| ID | Type | Description | Link |
|---|---|---|---|
| TRX4006 | Other Identifier | Tolerx |
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| Name | Class |
|---|---|
| Juvenile Diabetes Research Foundation | OTHER |
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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
The following visits are required:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| otelixizumab | Experimental | otelixizumab |
|
| placebo | Placebo Comparator | Placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| otelixizumab infusion plus physician determined standard of care | Biological | infusion |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline (0-120 minutes on Day 1) and Month 12 (0-120 minutes) |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Birmingham | Alabama | 35294 | United States | ||
| GSK Investigational Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 15972866 | Background | 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. | |
| 19111162 |
Not provided
| ID | Type | URL | Comment |
|---|---|---|---|
| 115495 | Clinical Study Report | View IPD |
Participants were screened for a period of 35 days and a total of 272 participants were randomized in the study.
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.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Adolescent (Placebo) | Eligible adolescent participants received matching placebo to Otelixizumab administered as intravenous (IV) infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per Day over 8 consecutive days. Participants were followed-up for 24 months after the last dose. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| placebo infusion plus physician determined standard of care | Biological | infusion |
|
| 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. | Week 12 and Months 6 and 12. |
| 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. | 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. | Upto Month 12 |
| 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. | Upto Month 12 |
| 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. | Week 12 and Months 6 and 12. |
| 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. | Week 12 and Months 6 and 12. |
| 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. | Week 12 and Months 6 and 12 |
| 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. | Week 12 and Months 6 and 12 |
| 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. | 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 | 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. | Week 12 and Months 6 and 12 |
| 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. | Baseline (Day 1) and Week 12, 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. | Month 6 and 12 |
| 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. | Month 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 | 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. | 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 | 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. | Baseline (pre-dose on Day 1) and up to 12 Months |
| 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. | Baseline (pre-dose on 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. | Baseline (Pre-dose Day 1), Day 4, 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. | Baseline (Pre-dose Day 1), Day 4, Day 8 |
| Little Rock |
| Arkansas |
| 72205 |
| United States |
| GSK Investigational Site | Costa Mesa | California | 92626 | United States |
| GSK Investigational Site | Los Angeles | California | 90033 | United States |
| GSK Investigational Site | Orange | California | 92868 | United States |
| GSK Investigational Site | Riverside | California | 92506 | United States |
| GSK Investigational Site | Santa Ana | California | 92705 | United States |
| GSK Investigational Site | Torrance | California | 90502 | United States |
| GSK Investigational Site | Walnut Creek | California | 94598 | United States |
| GSK Investigational Site | Aurora | Colorado | 80045 | United States |
| GSK Investigational Site | Washington D.C. | District of Columbia | 20037 | United States |
| GSK Investigational Site | Boca Raton | Florida | 33486 | United States |
| GSK Investigational Site | Jupiter | Florida | 33458 | United States |
| GSK Investigational Site | Miami | Florida | 33136 | United States |
| GSK Investigational Site | Miami | Florida | 33169 | United States |
| GSK Investigational Site | Orlando | Florida | 32803 | United States |
| GSK Investigational Site | Orlando | Florida | 32835 | United States |
| GSK Investigational Site | Pembroke Pines | Florida | 33024 | United States |
| GSK Investigational Site | Trinity | Florida | 34655 | United States |
| GSK Investigational Site | Winter Park | Florida | 32789 | United States |
| GSK Investigational Site | Atlanta | Georgia | 30309 | United States |
| GSK Investigational Site | Atlanta | Georgia | 30342 | United States |
| GSK Investigational Site | Honolulu | Hawaii | 96813 | United States |
| GSK Investigational Site | Boise | Idaho | 83702 | United States |
| GSK Investigational Site | Idaho Falls | Idaho | 83404-7542 | United States |
| GSK Investigational Site | Chicago | Illinois | 60612 | United States |
| GSK Investigational Site | Chicago | Illinois | 60637 | United States |
| GSK Investigational Site | Indianapolis | Indiana | 46260 | United States |
| GSK Investigational Site | Atlanta | Kansas | 21287 | United States |
| GSK Investigational Site | Topeka | Kansas | 66606 | United States |
| GSK Investigational Site | Baltimore | Maryland | 21201 | United States |
| GSK Investigational Site | Worcester | Massachusetts | 01655-0002 | United States |
| GSK Investigational Site | Detroit | Michigan | 48201 | United States |
| GSK Investigational Site | Kalamazoo | Michigan | 49048 | United States |
| GSK Investigational Site | Gulfport | Mississippi | 39501 | United States |
| GSK Investigational Site | Columbia | Missouri | 65212 | United States |
| GSK Investigational Site | Kansas City | Missouri | 64106 | United States |
| GSK Investigational Site | St Louis | Missouri | 63110 | United States |
| GSK Investigational Site | Omaha | Nebraska | 68131 | United States |
| GSK Investigational Site | Neptune City | New Jersey | 07753 | United States |
| GSK Investigational Site | Buffalo | New York | 14209 | United States |
| GSK Investigational Site | Mineola | New York | 11501 | United States |
| GSK Investigational Site | New York | New York | 10032 | United States |
| GSK Investigational Site | Rochester | New York | 14642 | United States |
| GSK Investigational Site | Durham | North Carolina | 27713 | United States |
| GSK Investigational Site | Columbus | Ohio | 43205 | United States |
| GSK Investigational Site | Columbus | Ohio | 43210 | United States |
| GSK Investigational Site | Dayton | Ohio | 45415-2560 | United States |
| GSK Investigational Site | Mentor | Ohio | 44060 | United States |
| GSK Investigational Site | Tulsa | Oklahoma | 74136-8303 | United States |
| GSK Investigational Site | Eugene | Oregon | 97401 | United States |
| GSK Investigational Site | Portland | Oregon | 97210 | United States |
| GSK Investigational Site | Langhorne | Pennsylvania | 19047 | United States |
| GSK Investigational Site | Philadelphia | Pennsylvania | 19140 | United States |
| GSK Investigational Site | Charleston | South Carolina | 29425-6240 | United States |
| GSK Investigational Site | Rapid City | South Dakota | 57701 | United States |
| GSK Investigational Site | Chattanooga | Tennessee | 37403 | United States |
| GSK Investigational Site | Memphis | Tennessee | 38119 | United States |
| GSK Investigational Site | Nashville | Tennessee | 37212 | United States |
| GSK Investigational Site | Dallas | Texas | 75231 | United States |
| GSK Investigational Site | Dallas | Texas | 75390 | United States |
| GSK Investigational Site | Houston | Texas | 77030 | United States |
| GSK Investigational Site | Hurst | Texas | 76054 | United States |
| GSK Investigational Site | San Antonio | Texas | 78229 | United States |
| GSK Investigational Site | Schertz | Texas | 782154 | United States |
| GSK Investigational Site | Ogden | Utah | 84403 | United States |
| GSK Investigational Site | Tacoma | Washington | 98405 | United States |
| GSK Investigational Site | Calgary | Alberta | T2H 2G4 | Canada |
| GSK Investigational Site | Oakville | Ontario | L6H 3P1 | Canada |
| GSK Investigational Site | Smiths Falls | Ontario | K7A 4W8 | Canada |
| GSK Investigational Site | Toronto | Ontario | M4G 3E8 | Canada |
| GSK Investigational Site | Montreal | Quebec | H2W 1T8 | Canada |
| GSK Investigational Site | Pointe-Claire | Quebec | H9R 3J1 | Canada |
| GSK Investigational Site | Arhus C | 8000 | Denmark |
| GSK Investigational Site | Tampere | 33520 | Finland |
| GSK Investigational Site | Turku | 20520 | Finland |
| GSK Investigational Site | Heidelberg | Baden-Wurttemberg | 69120 | Germany |
| GSK Investigational Site | Bad Nauheim | Hesse | 61231 | Germany |
| GSK Investigational Site | Bad Lauterberg im Harz | Lower Saxony | 37431 | Germany |
| GSK Investigational Site | Berlin | 12200 | Germany |
| GSK Investigational Site | Latina | Lazio | 04100 | Italy |
| GSK Investigational Site | Rome | Lazio | 00157 | Italy |
| GSK Investigational Site | Rome | Lazio | 00161 | Italy |
| GSK Investigational Site | Rome | Lazio | 00168 | Italy |
| GSK Investigational Site | Monserrato | Sardinia | 09042 | Italy |
| GSK Investigational Site | Palermo | Sicily | 90127 | Italy |
| GSK Investigational Site | Milan | 20132 | Italy |
| GSK Investigational Site | Roma | 00128 | Italy |
| GSK Investigational Site | Barcelona | 8035 | Spain |
| GSK Investigational Site | Girona | Spain |
| GSK Investigational Site | Madrid | 28040 | Spain |
| GSK Investigational Site | Sant Joan | ´03550 | Spain |
| GSK Investigational Site | Tarrasa, Barcelona | 08221 | Spain |
| GSK Investigational Site | Gothenburg | SE-413 45 | Sweden |
| GSK Investigational Site | Halmstad | SE-301 85 | Sweden |
| GSK Investigational Site | Härnösand | 871 82 | Sweden |
| GSK Investigational Site | Karlskrona | SE- 371 85 | Sweden |
| GSK Investigational Site | Karlstad | SE-651 85 | Sweden |
| GSK Investigational Site | Kristianstad | 291 85 | Sweden |
| GSK Investigational Site | Motala | SE-591 85 | Sweden |
| GSK Investigational Site | Stockholm | SE-171 76 | Sweden |
| GSK Investigational Site | Umeå | SE-901 85 | Sweden |
| GSK Investigational Site | Vaxjo | SE-351 85 | Sweden |
| GSK Investigational Site | Bath | Somerset | BA1 3NG | United Kingdom |
| GSK Investigational Site | Blackburn | BB2 3HH | United Kingdom |
| GSK Investigational Site | Bristol | BS2 8HW | United Kingdom |
| GSK Investigational Site | Hull | HU3 2RW | United Kingdom |
| GSK Investigational Site | London | SE1 9RT | United Kingdom |
| GSK Investigational Site | Newcastle upon Tyne | NE1 4LP | United Kingdom |
| Background |
| 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. |
For additional information about this study please refer to the GSK Clinical Study Register |
| 115495 | Individual Participant Data Set | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 115495 | Annotated Case Report Form | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 115495 | Statistical Analysis Plan | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 115495 | Study Protocol | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 115495 | Dataset Specification | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 115495 | Informed Consent Form | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| FG001 |
| Adolescent (Otelixizumab) |
Eligible adolescent participants received Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions as first dose (Day 1 of 0.1 milligram [mg], second dose (Day 2 of 0.2 mg), third dose (Day 3 of 0.3 mg), fourth, fifth, sixth, seventh and eight dose (on Days 4,5,6,7,8 of 0.5 mg per Day) 1 infusion per Day over 8 consecutive days . The total amount of Otelixizumab administered was 3.1 mg. Participants were followed-up for 24 months after the last dose. |
| FG002 | Adult (Placebo) | Eligible adult participants received matching placebo to Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions, 1 infusion per day over 8 consecutive Days. Participants were followed-up for 24 months after the last dose. |
| FG003 | Adult (Otelixizumab) | Eligible adult participants received Otelixizumab administered as IV infusions, with each infusion given over a 30-minute period. Participants received a series of 8 infusions as first dose (Day 1 of 0.1 mg), second dose (Day 2 of 0.2 mg), third dose (Day 3 of 0.3 mg), fourth, fifth, sixth, seventh and eight dose (on Days 4,5,6,7,8 of 0.5 mg per Day) 1 infusion per Day over 8 consecutive days . The total amount of Otelixizumab administered was 3.1 mg. Participants were followed-up for 24 months after the last dose. |
| COMPLETED |
|
| NOT COMPLETED |
|
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | 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. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Intent-to-treat (ITT) population, comprised of all participants who were randomized and received any part of at least 1 infusion of study drug. | Posted | Least Squares Mean | Standard Error | nanomoles per liter | Baseline (0-120 minutes on Day 1) and Month 12 (0-120 minutes) |
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| 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. | ITT population. Only those participants available at the specified time points were analyzed. | Posted | Count of Participants | Participants | Week 12 and Months 6 and 12 |
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| 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. | ITT population. | Posted | Least Squares Mean | Standard Error | IU/kg | Week 12 and Months 6 and 12. |
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| 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. | ITT population. | Posted | Least Squares Mean | Standard Error | Percentage | Week 12 and Months 6 and 12 |
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| 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. | ITT population. | Posted | Number | Hypoglycemic events | Upto Month 12 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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. | 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. | Posted | Count of Participants | Participants | Upto Month 12 |
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| 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. | ITT population. Only those participants available at the specified time points were analyzed. | Posted | Mean | Standard Error | Hypoglycemic excursions | Week 12 and Months 6 and 12. |
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| 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. | ITT population. Only those participants available at the specified time points were analyzed. | Posted | Mean | Standard Error | milligrams per deciliter | Week 12 and Months 6 and 12. |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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. | ITT population. Only those participants available at the specified time points were analyzed. | Posted | Count of Participants | Participants | Week 12 and Months 6 and 12 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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. | ITT population. Only those participants available at the specified time points were analyzed. | Posted | Mean | Standard Error | Hyperglycemic excursions | Week 12 and Months 6 and 12 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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. | ITT population. Only those participants available at the specified time points were analyzed. | Posted | Mean | Standard Error | milligrams per deciliter | Week 12 and Months 6 and 12. |
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| 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. | ITT population. Only those participants available at the specified time points were analyzed. | Posted | Count of Participants | Participants | Week 12 and Months 6 and 12 |
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| 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. | ITT population. | Posted | Least Squares Mean | Standard Error | Ratio | Baseline (Day 1) and Week 12, Months 6 and 12. |
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| 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. | ITT population. Only those participants available at the specified time points were analyzed. | Posted | Mean | Standard Deviation | Composite rank score | Month 6 and 12 |
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| 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. | ITT population. Only those participants available at the specified time points were analyzed. | Posted | Mean | Standard Deviation | Composite rank score | Month 6 and 12 |
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| 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. | ITT population. Only those participants available at the specified time points were analyzed. | Posted | Mean | Standard Error | picograms per milliliter | Day 1, Day 4, Day 8 |
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| 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. | ITT population. Only those participants available at the specified time points were analyzed. | Posted | Median | Full Range | Percent change | Baseline (pre-dose on Day 1) and up to 12 Months |
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| 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. | ITT population. Only those participants available at the specified time points were analyzed. | Posted | Mean | Standard Error | Percent change | Baseline (pre-dose on Day 1), Day 4 and Day 8 |
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| 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. | ITT population. Only those participants available at the specified time points were analyzed. | Posted | Mean | Standard Error | Percent change | Baseline (Pre-dose Day 1), Day 4, Day 8 |
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| 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. | ITT population. Only those participants available at the specified time points were analyzed. | Posted | Mean | Standard Error | Percent change | Baseline (Pre-dose Day 1), Day 4, Day 8 |
|
Upto Month 24
Safety was used for analysis which comprised of all participants who received any part of at least 1 infusion of study drug.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. | 0 | 91 | 6 | 91 | 81 | 91 |
| EG001 | 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. | 0 | 181 | 15 | 181 | 173 | 181 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anal abscess | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Appendicitis | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Gastroenteritis viral | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Septic embolus | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Tonsillitis | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Viral upper respiratory tract infection | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Cytokine release syndrome | Immune system disorders | MedDRA | Systematic Assessment |
| |
| Alcohol poisoning | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
| |
| Ligament rupture | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
| |
| Road traffic accident | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
| |
| Anal fistula | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Gastritis erosive | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
| |
| Hypoglycaemic seizure | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
| |
| Neurological symptom | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Alcohol abuse | Psychiatric disorders | MedDRA | Systematic Assessment |
| |
| Major depression | Psychiatric disorders | MedDRA | Systematic Assessment |
| |
| Cholelithiasis | Hepatobiliary disorders | MedDRA | Systematic Assessment |
| |
| Intervertebral disc protrusion | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
| |
| Abortion missed | Pregnancy, puerperium and perinatal conditions | MedDRA | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA | Systematic Assessment |
| |
| Chills | General disorders | MedDRA | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
| |
| Blood creatine phosphokinase increased | Investigations | MedDRA | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
| |
| Pharyngitis | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Rash macular | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
| |
| Malaise | General disorders | MedDRA | Systematic Assessment |
| |
| Rash papular | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
| |
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA | Systematic Assessment |
| |
| Sinus congestion | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
| |
| Viral infection | Infections and infestations | MedDRA | Systematic Assessment |
|
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| GSK Response Center | GlaxoSmithKline | 866-435-7343 |
| ID | Term |
|---|---|
| D003922 | Diabetes Mellitus, Type 1 |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D000911 | Antibodies, Monoclonal |
| C550701 | otelixizumab |
| D016853 | Muromonab-CD3 |
| ID | Term |
|---|---|
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D058846 | Antibodies, Monoclonal, Murine-Derived |
| D007074 | Immunoglobulin G |
| D007132 | Immunoglobulin Isotypes |
Not provided
Not provided
| Male |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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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.
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| Units |
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| Counts |
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| Participants |
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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. |
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| OG001 | 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. |
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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. |
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| OG001 |
| 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. |
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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. |
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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.
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| 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. |
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| 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. |
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| OG001 |
| 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. |
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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.
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| 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. |
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