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

Primary Purpose

Diabetes Mellitus, Type 1

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

otelixizumab infusion plus physician determined standard of care

placebo infusion plus physician determined standard of care

About this trial

This is an interventional treatment trial for Diabetes Mellitus, Type 1 focused on measuring Type 1 diabetes, new onset type 1 diabetes, T1DM, Type l diabetes, juvenile diabetes

Eligibility Criteria

12 Years - 45 Years (Child, Adult)All SexesDoes not accept 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

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

otelixizumab

placebo

Arm Description

otelixizumab

Placebo

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Full Information

NCT ID

NCT00678886

First Posted

May 13, 2008

Last Updated

September 5, 2017

Sponsor

GlaxoSmithKline

Collaborators

Juvenile Diabetes Research Foundation

1. Study Identification

Unique Protocol Identification Number

NCT00678886

Brief Title

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

Acronym

DEFEND-1

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2017

Overall Recruitment Status

Completed

Study Start Date

July 29, 2008 (Actual)

Primary Completion Date

January 31, 2012 (Actual)

Study Completion Date

January 31, 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

GlaxoSmithKline

Collaborators

Juvenile Diabetes Research Foundation

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Diabetes Mellitus, Type 1

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

272 (Actual)

8. Arms, Groups, and Interventions

Arm Title

otelixizumab

Arm Type

Experimental

Arm Description

otelixizumab

Arm Title

placebo

Arm Type

Placebo Comparator

Arm Description

Placebo

Intervention Type

Biological

Intervention Name(s)

otelixizumab infusion plus physician determined standard of care

Other Intervention Name(s)

monoclonal antibody, ChAglyCD3, anti-CD3, TRX4

Intervention Description

infusion

Intervention Type

Biological

Intervention Name(s)

placebo infusion plus physician determined standard of care

Intervention Description

infusion

Primary Outcome Measure Information:

Title

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

Description

Time Frame

Baseline (0-120 minutes on Day 1) and Month 12 (0-120 minutes)

Secondary Outcome Measure Information:

Title

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

Description

Time Frame

Week 12 and Months 6 and 12

Title

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

Description

Time Frame

Week 12 and Months 6 and 12.

Title

HbA1c Level at Week 12 and Months 6 and 12

Description

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

Time Frame

Week 12 and Months 6 and 12

Title

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

Description

Time Frame

Upto Month 12

Title

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

Description

Time Frame

Upto Month 12

Title

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

Description

Time Frame

Week 12 and Months 6 and 12.

Title

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

Description

Time Frame

Week 12 and Months 6 and 12.

Title

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

Description

Time Frame

Week 12 and Months 6 and 12

Title

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

Description

Time Frame

Week 12 and Months 6 and 12

Title

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

Description

Time Frame

Week 12 and Months 6 and 12.

Title

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

Description

Time Frame

Week 12 and Months 6 and 12

Title

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

Description

Time Frame

Baseline (Day 1) and Week 12, Months 6 and 12.

Title

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

Description

Time Frame

Month 6 and 12

Title

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

Description

Time Frame

Month 6 and 12

Title

Change From Baseline in Level of Cytokines Interleukin (IL-6), IL-10 and Tumor Necrosis Factor-alpha (TNF-a) at Day 1, Day 4, Day 8

Description

Time Frame

Day 1, Day 4, Day 8

Title

Percent Change From Baseline in Circulating Peripheral Lymphocytes CD4+CD25+FoxP3+ T Cells and CD4+CD25hiFoxP3+ T Cells in Type 1 Diabetes Mellitus (TIDM) up to Month 12

Description

Time Frame

Baseline (pre-dose on Day 1) and up to 12 Months

Title

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

Description

Time Frame

Baseline (pre-dose on Day 1), Day 4 and Day 8

Title

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

Description

Time Frame

Baseline (Pre-dose Day 1), Day 4, Day 8

Title

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

Description

Time Frame

Baseline (Pre-dose Day 1), Day 4, Day 8

10. Eligibility

Sex

All

Minimum Age & Unit of Time

12 Years

Maximum Age & Unit of Time

45 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

GSK Clinical Trials

Organizational Affiliation

GlaxoSmithKline

Official's Role

Study Director

Facility Information:

Facility Name

GSK Investigational Site

City

Birmingham

State/Province

Alabama

ZIP/Postal Code

35294

Country

United States

Facility Name

GSK Investigational Site

City

Little Rock

State/Province

Arkansas

ZIP/Postal Code

72205

Country

United States

Facility Name

GSK Investigational Site

City

Costa Mesa

State/Province

California

ZIP/Postal Code

92626

Country

United States

Facility Name

GSK Investigational Site

City

Los Angeles

State/Province

California

ZIP/Postal Code

90033

Country

United States

Facility Name

GSK Investigational Site

City

Orange

State/Province

California

ZIP/Postal Code

92868

Country

United States

Facility Name

GSK Investigational Site

City

Riverside

State/Province

California

ZIP/Postal Code

92506

Country

United States

Facility Name

GSK Investigational Site

City

Santa Ana

State/Province

California

ZIP/Postal Code

92705

Country

United States

Facility Name

GSK Investigational Site

City

Torrance

State/Province

California

ZIP/Postal Code

90502

Country

United States

Facility Name

GSK Investigational Site

City

Walnut Creek

State/Province

California

ZIP/Postal Code

94598

Country

United States

Facility Name

GSK Investigational Site

City

Aurora

State/Province

Colorado

ZIP/Postal Code

80045

Country

United States

Facility Name

GSK Investigational Site

City

Washington, D.C.

State/Province

District of Columbia

ZIP/Postal Code

20037

Country

United States

Facility Name

GSK Investigational Site

City

Boca Raton

State/Province

Florida

ZIP/Postal Code

33486

Country

United States

Facility Name

GSK Investigational Site

City

Jupiter

State/Province

Florida

ZIP/Postal Code

33458

Country

United States

Facility Name

GSK Investigational Site

City

Miami

State/Province

Florida

ZIP/Postal Code

33136

Country

United States

Facility Name

GSK Investigational Site

City

Miami

State/Province

Florida

ZIP/Postal Code

33169

Country

United States

Facility Name

GSK Investigational Site

City

Orlando

State/Province

Florida

ZIP/Postal Code

32803

Country

United States

Facility Name

GSK Investigational Site

City

Orlando

State/Province

Florida

ZIP/Postal Code

32835

Country

United States

Facility Name

GSK Investigational Site

City

Pembroke Pines

State/Province

Florida

ZIP/Postal Code

33024

Country

United States

Facility Name

GSK Investigational Site

City

Trinity

State/Province

Florida

ZIP/Postal Code

34655

Country

United States

Facility Name

GSK Investigational Site

City

Winter Park

State/Province

Florida

ZIP/Postal Code

32789

Country

United States

Facility Name

GSK Investigational Site

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30309

Country

United States

Facility Name

GSK Investigational Site

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30342

Country

United States

Facility Name

GSK Investigational Site

City

Honolulu

State/Province

Hawaii

ZIP/Postal Code

96813

Country

United States

Facility Name

GSK Investigational Site

City

Boise

State/Province

Idaho

ZIP/Postal Code

83702

Country

United States

Facility Name

GSK Investigational Site

City

Idaho Falls

State/Province

Idaho

ZIP/Postal Code

83404-7542

Country

United States

Facility Name

GSK Investigational Site

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60612

Country

United States

Facility Name

GSK Investigational Site

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60637

Country

United States

Facility Name

GSK Investigational Site

City

Indianapolis

State/Province

Indiana

ZIP/Postal Code

46260

Country

United States

Facility Name

GSK Investigational Site

City

Baltimore

State/Province

Kansas

ZIP/Postal Code

21287

Country

United States

Facility Name

GSK Investigational Site

City

Topeka

State/Province

Kansas

ZIP/Postal Code

66606

Country

United States

Facility Name

GSK Investigational Site

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21201

Country

United States

Facility Name

GSK Investigational Site

City

Worcester

State/Province

Massachusetts

ZIP/Postal Code

01655-0002

Country

United States

Facility Name

GSK Investigational Site

City

Detroit

State/Province

Michigan

ZIP/Postal Code

48201

Country

United States

Facility Name

GSK Investigational Site

City

Kalamazoo

State/Province

Michigan

ZIP/Postal Code

49048

Country

United States

Facility Name

GSK Investigational Site

City

Gulfport

State/Province

Mississippi

ZIP/Postal Code

39501

Country

United States

Facility Name

GSK Investigational Site

City

Columbia

State/Province

Missouri

ZIP/Postal Code

65212

Country

United States

Facility Name

GSK Investigational Site

City

Kansas City

State/Province

Missouri

ZIP/Postal Code

64106

Country

United States

Facility Name

GSK Investigational Site

City

Saint Louis

State/Province

Missouri

ZIP/Postal Code

63110

Country

United States

Facility Name

GSK Investigational Site

City

Omaha

State/Province

Nebraska

ZIP/Postal Code

68131

Country

United States

Facility Name

GSK Investigational Site

City

Neptune City

State/Province

New Jersey

ZIP/Postal Code

07753

Country

United States

Facility Name

GSK Investigational Site

City

Buffalo

State/Province

New York

ZIP/Postal Code

14209

Country

United States

Facility Name

GSK Investigational Site

City

Mineola

State/Province

New York

ZIP/Postal Code

11501

Country

United States

Facility Name

GSK Investigational Site

City

New York

State/Province

New York

ZIP/Postal Code

10032

Country

United States

Facility Name

GSK Investigational Site

City

Rochester

State/Province

New York

ZIP/Postal Code

14642

Country

United States

Facility Name

GSK Investigational Site

City

Durham

State/Province

North Carolina

ZIP/Postal Code

27713

Country

United States

Facility Name

GSK Investigational Site

City

Columbus

State/Province

Ohio

ZIP/Postal Code

43205

Country

United States

Facility Name

GSK Investigational Site

City

Columbus

State/Province

Ohio

ZIP/Postal Code

43210

Country

United States

Facility Name

GSK Investigational Site

City

Dayton

State/Province

Ohio

ZIP/Postal Code

45415-2560

Country

United States

Facility Name

GSK Investigational Site

City

Mentor

State/Province

Ohio

ZIP/Postal Code

44060

Country

United States

Facility Name

GSK Investigational Site

City

Tulsa

State/Province

Oklahoma

ZIP/Postal Code

74136-8303

Country

United States

Facility Name

GSK Investigational Site

City

Eugene

State/Province

Oregon

ZIP/Postal Code

97401

Country

United States

Facility Name

GSK Investigational Site

City

Portland

State/Province

Oregon

ZIP/Postal Code

97210

Country

United States

Facility Name

GSK Investigational Site

City

Langhorne

State/Province

Pennsylvania

ZIP/Postal Code

19047

Country

United States

Facility Name

GSK Investigational Site

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19140

Country

United States

Facility Name

GSK Investigational Site

City

Charleston

State/Province

South Carolina

ZIP/Postal Code

29425-6240

Country

United States

Facility Name

GSK Investigational Site

City

Rapid City

State/Province

South Dakota

ZIP/Postal Code

57701

Country

United States

Facility Name

GSK Investigational Site

City

Chattanooga

State/Province

Tennessee

ZIP/Postal Code

37403

Country

United States

Facility Name

GSK Investigational Site

City

Memphis

State/Province

Tennessee

ZIP/Postal Code

38119

Country

United States

Facility Name

GSK Investigational Site

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37212

Country

United States

Facility Name

GSK Investigational Site

City

Dallas

State/Province

Texas

ZIP/Postal Code

75231

Country

United States

Facility Name

GSK Investigational Site

City

Dallas

State/Province

Texas

ZIP/Postal Code

75390

Country

United States

Facility Name

GSK Investigational Site

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

Facility Name

GSK Investigational Site

City

Hurst

State/Province

Texas

ZIP/Postal Code

76054

Country

United States

Facility Name

GSK Investigational Site

City

San Antonio

State/Province

Texas

ZIP/Postal Code

78229

Country

United States

Facility Name

GSK Investigational Site

City

Schertz

State/Province

Texas

ZIP/Postal Code

782154

Country

United States

Facility Name

GSK Investigational Site

City

Ogden

State/Province

Utah

ZIP/Postal Code

84403

Country

United States

Facility Name

GSK Investigational Site

City

Tacoma

State/Province

Washington

ZIP/Postal Code

98405

Country

United States

Facility Name

GSK Investigational Site

City

Calgary

State/Province

Alberta

ZIP/Postal Code

T2H 2G4

Country

Canada

Facility Name

GSK Investigational Site

City

Oakville

State/Province

Ontario

ZIP/Postal Code

L6H 3P1

Country

Canada

Facility Name

GSK Investigational Site

City

Smiths Falls

State/Province

Ontario

ZIP/Postal Code

K7A 4W8

Country

Canada

Facility Name

GSK Investigational Site

City

Toronto

State/Province

Ontario

ZIP/Postal Code

M4G 3E8

Country

Canada

Facility Name

GSK Investigational Site

City

Montreal

State/Province

Quebec

ZIP/Postal Code

H2W 1T8

Country

Canada

Facility Name

GSK Investigational Site

City

Pointe-Claire

State/Province

Quebec

ZIP/Postal Code

H9R 3J1

Country

Canada

Facility Name

GSK Investigational Site

City

Arhus C

ZIP/Postal Code

8000

Country

Denmark

Facility Name

GSK Investigational Site

City

Tampere

ZIP/Postal Code

33520

Country

Finland

Facility Name

GSK Investigational Site

City

Turku

ZIP/Postal Code

20520

Country

Finland

Facility Name

GSK Investigational Site

City

Heidelberg

State/Province

Baden-Wuerttemberg

ZIP/Postal Code

69120

Country

Germany

Facility Name

GSK Investigational Site

City

Bad Nauheim

State/Province

Hessen

ZIP/Postal Code

61231

Country

Germany

Facility Name

GSK Investigational Site

City

Bad Lauterberg

State/Province

Niedersachsen

ZIP/Postal Code

37431

Country

Germany

Facility Name

GSK Investigational Site

City

Berlin

ZIP/Postal Code

12200

Country

Germany

Facility Name

GSK Investigational Site

City

Latina

State/Province

Lazio

ZIP/Postal Code

04100

Country

Italy

Facility Name

GSK Investigational Site

City

Roma

State/Province

Lazio

ZIP/Postal Code

00157

Country

Italy

Facility Name

GSK Investigational Site

City

Roma

State/Province

Lazio

ZIP/Postal Code

00161

Country

Italy

Facility Name

GSK Investigational Site

City

Roma

State/Province

Lazio

ZIP/Postal Code

00168

Country

Italy

Facility Name

GSK Investigational Site

City

Monserrato

State/Province

Sardegna

ZIP/Postal Code

09042

Country

Italy

Facility Name

GSK Investigational Site

City

Palermo

State/Province

Sicilia

ZIP/Postal Code

90127

Country

Italy

Facility Name

GSK Investigational Site

City

Milano

ZIP/Postal Code

20132

Country

Italy

Facility Name

GSK Investigational Site

City

Roma

ZIP/Postal Code

00128

Country

Italy

Facility Name

GSK Investigational Site

City

Barcelona

ZIP/Postal Code

8035

Country

Spain

Facility Name

GSK Investigational Site

City

Gerona

Country

Spain

Facility Name

GSK Investigational Site

City

Madrid

ZIP/Postal Code

28040

Country

Spain

Facility Name

GSK Investigational Site

City

Sant Joan

ZIP/Postal Code

´03550

Country

Spain

Facility Name

GSK Investigational Site

City

Tarrasa, Barcelona

ZIP/Postal Code

08221

Country

Spain

Facility Name

GSK Investigational Site

City

Göteborg

ZIP/Postal Code

SE-413 45

Country

Sweden

Facility Name

GSK Investigational Site

City

Halmstad

ZIP/Postal Code

SE-301 85

Country

Sweden

Facility Name

GSK Investigational Site

City

Harnosand

ZIP/Postal Code

871 82

Country

Sweden

Facility Name

GSK Investigational Site

City

Karlskrona

ZIP/Postal Code

SE- 371 85

Country

Sweden

Facility Name

GSK Investigational Site

City

Karlstad

ZIP/Postal Code

SE-651 85

Country

Sweden

Facility Name

GSK Investigational Site

City

Kristianstad

ZIP/Postal Code

291 85

Country

Sweden

Facility Name

GSK Investigational Site

City

Motala

ZIP/Postal Code

SE-591 85

Country

Sweden

Facility Name

GSK Investigational Site

City

Stockholm

ZIP/Postal Code

SE-171 76

Country

Sweden

Facility Name

GSK Investigational Site

City

Umeå

ZIP/Postal Code

SE-901 85

Country

Sweden

Facility Name

GSK Investigational Site

City

Växjö

ZIP/Postal Code

SE-351 85

Country

Sweden

Facility Name

GSK Investigational Site

City

Bath

State/Province

Somerset

ZIP/Postal Code

BA1 3NG

Country

United Kingdom

Facility Name

GSK Investigational Site

City

Blackburn

ZIP/Postal Code

BB2 3HH

Country

United Kingdom

Facility Name

GSK Investigational Site

City

Bristol

ZIP/Postal Code

BS2 8HW

Country

United Kingdom

Facility Name

GSK Investigational Site

City

Hull

ZIP/Postal Code

HU3 2RW

Country

United Kingdom

Facility Name

GSK Investigational Site

City

London

ZIP/Postal Code

SE1 9RT

Country

United Kingdom

Facility Name

GSK Investigational Site

City

Newcastle upon Tyne

ZIP/Postal Code

NE1 4LP

Country

United Kingdom

12. IPD Sharing Statement

Citations:

PubMed Identifier

15972866

Citation

Keymeulen B, Vandemeulebroucke E, Ziegler AG, Mathieu C, Kaufman L, Hale G, Gorus F, Goldman M, Walter M, Candon S, Schandene L, Crenier L, De Block C, Seigneurin JM, De Pauw P, Pierard D, Weets I, Rebello P, Bird P, Berrie E, Frewin M, Waldmann H, Bach JF, Pipeleers D, Chatenoud L. Insulin needs after CD3-antibody therapy in new-onset type 1 diabetes. N Engl J Med. 2005 Jun 23;352(25):2598-608. doi: 10.1056/NEJMoa043980.

Results Reference

background

PubMed Identifier

19111162

Citation

You S, Candon S, Kuhn C, Bach JF, Chatenoud L. CD3 antibodies as unique tools to restore self-tolerance in established autoimmunity their mode of action and clinical application in type 1 diabetes. Adv Immunol. 2008;100:13-37. doi: 10.1016/S0065-2776(08)00802-X. No abstract available.

Results Reference

background

Links:

URL

http://www.defendagainstdiabetes.com/

Description

Website containing information on DEFEND study

Available IPD and Supporting Information:

Available IPD/Information Type

Clinical Study Report

Available IPD/Information URL

https://www.clinicalstudydatarequest.com

Available IPD/Information Identifier

115495

Available IPD/Information Comments

For additional information about this study please refer to the GSK Clinical Study Register

Available IPD/Information Type

Individual Participant Data Set

Available IPD/Information URL

https://www.clinicalstudydatarequest.com

Available IPD/Information Identifier

115495

Available IPD/Information Comments

For additional information about this study please refer to the GSK Clinical Study Register

Available IPD/Information Type

Annotated Case Report Form

Available IPD/Information URL

https://www.clinicalstudydatarequest.com

Available IPD/Information Identifier

115495

Available IPD/Information Comments

For additional information about this study please refer to the GSK Clinical Study Register

Available IPD/Information Type

Statistical Analysis Plan

Available IPD/Information URL

https://www.clinicalstudydatarequest.com

Available IPD/Information Identifier

115495

Available IPD/Information Comments

For additional information about this study please refer to the GSK Clinical Study Register

Available IPD/Information Type

Study Protocol

Available IPD/Information URL

https://www.clinicalstudydatarequest.com

Available IPD/Information Identifier

115495

Available IPD/Information Comments

For additional information about this study please refer to the GSK Clinical Study Register

Available IPD/Information Type

Dataset Specification

Available IPD/Information URL

https://www.clinicalstudydatarequest.com

Available IPD/Information Identifier

115495

Available IPD/Information Comments

For additional information about this study please refer to the GSK Clinical Study Register

Available IPD/Information Type

Informed Consent Form

Available IPD/Information URL

https://www.clinicalstudydatarequest.com

Available IPD/Information Identifier

115495

Available IPD/Information Comments

For additional information about this study please refer to the GSK Clinical Study Register

Learn more about this trial

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

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

Diabetes Mellitus, Type 1

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial