Autoantibody Positive, Non-diabetic Relatives at Risk for Type 1 Diabetes, High Risk, Impaired Glucose Tolerance
Conditions
Keywords
type 1 diabetes, pre-diabetic, autoantibody positive, at risk for type 1 diabetes, glucose intolerance, relatives of people with type 1 diabetes
Brief summary
The study will determine whether the anti-CD3 monoclonal antibody, teplizumab, can help to prevent or delay the onset of type 1 diabetes (T1D) in relatives determined to be at very high risk for developing the disease. Teplizumab has been studied in new onset type 1 diabetes for testing of efficacy and safety in previous studies; other studies are currently in progress. The results of previous studies indicate that teplizumab reduces the loss of insulin production during the first year after diagnosis in individuals with type 1 diabetes. The purpose of this study is to determine if teplizumab can interdict the immune process that causes the destruction of insulin secreting beta cells in the pancreas during the pre-diabetic state and thereby prevent or delay the onset of type 1 diabetes.
Detailed description
The study plans to enroll approximately 71 subjects between the ages of 8-45 years, over 2-3 years. The study is projected to last between 4-6 years, depending upon rate of enrollment and number of subjects who develop diabetes. The main study objective is to determine whether intervention with teplizumab will prevent or delay the development of type 1 diabetes in high risk autoantibody positive non-diabetic relatives of individuals with T1D. Secondary outcomes are to include analyses of C-peptide and other measures from Oral Glucose Tolerance Testing (OGTT), safety, tolerability, and other mechanistic outcomes will be assessed during the study.
Interventions
DRUGTeplizumab
intravenous infusions
DRUGPlacebo infusion
Placebo for Teplizumab
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Center for Research Resources (NCRR)
Juvenile Diabetes Research Foundation
American Diabetes Association
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
8 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
* Between ages of 8-45 years * Have a relative with type 1 diabetes * If first degree relative must be 8-45 years old (brother, sister, parent, offspring) * If second degree relative must be between 8-20 years old (niece, nephew, aunt, uncle, grandchild, cousin) * Abnormal glucose tolerance by OGTT confirmed with 7 weeks of baseline visit \[fasting blood glucose greater than 110mg/dL or and less than 126 mg/dL OR 2 hour glucose greater or equal to 140 mg/dL and less than 200 mg/dL OR 30, 60, or 90 minute value on OGTT greater than or equal to 200 mg/dL\] * Presence of at least two confirmed diabetes autoantibodies
Exclusion criteria
* type 1 diabetes previously diagnosed or detected at screening \[fasting glucose greater or equal to 126 mg/dL or 2 hour glucose greater or equal to 200 mg/dL\] * abnormalities in blood counts, liver enzymes, international normalised ratio (INR), * positive purified protein derivative (PPD) test * vaccination with live virus within 6 weeks of randomization * evidence of acute infection based on laboratory testing or clinical evidence * serological evidence of past current or past HIV , hepatitis B, or hepatitis C infection * Be currently pregnant or lactating * Prior treatment with study drug * Prior treatment with other monoclonal antibody in past one year
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of New Diabetes Per Year | During follow-up, median 745 days, range 74 to 2683 | Rate at which criteria are met for diabetes onset as defined by the American Diabetes Association (ADA) based on glucose testing or the presence of unequivocal hyperglycemia with acute metabolic decompensation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | Baseline Visit to Diagnosis of Type 1 Diabetes median 745 days, range 74 to 2683 | Adverse events categorized and graded via CTCAE. |
Countries
Canada, Germany, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Teplizumab Intravenous infusions of teplizumab given for 14 consecutive days. Each infusion takes about 30 minutes and is followed by a 2 hour observation period.
Teplizumab: intravenous infusions | 44 |
| Placebo Infusion Intravenous infusion of placebo (saline) will be given for 14 consecutive days. Infusions will take approximately 30 minutes and will be followed by a two hour observation period.
Placebo infusion: Placebo for Teplizumab | 32 |
| Total | 76 |
Baseline characteristics
| Characteristic | Teplizumab | Placebo Infusion | Total |
|---|---|---|---|
| Age, Continuous | 14 years | 13 years | 13.9 years |
| Autoantibodies Positive Anti-GAD65 harmonized | 40 Participants | 28 Participants | 68 Participants |
| Autoantibodies Positive Anti-IA-2 harmonized | 27 Participants | 24 Participants | 51 Participants |
| Autoantibodies Positive Anti-ZnT8 | 32 Participants | 24 Participants | 56 Participants |
| Autoantibodies Positive Islet Cell Cytoplasmic Autoantibodies (ICA) | 29 Participants | 28 Participants | 57 Participants |
| Autoantibodies Positive Micro insulin | 20 Participants | 11 Participants | 31 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 43 Participants | 31 Participants | 74 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Glycated hemoglobin level | 5.2 percentage of glycated hemoglobin | 5.3 percentage of glycated hemoglobin | 5.2 percentage of glycated hemoglobin |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 44 Participants | 30 Participants | 74 Participants |
| Relationship to person with type 1 diabetes Identical twin | 4 Participants | 0 Participants | 4 Participants |
| Relationship to person with type 1 diabetes Offspring | 6 Participants | 6 Participants | 12 Participants |
| Relationship to person with type 1 diabetes Parent | 6 Participants | 3 Participants | 9 Participants |
| Relationship to person with type 1 diabetes Second degree relative | 2 Participants | 3 Participants | 5 Participants |
| Relationship to person with type 1 diabetes Sibling and another first degree relative | 2 Participants | 3 Participants | 5 Participants |
| Relationship to person with type 1 diabetes Sibling(s) | 24 Participants | 16 Participants | 40 Participants |
| Relationship to person with type 1 diabetes Third degree relative or further removed | 0 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Female | 19 Participants | 15 Participants | 34 Participants |
| Sex: Female, Male Male | 25 Participants | 17 Participants | 42 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 44 | 0 / 32 |
| other Total, other adverse events | 43 / 44 | 23 / 32 |
| serious Total, serious adverse events | 8 / 44 | 1 / 32 |
Outcome results
Primary
Rate of New Diabetes Per Year
Rate at which criteria are met for diabetes onset as defined by the American Diabetes Association (ADA) based on glucose testing or the presence of unequivocal hyperglycemia with acute metabolic decompensation.
Time frame: During follow-up, median 745 days, range 74 to 2683
Population: Relatives of patients with type 1 diabetes who did not have diabetes but were at high risk for development of clinical disease.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Teplizumab | Rate of New Diabetes Per Year | 43 N diabetes per 100 participant years |
| Placebo Infusion | Rate of New Diabetes Per Year | 72 N diabetes per 100 participant years |
Secondary
Number of Participants With Adverse Events
Adverse events categorized and graded via CTCAE.
Time frame: Baseline Visit to Diagnosis of Type 1 Diabetes median 745 days, range 74 to 2683
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Teplizumab | Number of Participants With Adverse Events | 43 Participants |
| Placebo Infusion | Number of Participants With Adverse Events | 23 Participants |