TN28: Low Dose Antithymocyte Globulin (ATG) to Delay or Prevent Progression to Stage 3 T1D
Study Details
Study Description
Brief Summary
A multi-center, placebo-controlled, double blind, 2:1 randomized control clinical trial testing low-dose ATG vs. placebo in subjects with a 2 year 50% risk of progression to stage 3 T1D.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
This study has an enrollment period of three years and once the enrollment phase has concluded, an additional two years of follow-up visits will be conducted for all participants. Participants enrolled in the first year of the study can expect to complete follow-up visits for approximately four additional years if progression to stage 3 (Type 1 Diabetes Onset) does not occur. Participant follow-up visits after the treatment phase of the study includes general assessments (medical history, physical exam, medications and adverse events) and laboratory assessments to determine current health status and glucose tolerance.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Antithymocyte globulin (ATG) Antithymocyte globulin (ATG) will be intravenously administered over two days, with a total of 2 infusion periods. The first infusion is given at baseline visit (day 1), the second is given the next day at baseline visit (day 2). Body weight at baseline (Day 0- admission for the ATG/placebo infusion) will be used in calculating the doses for all infusions. The first dose (0.5mg/kg) will be infused over a minimum of 4 hours, and the second dose (2mg/kg) over a minimum of 4 hours with a maximum infusion time for each infusion of 10 hours. The second dose should be given no less than 12 and no more than 24 hours after completion of the previous dose. The final prepared product is to be labeled to protect the blind. Infusions may be administered either in a hospital or outpatient setting at the investigator's or institutions discretion. |
Drug: Antithymocyte Globulin
Thymoglobulin
Other Names:
|
| Placebo Comparator: Placebo 0.9% Sodium Chloride Injection USP ("Normal" saline) is to be dispensed as the placebo for this study. The placebo is to be prepared dispensing an infusion bag of 0.9% Sodium Chloride Injection USP ("Normal" saline) with no additives (no ATG, no premedications) and label the product to protect the blind. The placebo will also be administered over a minimum of 4 hours for the first and second doses with a maximum infusion time of 10 hours. The second dose of the placebo arm should be given no less than 12 and no more than 24 hours after completion of the previous dose. Infusions may be administered either in a hospital or outpatient setting at the investigator's or institutions discretion. |
Drug: Placebo (for ATG)
Normal Saline administered by IV infusion to mimic ATG
|
Outcome Measures
Primary Outcome Measures
- Progression to Stage 3 T1D [5 years]
The primary outcome is the elapsed time from random treatment assignment to the development of diabetes or time of last contact among those randomized
Eligibility Criteria
Criteria
Inclusion Criteria:
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Age > 6 and < 46 years
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Willing to provide Informed Consent or have a parent or legal guardian provide informed consent if the subject is <18 years of age
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At least two or more diabetes-related biochemical autoantibodies (mIAA, GADA, ICA, IA-2A, ZnT8A present on the same sample. Of note, ICA and GADA positivity alone cannot be used to define eligibility in this trial).
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Must have at least two of the high-risk markers defined below (defining a 50% two year progression risk):
- 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. DPTRS ≥ 7.4
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Subjects who are EBV seronegative at screening must be EBV 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
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Be at least 4 weeks from last live immunization
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Participants are required to receive killed influenza vaccination at least 2 weeks prior to randomization when vaccine for the current or upcoming flu season is available
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Be willing to forgo vaccines during the 3 months after study drug treatment period (Days 0 and 1)
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Be up to date on all recommended vaccinations based on age of subject*
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Subjects who have met all above criteria must have a non-diabetic OGTT performed within 100 days of randomization.
- Adult subjects must be fully immunized. Pediatric subjects who have not completed their primary vaccination schedule must receive all vaccinations allowable per the AAP immunization guidelines for their current age prior to study drug delivery. Any remaining vaccinations should be given and continue per the schedule at least 3 months after study drug is administered.
Exclusion Criteria:
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Be immunodeficient or have clinically significant chronic lymphopenia: (Leukopenia (< 3,000 leukocytes /μL), neutropenia (<1,500 neutrophils/μL), lymphopenia (<800 lymphocytes/μL), or thrombocytopenia (<100,000 platelets/μL).
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Have active signs or symptoms of acute infection at the time of randomization
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Have evidence of prior or current tuberculosis infection as assessed interferon gamma release assay (QuantiFERON) .
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Be currently pregnant or lactating, or anticipate getting pregnant within the study period
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Require use of other immunosuppressive agents including chronic use of systemic steroids
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Have evidence of current or past HIV or Hepatitis B or current Hepatitis C infection.
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Have any complicating medical issues or abnormal clinical laboratory results that may interfere with study conduct, or cause increased risk to include pre-existing cardiac disease, COPD, sickle cell disease, neurological disease, or blood count abnormalities
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Have a history of malignancies other than of skin
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Evidence of liver dysfunction with AST or ALT greater than 3 times the upper limits of normal
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Evidence of renal dysfunction with creatinine greater than 1.5 times the upper limit of normal
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Vaccination with a live virus within the last 4 weeks
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Current or ongoing use of non-insulin pharmaceuticals that affect glycemic control within 7 days of screening
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Active participation in another intervention study in the previous 30 days*
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Prior treatment with active study agent from a previous clinical trial*
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Known allergy to ATG
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Prior treatment with ATG or known allergy to rabbit derived products
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Any condition that in the investigator's opinion may adversely affect study participation or may compromise the study results
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Previously diagnosed with TID according to ADA criteria
- Potential participants who participated in a previous clinical trial will require review and approval by the protocol committee and/or TrialNet medical monitor before screening for this protocol.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- TrialNet TN28
- UC4DK117009