New-onset Type 1 Diabetes Mellitus
Conditions
Keywords
New-onset Type 1 Diabetes Mellitus, New-onset T1DM, New-onset Type 1 Diabetes, New-onset T1D, Newly Diagnosed Type 1 Diabetes Mellitus, Autoimmune diabetes, Thymoglobulin, ATG, Rabbit antithymocyte globulin
Brief summary
Antithymocyte globulin (e.g., Thymoglobulin®) is an antibody preparation that is commonly used to treat and prevent organ transplant rejection. The START trial aims to determine whether antithymocyte globulin (ATG) treatment can halt the progression of newly diagnosed type 1 diabetes when given within 12 weeks of disease diagnosis.
Detailed description
Type 1 diabetes mellitus (T1DM) is an autoimmune disease in which the immune system mistakenly attacks the insulin-producing beta cells in the pancreas. Without these cells, the body cannot maintain proper blood glucose levels in response to daily activities, such as eating or exercise. Generally, at the time someone is diagnosed with T1DM, not all of a person's beta cells have been destroyed - between 15-40% remain healthy and are still able to produce insulin. Importantly, even small amounts of naturally produced insulin can improve blood sugar control, make daily management of diabetes less complicated, and reduce the risk of long term complications. Preserving the remaining precious beta cells is therefore the goal of the START trial. The medication being tested in the START trial is antithymocyte globulin (e.g., Thymoglobulin®), a mixture of specialized proteins called antibodies. ATG attaches itself to white blood cells known as T cells, some of which are responsible for the immune system's attack on beta cells that occurs in T1DM. ATG can change how T cells work, and can eliminate a large proportion of the T cells from the bloodstream temporarily. Treatment of new onset T1DM with ATG is therefore expected to alter the behavior of the T cells to halt their attack, and also reduce T cell numbers, so that new T cells that grow in their place will learn to accept the beta cells, rather than attacking them. Following an initial screening appointment, eligible participants will be randomly assigned to one of two groups: the Experimental Group will receive the study treatment while the Control Group that will receive placebo. Each participant has a 2 in 3 chance of being assigned to the treatment group, and a 1 in 3 chance of being assigned to the placebo. The START trial is a blinded study, so neither participants nor study physicians will know to which group an individual has been assigned. All participants will receive intensive diabetes management. Participants in both groups will be admitted to the hospital for 5-8 days to receive infusions of either the study drug or placebo. The duration of the study is 2 years. Participants will have 8 follow-up appointments in the first year and 4 visits in the second year. Most of these visits will last 1- 2 hours. A review of interval health, a physical exam, an assessment of diabetes control including recent 5 day insulin use and blood sugar (e.g., glucose) testing, and blood collection for laboratory testing will occur at each visit. Four of the visits will last about 5 hours, during which participants will undergo mixed-meal tolerance testing (MMTT). This involves drinking a special drink, similar to a milkshake, and having blood specimens taken over a 4-hour period. Subjects will be reimbursed for travel and parking expenses, and will receive compensation for their participation in the longer mixed meal tolerance test visits.
Interventions
DRUGAntithymocyte globulin
Daily 4-day escalating dose
DRUGPlacebo
Daily 4-day saline solution
Sponsors
Immune Tolerance Network (ITN)
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
12 Years to 35 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of type 1 diabetes (according to American Diabetes Association \[ADA\] criteria) within100 days of enrollment * Positive for one or more autoantibodies (anti-glutamic acid decarboxylase \[GAD\], anti-insulin, or IA-2 autoantibodies) * Peak stimulated C-peptide level \>0.4 pmol/mL or \>1.2ng/mL following an MMTT * Serologic evidence of prior Epstein-Barr virus (EBV) infection (EBV seropositive) * Willing to use acceptable forms of contraception
Exclusion criteria
* Any sign of active infection (e.g., hepatitis, tuberculosis, EBV, cytomegalovirus (CMV), or toxoplasmosis) at screening * Positive for human immunodeficiency virus (HIV), tuberculosis, or hepatitis B surface antigen (HBsAg) at screening * Prior history of any significant cardiac disease, such as congestive heart failure, arrhythmia, or structural defects, or suspicion thereof * Use of glucocorticoids in the 28 days prior to study entry; or topical use of glucocorticoids * Use of diabetes medications (other than insulin) that may affect glucose homeostasis, such as metformin, sulfonylureas, thiazolidinediones, or amylin * Evidence of liver dysfunction * Evidence of kidney disease * Pregnancy or plan to become pregnant * Leukopenia (\<3,000 leukocytes/µL), neutropenia (\<1,500neutrophils/µL), lymphopenia (\<800 lymphocytes/µL), or thrombocytopenia (\<125,000 platelets/µL). * Prior treatment with rabbit ATG or known hypersensitivity or exposure to rabbit sera-derived products * Vaccination with a live virus within the last 6 weeks before enrollment * Prior or current therapy that is known to cause a significant, ongoing change in the course of T1DM or immunologic status * Any condition that may compromise study participation or may confound the interpretation of the study results
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 2-Hour C-peptide Area Under the Curve (AUC) Result in Response to Standardized Mixed Meal Tolerance Test (MMTT) | Baseline (Pre-treatment initiation), Month 12 | C-peptide is a substance released by the pancreas into the bloodstream in equal amounts to insulin and reflects how much insulin pancreatic beta cells are making. The standardized MMTT evaluates whether beta cells are producing endogenous insulin. The MMTT was performed in the morning and blood samples for C-peptide collected at baseline (pre-meal) and 15, 30, 60, 90, 120, 150, 180, 210,and 240 minutes post-meal. Results of the stimulated 2-hour (e.g., 120 minutes) post-meal C-peptide AUC are provided. Larger numbers are preferable (better) in these AUC results: more insulin being produced reflects less severe disease. C-peptide levels in the serum (e.g., AUC following a standardized MMTT) compared to control group at 1 year post treatment initiation for the evaluation of investigational products intended to preserve endogenous beta-cell function in T1DM trials is recognized by the Center for Drug Evaluation and Research (CDER) at the FDA as a valid efficacy primary endpoint. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Insulin Use in Units Per Kilogram Body Weight Per Day | Baseline (Pre-treatment), Months 12 and 24 | The need to use exogenous insulin is an indication that the body is not producing enough endogenous insulin. Higher amounts of insulin use indicate higher disease activity. |
| Number of Participants Who Are Exogenous-Insulin-Free | Baseline (Pre-treatment), Months 12 , 18, and 24 | The need to use exogenous insulin is an indication that the body is not producing enough endogenous insulin. Higher amounts of insulin use indicate higher disease activity. |
| 4-Hour C-peptide Area Under the Curve (AUC) Result in Response to Standardized Mixed Meal Tolerance Test (MMTT) | Baseline (Pre-treatment initiation), Month 12 | C-peptide is a substance released by the pancreas into the bloodstream in equal amounts to insulin and reflects how much insulin pancreatic beta cells are making. The standardized MMTT evaluates whether beta cells are producing endogenous insulin. The MMTT was performed in the morning and blood samples for C-peptide collected at baseline (pre-meal) and 15, 30, 60, 90, 120, 150, 180, 210,and 240 minutes post-meal. Results of the stimulated 4-hour (e.g., 240 minutes) post-meal C-peptide AUC are provided. Larger numbers are preferable (better) in these AUC results: more insulin being produced reflects less severe disease. C-peptide levels in the serum (e.g., AUC following a standardized MMTT) compared to control group at 1 year post treatment initiation for the evaluation of investigational products intended to preserve endogenous beta-cell function in T1DM trials is recognized by the Center for Drug Evaluation and Research (CDER) at the FDA as a valid efficacy endpoint. |
| 2-Hour and 4-Hour C-peptide Area Under the Curve (AUC) Results in Response to Standardized Mixed Meal Tolerance Test (MMTT) | Baseline (Pre-treatment), Month 24 | C-peptide is a substance released by the pancreas into the bloodstream in equal amounts to insulin and reflects how much insulin pancreatic beta cells are making. The standardized MMTT evaluates whether beta cells are producing endogenous insulin. The MMTT was performed in the morning and blood samples for C-peptide collected at baseline (pre-meal) and 15, 30, 60, 90, 120, 150, 180, 210,and 240 minutes post-meal. Results of the stimulated 2-hour (e.g., 120 minutes) and 4-hour (e.g., 240 minutes) post-meal C-peptide AUC are provided. Larger numbers are preferable (better) in these AUC results: more insulin being produced reflects less severe disease. C-peptide levels in the serum (e.g., AUC following a standardized MMTT) compared to control group at 1 year post treatment initiation for the evaluation of investigational products intended to preserve endogenous beta-cell function in T1DM trials is recognized by the CDER at the FDA as a valid efficacy endpoint. |
| Hemoglobin A1c | Baseline (Pre-treatment), Months 12 and 24 | Glycosylated hemoglobin (HbA1c) is a measure of the average plasma concentration of blood sugar (glucose) over the previous three months and measures the level of optimal management of underlying disease. An HbA1c of \<\\=5.6% is considered normal. HbA1c of 6.5% or higher is typical for individuals with Type 1 Diabetes mellitus (T1DM). |
| Number of Participants With Major Hypoglycemic Event(s) Post Treatment Randomization/Initiation | Baseline (Pre-treatment), Months 12 , and 24 | Major hypoglycemic events are defined as a glucose concentration \<55 mg/dL (grades 2-5, NCI-CTCAE version 3.0), or clinically: involving seizure(s) or involving loss of consciousness (coma), or requiring assistance from another individual in order to recover. |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited during an approximate 40-month accrual period. Initially 66 subjects were planned, however enrollment closed early at 58 subjects on June 30, 2011 secondary to slow accrual (planned 30-month accrual period).
Pre-assignment details
Subjects ages 12 to 35 years who were first diagnosed with type 1 diabetes mellitus (T1DM) within 100 days of enrollment.
Participants by arm
| Arm | Count |
|---|---|
| Antithymocyte Globulin This group received a total of 6.5 mg/kg of antithymocyte globulin (Thymoglobulin®) administered intravenously and divided into four doses as follows: Day 1, 0.5 mg/kg; Day 2, 2 mg/kg; Day 3, 2 mg/kg; and Day 4, 2 mg/kg. | 38 |
| Placebo This group received a saline solution administered intravenously to match the antithymocyte globulin (Thymoglobulin®) doses given to the active treatment group, on Day 1, 0.5 mg/kg; Day 2, 2 mg/kg; Day 3, 2 mg/kg; and Day 4, 2 mg/kg. | 20 |
| Total | 58 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | IRB Recommendation | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 4 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Antithymocyte Globulin | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 19 Participants | 10 Participants | 29 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 19 Participants | 10 Participants | 29 Participants |
| Age, Continuous | 19.4 years STANDARD_DEVIATION 6.6 | 20.5 years STANDARD_DEVIATION 7.1 | 19.8 years STANDARD_DEVIATION 6.7 |
| Age, Customized 12 -15 Years | 13 participants | 6 participants | 19 participants |
| Age, Customized 16 - 21 Years | 13 participants | 6 participants | 19 participants |
| Age, Customized 22 - 35 Years | 12 participants | 8 participants | 20 participants |
| Region of Enrollment United States | 38 participants | 20 participants | 58 participants |
| Sex: Female, Male Female | 14 Participants | 9 Participants | 23 Participants |
| Sex: Female, Male Male | 24 Participants | 11 Participants | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 38 / 38 | 20 / 20 |
| serious Total, serious adverse events | 9 / 38 | 4 / 20 |
Outcome results
Primary
2-Hour C-peptide Area Under the Curve (AUC) Result in Response to Standardized Mixed Meal Tolerance Test (MMTT)
C-peptide is a substance released by the pancreas into the bloodstream in equal amounts to insulin and reflects how much insulin pancreatic beta cells are making. The standardized MMTT evaluates whether beta cells are producing endogenous insulin. The MMTT was performed in the morning and blood samples for C-peptide collected at baseline (pre-meal) and 15, 30, 60, 90, 120, 150, 180, 210,and 240 minutes post-meal. Results of the stimulated 2-hour (e.g., 120 minutes) post-meal C-peptide AUC are provided. Larger numbers are preferable (better) in these AUC results: more insulin being produced reflects less severe disease. C-peptide levels in the serum (e.g., AUC following a standardized MMTT) compared to control group at 1 year post treatment initiation for the evaluation of investigational products intended to preserve endogenous beta-cell function in T1DM trials is recognized by the Center for Drug Evaluation and Research (CDER) at the FDA as a valid efficacy primary endpoint.
Time frame: Baseline (Pre-treatment initiation), Month 12
Population: Intent-to-treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Antithymocyte Globulin | 2-Hour C-peptide Area Under the Curve (AUC) Result in Response to Standardized Mixed Meal Tolerance Test (MMTT) | Baseline (Pre-treatment initiation) | 0.86 pmol/mL | Standard Deviation 0.37 |
| Antithymocyte Globulin | 2-Hour C-peptide Area Under the Curve (AUC) Result in Response to Standardized Mixed Meal Tolerance Test (MMTT) | Month 12 | 0.66 pmol/mL | Standard Deviation 0.37 |
| Antithymocyte Globulin | 2-Hour C-peptide Area Under the Curve (AUC) Result in Response to Standardized Mixed Meal Tolerance Test (MMTT) | Change from Baseline (Pre-treatment initiation) | -0.20 pmol/mL | Standard Deviation 0.29 |
| Placebo | 2-Hour C-peptide Area Under the Curve (AUC) Result in Response to Standardized Mixed Meal Tolerance Test (MMTT) | Baseline (Pre-treatment initiation) | 0.93 pmol/mL | Standard Deviation 0.5 |
| Placebo | 2-Hour C-peptide Area Under the Curve (AUC) Result in Response to Standardized Mixed Meal Tolerance Test (MMTT) | Month 12 | 0.69 pmol/mL | Standard Deviation 0.52 |
| Placebo | 2-Hour C-peptide Area Under the Curve (AUC) Result in Response to Standardized Mixed Meal Tolerance Test (MMTT) | Change from Baseline (Pre-treatment initiation) | -0.24 pmol/mL | Standard Deviation 0.26 |
Comparison: Primary imputation method used for missing Month 12 AUC. Measuring range for C-peptide is 0.05-30 ng/mLp-value: 0.6ANCOVA
Secondary
2-Hour and 4-Hour C-peptide Area Under the Curve (AUC) Results in Response to Standardized Mixed Meal Tolerance Test (MMTT)
C-peptide is a substance released by the pancreas into the bloodstream in equal amounts to insulin and reflects how much insulin pancreatic beta cells are making. The standardized MMTT evaluates whether beta cells are producing endogenous insulin. The MMTT was performed in the morning and blood samples for C-peptide collected at baseline (pre-meal) and 15, 30, 60, 90, 120, 150, 180, 210,and 240 minutes post-meal. Results of the stimulated 2-hour (e.g., 120 minutes) and 4-hour (e.g., 240 minutes) post-meal C-peptide AUC are provided. Larger numbers are preferable (better) in these AUC results: more insulin being produced reflects less severe disease. C-peptide levels in the serum (e.g., AUC following a standardized MMTT) compared to control group at 1 year post treatment initiation for the evaluation of investigational products intended to preserve endogenous beta-cell function in T1DM trials is recognized by the CDER at the FDA as a valid efficacy endpoint.
Time frame: Baseline (Pre-treatment), Month 24
Population: Intent-to-treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Antithymocyte Globulin | 2-Hour and 4-Hour C-peptide Area Under the Curve (AUC) Results in Response to Standardized Mixed Meal Tolerance Test (MMTT) | 2-hour AUC Month 24 | 0.58 pmol/mL | Standard Deviation 0.43 |
| Antithymocyte Globulin | 2-Hour and 4-Hour C-peptide Area Under the Curve (AUC) Results in Response to Standardized Mixed Meal Tolerance Test (MMTT) | 4-hour AUC Month 24 | 0.56 pmol/mL | Standard Deviation 0.36 |
| Antithymocyte Globulin | 2-Hour and 4-Hour C-peptide Area Under the Curve (AUC) Results in Response to Standardized Mixed Meal Tolerance Test (MMTT) | Change from 2-hr MMTT Baseline | -0.27 pmol/mL | Standard Deviation 0.31 |
| Antithymocyte Globulin | 2-Hour and 4-Hour C-peptide Area Under the Curve (AUC) Results in Response to Standardized Mixed Meal Tolerance Test (MMTT) | Change from 4-hr MMTT Baseline | -0.26 pmol/mL | Standard Deviation 0.28 |
| Antithymocyte Globulin | 2-Hour and 4-Hour C-peptide Area Under the Curve (AUC) Results in Response to Standardized Mixed Meal Tolerance Test (MMTT) | Baseline (Pre-treatment initiation) | 0.86 pmol/mL | Standard Deviation 0.37 |
| Placebo | 2-Hour and 4-Hour C-peptide Area Under the Curve (AUC) Results in Response to Standardized Mixed Meal Tolerance Test (MMTT) | Change from 4-hr MMTT Baseline | -0.31 pmol/mL | Standard Deviation 0.38 |
| Placebo | 2-Hour and 4-Hour C-peptide Area Under the Curve (AUC) Results in Response to Standardized Mixed Meal Tolerance Test (MMTT) | Baseline (Pre-treatment initiation) | 0.93 pmol/mL | Standard Deviation 0.5 |
| Placebo | 2-Hour and 4-Hour C-peptide Area Under the Curve (AUC) Results in Response to Standardized Mixed Meal Tolerance Test (MMTT) | 2-hour AUC Month 24 | 0.61 pmol/mL | Standard Deviation 0.67 |
| Placebo | 2-Hour and 4-Hour C-peptide Area Under the Curve (AUC) Results in Response to Standardized Mixed Meal Tolerance Test (MMTT) | Change from 2-hr MMTT Baseline | -0.32 pmol/mL | Standard Deviation 0.32 |
| Placebo | 2-Hour and 4-Hour C-peptide Area Under the Curve (AUC) Results in Response to Standardized Mixed Meal Tolerance Test (MMTT) | 4-hour AUC Month 24 | 0.59 pmol/mL | Standard Deviation 0.63 |
Comparison: 2-Hour AUC change from baseline (pre-initiation treatment) to Month 24. Primary imputation method used for missing Month 24 AUC. Measuring range for C-peptide is 0.05-30 ng/mL.p-value: 0.38ANCOVA
Comparison: 4-Hour AUC change from baseline (pre-initiation treatment) to Month 24. Missing Month 24 AUC values were not imputed. Measuring range for C-peptide is 0.05-30 ng/mL.p-value: 0.33ANCOVA
Secondary
4-Hour C-peptide Area Under the Curve (AUC) Result in Response to Standardized Mixed Meal Tolerance Test (MMTT)
C-peptide is a substance released by the pancreas into the bloodstream in equal amounts to insulin and reflects how much insulin pancreatic beta cells are making. The standardized MMTT evaluates whether beta cells are producing endogenous insulin. The MMTT was performed in the morning and blood samples for C-peptide collected at baseline (pre-meal) and 15, 30, 60, 90, 120, 150, 180, 210,and 240 minutes post-meal. Results of the stimulated 4-hour (e.g., 240 minutes) post-meal C-peptide AUC are provided. Larger numbers are preferable (better) in these AUC results: more insulin being produced reflects less severe disease. C-peptide levels in the serum (e.g., AUC following a standardized MMTT) compared to control group at 1 year post treatment initiation for the evaluation of investigational products intended to preserve endogenous beta-cell function in T1DM trials is recognized by the Center for Drug Evaluation and Research (CDER) at the FDA as a valid efficacy endpoint.
Time frame: Baseline (Pre-treatment initiation), Month 12
Population: Intent-to-treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Antithymocyte Globulin | 4-Hour C-peptide Area Under the Curve (AUC) Result in Response to Standardized Mixed Meal Tolerance Test (MMTT) | Baseline (Pre-treatment initiation) | 0.86 pmol/mL | Standard Deviation 0.3 |
| Antithymocyte Globulin | 4-Hour C-peptide Area Under the Curve (AUC) Result in Response to Standardized Mixed Meal Tolerance Test (MMTT) | Month 12 | 0.67 pmol/mL | Standard Deviation 0.38 |
| Antithymocyte Globulin | 4-Hour C-peptide Area Under the Curve (AUC) Result in Response to Standardized Mixed Meal Tolerance Test (MMTT) | Change from Baseline (Pre-treatment initiation) | -0.19 pmol/mL | Standard Deviation 0.3 |
| Placebo | 4-Hour C-peptide Area Under the Curve (AUC) Result in Response to Standardized Mixed Meal Tolerance Test (MMTT) | Baseline (Pre-treatment initiation) | 0.90 pmol/mL | Standard Deviation 0.37 |
| Placebo | 4-Hour C-peptide Area Under the Curve (AUC) Result in Response to Standardized Mixed Meal Tolerance Test (MMTT) | Month 12 | 0.63 pmol/mL | Standard Deviation 0.39 |
| Placebo | 4-Hour C-peptide Area Under the Curve (AUC) Result in Response to Standardized Mixed Meal Tolerance Test (MMTT) | Change from Baseline (Pre-treatment initiation) | -0.27 pmol/mL | Standard Deviation 0.25 |
Comparison: Missing Month 12 AUC values were not imputed. Measuring range for C-peptide is 0.05-30 ng/mLp-value: 0.4ANCOVA
Secondary
Hemoglobin A1c
Glycosylated hemoglobin (HbA1c) is a measure of the average plasma concentration of blood sugar (glucose) over the previous three months and measures the level of optimal management of underlying disease. An HbA1c of \<\\=5.6% is considered normal. HbA1c of 6.5% or higher is typical for individuals with Type 1 Diabetes mellitus (T1DM).
Time frame: Baseline (Pre-treatment), Months 12 and 24
Population: Intent-to-treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Antithymocyte Globulin | Hemoglobin A1c | Month 12 | 6.9 Percentage (%) | Standard Deviation 1.6 |
| Antithymocyte Globulin | Hemoglobin A1c | Month 24 | 7.5 Percentage (%) | Standard Deviation 1.5 |
| Antithymocyte Globulin | Hemoglobin A1c | Change from Baseline to Month 12 | 0.1 Percentage (%) | Standard Deviation 1.8 |
| Antithymocyte Globulin | Hemoglobin A1c | Change from Baseline to Month 24 | 0.6 Percentage (%) | Standard Deviation 1.8 |
| Antithymocyte Globulin | Hemoglobin A1c | Baseline (Pre-treatment initiation) | 6.7 Percentage (%) | Standard Deviation 1.3 |
| Placebo | Hemoglobin A1c | Change from Baseline to Month 24 | 1.4 Percentage (%) | Standard Deviation 1.9 |
| Placebo | Hemoglobin A1c | Baseline (Pre-treatment initiation) | 6.8 Percentage (%) | Standard Deviation 1.2 |
| Placebo | Hemoglobin A1c | Month 12 | 7.7 Percentage (%) | Standard Deviation 1.8 |
| Placebo | Hemoglobin A1c | Change from Baseline to Month 12 | 1.0 Percentage (%) | Standard Deviation 1.5 |
| Placebo | Hemoglobin A1c | Month 24 | 8.2 Percentage (%) | Standard Deviation 2.4 |
Comparison: Comparison of groups for change from Baseline to Month 12p-value: 0.07ANCOVA
Comparison: Comparison of groups for change from Baseline to Month 24p-value: 0.16ANCOVA
Secondary
Insulin Use in Units Per Kilogram Body Weight Per Day
The need to use exogenous insulin is an indication that the body is not producing enough endogenous insulin. Higher amounts of insulin use indicate higher disease activity.
Time frame: Baseline (Pre-treatment), Months 12 and 24
Population: Intent-to-treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Antithymocyte Globulin | Insulin Use in Units Per Kilogram Body Weight Per Day | Baseline (Pre-treatment initiation) | 0.34 units/day/kg | Standard Deviation 0.22 |
| Antithymocyte Globulin | Insulin Use in Units Per Kilogram Body Weight Per Day | Month 24 | 0.54 units/day/kg | Standard Deviation 0.31 |
| Antithymocyte Globulin | Insulin Use in Units Per Kilogram Body Weight Per Day | Change from Baseline to Month 12 | 0.07 units/day/kg | Standard Deviation 0.2 |
| Antithymocyte Globulin | Insulin Use in Units Per Kilogram Body Weight Per Day | Change from Baseline to Month 24 | 0.19 units/day/kg | Standard Deviation 0.23 |
| Antithymocyte Globulin | Insulin Use in Units Per Kilogram Body Weight Per Day | Month 12 | 0.40 units/day/kg | Standard Deviation 0.24 |
| Placebo | Insulin Use in Units Per Kilogram Body Weight Per Day | Change from Baseline to Month 24 | 0.06 units/day/kg | Standard Deviation 0.25 |
| Placebo | Insulin Use in Units Per Kilogram Body Weight Per Day | Baseline (Pre-treatment initiation) | 0.42 units/day/kg | Standard Deviation 0.24 |
| Placebo | Insulin Use in Units Per Kilogram Body Weight Per Day | Month 12 | 0.49 units/day/kg | Standard Deviation 0.26 |
| Placebo | Insulin Use in Units Per Kilogram Body Weight Per Day | Change from Baseline to Month 12 | 0.08 units/day/kg | Standard Deviation 0.2 |
| Placebo | Insulin Use in Units Per Kilogram Body Weight Per Day | Month 24 | 0.47 units/day/kg | Standard Deviation 0.21 |
Comparison: Comparison of groups for change from baseline (pre-treatment initiation) to Month 12p-value: 0.59ANCOVA
Comparison: Comparison of groups for change from baseline (pre-treatment initiation) to Month 24p-value: 0.14ANCOVA
Secondary
Number of Participants Who Are Exogenous-Insulin-Free
The need to use exogenous insulin is an indication that the body is not producing enough endogenous insulin. Higher amounts of insulin use indicate higher disease activity.
Time frame: Baseline (Pre-treatment), Months 12 , 18, and 24
Population: Intent-to-treat
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Antithymocyte Globulin | Number of Participants Who Are Exogenous-Insulin-Free | Month 24 | 1 participants |
| Antithymocyte Globulin | Number of Participants Who Are Exogenous-Insulin-Free | Baseline (Pre-treatment initiation) | 1 participants |
| Antithymocyte Globulin | Number of Participants Who Are Exogenous-Insulin-Free | Month 12 | 1 participants |
| Antithymocyte Globulin | Number of Participants Who Are Exogenous-Insulin-Free | Month 18 | 1 participants |
| Placebo | Number of Participants Who Are Exogenous-Insulin-Free | Month 24 | 0 participants |
| Placebo | Number of Participants Who Are Exogenous-Insulin-Free | Month 18 | 0 participants |
| Placebo | Number of Participants Who Are Exogenous-Insulin-Free | Month 12 | 0 participants |
| Placebo | Number of Participants Who Are Exogenous-Insulin-Free | Baseline (Pre-treatment initiation) | 0 participants |
Secondary
Number of Participants With Major Hypoglycemic Event(s) Post Treatment Randomization/Initiation
Major hypoglycemic events are defined as a glucose concentration \<55 mg/dL (grades 2-5, NCI-CTCAE version 3.0), or clinically: involving seizure(s) or involving loss of consciousness (coma), or requiring assistance from another individual in order to recover.
Time frame: Baseline (Pre-treatment), Months 12 , and 24
Population: Intent-to-treat
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Antithymocyte Globulin | Number of Participants With Major Hypoglycemic Event(s) Post Treatment Randomization/Initiation | Participants with Hypoglycemic Events Up to Mo. 12 | 23 participants |
| Antithymocyte Globulin | Number of Participants With Major Hypoglycemic Event(s) Post Treatment Randomization/Initiation | Participants with Hypoglycemic Events Up to Mo. 24 | 30 participants |
| Placebo | Number of Participants With Major Hypoglycemic Event(s) Post Treatment Randomization/Initiation | Participants with Hypoglycemic Events Up to Mo. 12 | 12 participants |
| Placebo | Number of Participants With Major Hypoglycemic Event(s) Post Treatment Randomization/Initiation | Participants with Hypoglycemic Events Up to Mo. 24 | 15 participants |
Comparison: Comparison of groups up to Month 12p-value: >0.099Fisher Exact
Comparison: Comparison of groups up to Month 24p-value: 0.75Fisher Exact