Type 1 Diabetes Mellitus
Conditions
Keywords
immune therapy, autoimmunity, insulin secretion, diabetes mellitus
Brief summary
This is a randomized placebo controlled study to test whether a single 14 course of treatment with the anti-CD3 monoclonal antibody, hOKT3gamma1(Ala-Ala),Teplizumab will prevent the loss of insulin secretory capacity in individuals with Type 1 diabetes of 4 - 12 months duration since diagnosis.
Detailed description
The study design is a double blind placebo controlled trial that will enroll subjects between the ages of 8 - 30 who have had the diagnosis of Type 1 diabetes made 4 - 12 months prior to enrollment. A single 14 course of treatment with mAb hOKT3gamma1(Ala-Ala), Teplizumab will be given. The primary endpoint is the C-peptide response to a mixed meal at 12 months. A total of 60 subjects will be enrolled (30 in the drug treatment and 30 in the placebo groups) at 4 study sites: Yale University,the University of California at San Francisco, Children's Hospital of Philadelphia, and the Barbara Davis Diabetes Center.
Interventions
DRUGmAb hOKT3gamma1(Ala-Ala), Teplizumab
This is a randomized, two-arm, double blind placebo controlled phase II trial in which 60 participants with recent-onset T1DM are randomized at a 1:1 ratio to receive Teplizumab or placebo over a 14 day treatment period. The course of Teplizumab comprises daily doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, 413 µg/m2, and 10 of 826 µg/m2.
DRUGPlacebo Arm
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Juvenile Diabetes Research Foundation
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
8 Years to 30 Years
Healthy volunteers
No
Inclusion criteria
* age 8 - 30, * duration of diabetes 4 - 12 months, * weight greater than 27.5 kg, * stimulated C-peptide \>= 0.2 pmol/ml
Exclusion criteria
* asthma, * history of hepatitis C, hepatitis B, HIV
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| C-peptide Area Under the Curve (AUC) Response to a Mixed Meal Tolerance Test (MMTT) at 12 Months | At month 12 post-treatment | C-peptide secretory response was calculated as ln\[(Area Under the Curve of the C-peptide from the 240 minute MMTT/240 +1\] For presentation, the C-peptide data were converted to the AUC as pmol/ml. This is adjusted for baseline. |
| C-peptide Area Under the Curve (AUC) Response to a Mixed Meal Tolerance Test (MMTT) at Baseline | At Baseline (before treatment) | C-peptide secretory response was calculated as ln\[(Area Under the Curve of the C-peptide from the 240 minute MMTT/240 +1\] For presentation, the C-peptide data were converted to the AUC as pmol/ml. This baseline data was used to adjust for the C-peptide AUC primary endpoint measure at 12 months. |
Secondary
| Measure | Time frame |
|---|---|
| Hemoglobin A1c | At 12 months post-treatment |
| Average Insulin Use Over 12 Months | After 12 months post-treatment |
| Baseline Insulin Use | At baseline (before treatment) |
| Baseline Hemoglobin A1c | At baseline (before treatment) |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited from 4 clinical sites and were eligible if they were between the ages of 8-30 and diagnosed with Type 1 Diabetes for at least 4 months, but not more than 12 months prior to enrollment.
Participants by arm
| Arm | Count |
|---|---|
| Saline Infusions (Placebo) The course of normal saline infusion comprises daily doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, 413 µg/m2, and 10 of 826 µg/m2 over a 14 day treatment period. | 27 |
| Teplizumab Infusions (Active) The course of teplizumab infusion comprises daily doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, 413 µg/m2, and 10 of 826 µg/m2 over a 14 day treatment period. | 31 |
| Total | 58 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 3 |
Baseline characteristics
| Characteristic | Saline Infusions (Placebo) | Teplizumab Infusions (Active) | Total |
|---|---|---|---|
| Age, Customized <15 years | 20 participants | 18 participants | 38 participants |
| Age, Customized >=15 years | 7 participants | 13 participants | 20 participants |
| Sex/Gender, Customized Female | 10 participants | 15 participants | 25 participants |
| Sex/Gender, Customized Male | 17 participants | 16 participants | 33 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 29 / 29 | 25 / 34 |
| serious Total, serious adverse events | 0 / 29 | 1 / 34 |
Outcome results
Primary
C-peptide Area Under the Curve (AUC) Response to a Mixed Meal Tolerance Test (MMTT) at 12 Months
C-peptide secretory response was calculated as ln\[(Area Under the Curve of the C-peptide from the 240 minute MMTT/240 +1\] For presentation, the C-peptide data were converted to the AUC as pmol/ml. This is adjusted for baseline.
Time frame: At month 12 post-treatment
Population: This endpoint was compared in the modified intent to treat population which included all subjects with at least one post-randomization mixed meal tolerance test (MMTT)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Teplizumab Infusions (Active) | C-peptide Area Under the Curve (AUC) Response to a Mixed Meal Tolerance Test (MMTT) at 12 Months | 0.451 pmol/ml |
| Saline Infusions (Placebo) | C-peptide Area Under the Curve (AUC) Response to a Mixed Meal Tolerance Test (MMTT) at 12 Months | 0.371 pmol/ml |
Primary
C-peptide Area Under the Curve (AUC) Response to a Mixed Meal Tolerance Test (MMTT) at Baseline
C-peptide secretory response was calculated as ln\[(Area Under the Curve of the C-peptide from the 240 minute MMTT/240 +1\] For presentation, the C-peptide data were converted to the AUC as pmol/ml. This baseline data was used to adjust for the C-peptide AUC primary endpoint measure at 12 months.
Time frame: At Baseline (before treatment)
Population: This endpoint was compared in the modified intent to treat population which included all subjects with at least one post-randomization mixed meal tolerance test (MMTT)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Teplizumab Infusions (Active) | C-peptide Area Under the Curve (AUC) Response to a Mixed Meal Tolerance Test (MMTT) at Baseline | 0.593 pmol/ml |
| Saline Infusions (Placebo) | C-peptide Area Under the Curve (AUC) Response to a Mixed Meal Tolerance Test (MMTT) at Baseline | 0.554 pmol/ml |
Secondary
Average Insulin Use Over 12 Months
Time frame: After 12 months post-treatment
Population: This endpoint was compared in the modified intent to treat population which included all subjects with at least one post-randomization mixed meal tolerance test (MMTT)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Teplizumab Infusions (Active) | Average Insulin Use Over 12 Months | 0.475 U/kg/d |
| Saline Infusions (Placebo) | Average Insulin Use Over 12 Months | 0.574 U/kg/d |
Secondary
Baseline Hemoglobin A1c
Time frame: At baseline (before treatment)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Teplizumab Infusions (Active) | Baseline Hemoglobin A1c | 6.32 percentage of hemoglobin A1c |
| Saline Infusions (Placebo) | Baseline Hemoglobin A1c | 7.1 percentage of hemoglobin A1c |
Secondary
Baseline Insulin Use
Time frame: At baseline (before treatment)
Population: This endpoint was compared in the modified intent to treat population which included all subjects with at least one post-randomization mixed meal tolerance test (MMTT)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Teplizumab Infusions (Active) | Baseline Insulin Use | 0.405 U/kg/d |
| Saline Infusions (Placebo) | Baseline Insulin Use | 0.386 U/kg/d |
Secondary
Hemoglobin A1c
Time frame: At 12 months post-treatment
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Teplizumab Infusions (Active) | Hemoglobin A1c | 6.85 percentage of hemogloblin A1c |
| Saline Infusions (Placebo) | Hemoglobin A1c | 7.35 percentage of hemogloblin A1c |