hours after EOI	23.0 Percent change	Standard Error 3.72
Otelixizumab	Percent Change From Baseline in CD3/TCR Saturation on CD4+ T Cells and CD8+ T Cells at Day 1, Day 4, Day 8	CD4+ T cells, Day 4, 2 hours after EOI	50.2 Percent change	Standard Error 4.9
Otelixizumab	Percent Change From Baseline in CD3/TCR Saturation on CD4+ T Cells and CD8+ T Cells at Day 1, Day 4, Day 8	CD4+ T cells, Day 8, pre-dose	59.0 Percent change	Standard Error 5.31
Otelixizumab	Percent Change From Baseline in CD3/TCR Saturation on CD4+ T Cells and CD8+ T Cells at Day 1, Day 4, Day 8	CD4+ T cells, Day 8, 2 hours after EOI	21.7 Percent change	Standard Error 3.33
Otelixizumab	Percent Change From Baseline in CD3/TCR Saturation on CD4+ T Cells and CD8+ T Cells at Day 1, Day 4, Day 8	CD8+ T cells, Day 1, 2 hours after EOI	91.4 Percent change	Standard Error 3.82
Otelixizumab	Percent Change From Baseline in CD3/TCR Saturation on CD4+ T Cells and CD8+ T Cells at Day 1, Day 4, Day 8	CD8+ T cells, Day 4, 2 hours after EOI	51.6 Percent change	Standard Error 5.23
Otelixizumab	Percent Change From Baseline in CD3/TCR Saturation on CD4+ T Cells and CD8+ T Cells at Day 1, Day 4, Day 8	CD8+ T cells, Day 8, pre-dose	60.8 Percent change	Standard Error 6.11
Otelixizumab	Percent Change From Baseline in CD3/TCR Saturation on CD4+ T Cells and CD8+ T Cells at Day 1, Day 4, Day 8	CD4+ T cells, Day 1, 2 hours after EOI	90.9 Percent change	Standard Error 3.82

Secondary

Percent Change From Baseline in Cell-bound Otelixizumab on CD4+ T Cells at Day 1, Day 4, Day 8

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

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

Arm	Measure	Group	Value (MEAN)	Dispersion
Placebo	Percent Change From Baseline in Cell-bound Otelixizumab on CD4+ T Cells at Day 1, Day 4, Day 8	CD4+ T cells, Day 1, 2 hours after EOI	125.1 Percent change	Standard Error 18
Placebo	Percent Change From Baseline in Cell-bound Otelixizumab on CD4+ T Cells at Day 1, Day 4, Day 8	CD4+ T cells, Day 4, 2 hours after EOI	174.3 Percent change	Standard Error 41.95
Placebo	Percent Change From Baseline in Cell-bound Otelixizumab on CD4+ T Cells at Day 1, Day 4, Day 8	CD4+ T cells, Day 8, pre-dose	151.5 Percent change	Standard Error 39.49
Placebo	Percent Change From Baseline in Cell-bound Otelixizumab on CD4+ T Cells at Day 1, Day 4, Day 8	CD4+ T cells, Day 8, 2 hours after EOI	167.9 Percent change	Standard Error 47.67
Otelixizumab	Percent Change From Baseline in Cell-bound Otelixizumab on CD4+ T Cells at Day 1, Day 4, Day 8	CD4+ T cells, Day 8, 2 hours after EOI	1387.5 Percent change	Standard Error 274.21
Otelixizumab	Percent Change From Baseline in Cell-bound Otelixizumab on CD4+ T Cells at Day 1, Day 4, Day 8	CD4+ T cells, Day 1, 2 hours after EOI	914.8 Percent change	Standard Error 269.18
Otelixizumab	Percent Change From Baseline in Cell-bound Otelixizumab on CD4+ T Cells at Day 1, Day 4, Day 8	CD4+ T cells, Day 8, pre-dose	471.5 Percent change	Standard Error 98.53
Otelixizumab	Percent Change From Baseline in Cell-bound Otelixizumab on CD4+ T Cells at Day 1, Day 4, Day 8	CD4+ T cells, Day 4, 2 hours after EOI	2719.8 Percent change	Standard Error 369.41

Secondary

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

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

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

Arm	Measure	Group	Value (MEDIAN)
Placebo	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	CD4+CD25+FoxP3+ T, Day 4, 2 hours after EOI	118.8 Percent change
Placebo	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	CD4+CD25+FoxP3+ T, Week 10	109.9 Percent change
Placebo	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	CD4+CD25+FoxP3+ T, Month 6	137.9 Percent change
Placebo	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	CD4+CD25hiFoxP3+ T Cells, Day 4, 2 hours after EOI	151.9 Percent change
Placebo	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	CD4+CD25hiFoxP3+ T Cells, Day 21	110.0 Percent change
Placebo	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	CD4+CD25+FoxP3+ T, Day 8 pre-dose	94.4 Percent change
Placebo	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	CD4+CD25+FoxP3+ T, Day 8, 2 hours after EOI	113.2 Percent change
Placebo	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	CD4+CD25+FoxP3+ T, Day 14	114.5 Percent change
Placebo	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	CD4+CD25+FoxP3+ T, Day 21	114.6 Percent change
Placebo	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	CD4+CD25+FoxP3+ T, Day 28	95.1 Percent change
Placebo	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	CD4+CD25+FoxP3+ T, Week 6	104.1 Percent change
Placebo	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	CD4+CD25+FoxP3+ T, Week 8	110.1 Percent change
Placebo	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	CD4+CD25+FoxP3+ T, Week 12	102.5 Percent change
Placebo	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	CD4+CD25+FoxP3+ T, Month 12	122.0 Percent change
Placebo	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	CD4+CD25hiFoxP3+ T Cells, Day 8 pre-dose	93.8 Percent change
Placebo	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	CD4+CD25hiFoxP3+ T Cells, Day 8, 2 hours after EOI	110.7 Percent change
Placebo	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	CD4+CD25hiFoxP3+ T Cells, Day 14	118.4 Percent change
Placebo	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	CD4+CD25hiFoxP3+ T Cells, Day 28	101.1 Percent change
Placebo	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	CD4+CD25hiFoxP3+ T Cells, Week 6	106.9 Percent change
Placebo	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	CD4+CD25hiFoxP3+ T Cells, Week 8	131.7 Percent change
Placebo	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	CD4+CD25hiFoxP3+ T Cells, Week 10	97.7 Percent change
Placebo	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	CD4+CD25hiFoxP3+ T Cells, Week 12	113.6 Percent change
Placebo	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	CD4+CD25hiFoxP3+ T Cells, Month 6	150.9 Percent change
Placebo	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	CD4+CD25hiFoxP3+ T Cells, Month 12	166.4 Percent change
Otelixizumab	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	CD4+CD25+FoxP3+ T, Month 6	133.3 Percent change
Otelixizumab	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	CD4+CD25+FoxP3+ T, Day 4, 2 hours after EOI	53.4 Percent change
Otelixizumab	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	CD4+CD25+FoxP3+ T, Week 8	107.1 Percent change
Otelixizumab	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	CD4+CD25hiFoxP3+ T Cells, Week 6	110.7 Percent change
Otelixizumab	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	CD4+CD25+FoxP3+ T, Month 12	106.9 Percent change
Otelixizumab	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	CD4+CD25hiFoxP3+ T Cells, Day 4, 2 hours after EOI	60.8 Percent change
Otelixizumab	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	CD4+CD25hiFoxP3+ T Cells, Day 8, 2 hours after EOI	35.9 Percent change
Otelixizumab	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	CD4+CD25hiFoxP3+ T Cells, Week 12	90.9 Percent change
Otelixizumab	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	CD4+CD25hiFoxP3+ T Cells, Day 8 pre-dose	43.5 Percent change
Otelixizumab	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	CD4+CD25+FoxP3+ T, Day 8 pre-dose	49.7 Percent change
Otelixizumab	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	CD4+CD25hiFoxP3+ T Cells, Week 8	120.3 Percent change
Otelixizumab	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	CD4+CD25+FoxP3+ T, Day 8, 2 hours after EOI	40.1 Percent change
Otelixizumab	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	CD4+CD25hiFoxP3+ T Cells, Month 12	160.6 Percent change
Otelixizumab	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	CD4+CD25+FoxP3+ T, Day 14	101.3 Percent change
Otelixizumab	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	CD4+CD25hiFoxP3+ T Cells, Day 14	109.7 Percent change
Otelixizumab	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	CD4+CD25+FoxP3+ T, Day 21	101.9 Percent change
Otelixizumab	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	CD4+CD25hiFoxP3+ T Cells, Day 21	98.8 Percent change
Otelixizumab	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	CD4+CD25+FoxP3+ T, Day 28	101.7 Percent change
Otelixizumab	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	CD4+CD25hiFoxP3+ T Cells, Week 10	107.0 Percent change
Otelixizumab	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	CD4+CD25+FoxP3+ T, Week 6	106.6 Percent change
Otelixizumab	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	CD4+CD25hiFoxP3+ T Cells, Day 28	108.7 Percent change
Otelixizumab	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	CD4+CD25+FoxP3+ T, Week 10	102.7 Percent change
Otelixizumab	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	CD4+CD25hiFoxP3+ T Cells, Month 6	153.2 Percent change
Otelixizumab	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	CD4+CD25+FoxP3+ T, Week 12	85.5 Percent change

Source: ClinicalTrials.gov · Data processed: Mar 20, 2026

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

Conditions

Keywords

Brief summary

Detailed description

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Recruitment details

Pre-assignment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Change From Baseline in 2-hour Mixed Meal Stimulated C-peptide Area Under Curve [AUC] (Normalized for 120-minute Time Interval) at Month 12

Change From Baseline in Average Daily Risk Range (ADRR) at Week 12 and Months 6 and 12.

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

Composite Rank Summary for C-Peptide AUC, HbA1c and Exogenous Insulin Use at Month 6 and Month 12

Composite Rank Summary for HbA1c and Exogenous Insulin Use at Month 6 and Month 12

HbA1c Level at Week 12 and Months 6 and 12

Magnitude of Greatest Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12.

Magnitude of Greatest Hypoglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12.

Mean Daily Insulin Use at Week 12 and Months 6 and 12.

Number of Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12.

Number of Hypoglycemic Events Defined by Hypoglycemic Event Categories From Baseline Upto Month 12

Number of Hypoglycemic Excursions (<=70 mg/dL) With Most Complete Glucose at Week 12 and Months 6 and 12.

Number of Participants Who Were Responders for (Glycosylated Hemoglobin) HbA1c/Insulin Use Response at Week 12 and Months 6 and 12

Number of Participants With Hyperglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12

Number of Participants With Hypoglycemic Events Defined by Hypoglycemic Event Categories From Baseline Upto Month 12

Number of Participants With Hypoglycemic Excursions With Most Complete Glucose at Week 12 and Months 6 and 12

Percent Change From Baseline in CD3/TCR Modulation on CD4+ T Cells and CD8+ T Cells at Day 1, Day 4, Day 8

Percent Change From Baseline in CD3/TCR Saturation on CD4+ T Cells and CD8+ T Cells at Day 1, Day 4, Day 8

Percent Change From Baseline in Cell-bound Otelixizumab on CD4+ T Cells at Day 1, Day 4, Day 8

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