Diabetes Mellitus, Type 1
Conditions
Brief summary
This will be a study conducted as a placebo-controlled, double blind, 1:1 randomized controlled clinical trial testing a Tumor Necrosis Factor Blocker (Anti-TNFα) substance versus placebo in subjects with a 2-year 50% risk of progression to stage 3 T1D across multiple centers. The trial will investigate the ability of Anti-TNFα to prevent or delay progression to Stage 3 T1D in the targeted patient population.
Interventions
DRUGGolimumab
For participants ≥45 kg, 50 mg of golimumab will be administered subcutaneously For participants \<45 kg, the dose of golimumab is 30 mg/m2 to maximum of 50 mg
DRUGPlacebo
Inactive Drug
Sponsors
University of South Florida
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Masking description
Active drug and placebo will be identical in appearance and packaging
Intervention model description
Treatment assignment (active drug: placebo) will be assigned in a parallel, randomized, 1:1 model. Randomization will be conducted using block randomization with variable block sizes with stratification on TrialNet study site and age group (\< 12 years old vs. 12 years old or older).
Eligibility
Sex/Gender
ALL
Age
3 Years to 46 Years
Healthy volunteers
No
Inclusion criteria
Potential participants must meet all of the following inclusion criteria: 1. Age \> 3 and \< 46 years 2. Willing to provide Informed Consent or have a parent or legal guardian provide informed consent if the subject is \<18 years of age 3. At least two or more diabetes-related biochemical autoantibodies insulin (mIAA), glutamic acid decarboxylase antibody (GADA), Islet cytoplasmic antibodies (ICA), islet antigen 2 (IA-2A), zinc transporter 8 (ZnT8A) present on the same sample. Of note, ICA and GADA positivity alone cannot be used to define eligibility in this trial). 4. Must have at least two of the high-risk markers defined below (within 7 weeks (52 days) of screening visit if performed as part of TN01 Pathway to Prevention (PTP) study at time of screening; defining a 50% two-year progression risk): a. Abnormal glucose tolerance: i. 2-hr glucose ≥ 140 and \<200 mg/dL, fasting glucose ≥ 110 and \<126, or 30-, 60-, or 90-minute glucose ≥ 200 mg/dL b. HbA1c ≥ 5.7 c. Index60 ≥ 1.4 d. Diabetes Prevention Trial-Type 1 Risk Score (DPTRS) ≥ 7.4 5. Females of childbearing potential must agree to use abstinence or an effective birth control through the treatment period.( 6. Males able to father children, must agree to use abstinence or an effective birth control during the treatment period. 7. Subjects who are Epstein-Barr virus (EBV) seronegative at screening must be EBV Polymerase chain reaction (PCR) negative within 30 days of randomization and may not have had signs or symptoms of an EBV compatible illness lasting longer than 7 days within 30 days of randomization 8. Be at least 4 weeks from last live immunization 9. Be willing to forgo live vaccines through and 3 months after study drug treatment period 10. Be up to date on all recommended vaccinations based on age of subject and willing to receive killed influenza vaccine when available for current or upcoming season. 11. If prior treatment with active study agent from previous clinical trial, approval of medical monitor and investigator that such prior treatment does not impact risk for current study. 12. Subjects who have met all above criteria must have the qualifying oral glucose tolerance test (OGTT) within 7 weeks (52 days) of randomization and baseline visit.
Exclusion criteria
Potential participants must not meet any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The primary outcome is the elapsed time from random treatment assignment to the development of diabetes (T1D) or time of last contact among those randomized | 6 years | The primary outcome is the elapsed time from random treatment assignment to the development of diabetes (T1D) or time of last contact among those randomized |
Outcome results
None listed