Low Dose Antithymocyte Globulin (ATG) to Delay or Prevent Progression to Stage 3 T1D

• Status: Not yet recruiting
• Trial end date: 2026-10-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Treatments: Antilymphocyte Serum; Thymoglobulin

Criteria

Inclusion Criteria:

1. Age > 6 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 (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).

4. Must have at least two of the high-risk markers defined below (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. DPTRS ≥ 7.4

5. 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

6. Be at least 4 weeks from last live immunization

7. 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

8. Be willing to forgo vaccines during the 3 months after study drug treatment period (Days 0 and 1)

9. Be up to date on all recommended vaccinations based on age of subject*

10. 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:

1. 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).

2. Have active signs or symptoms of acute infection at the time of randomization

3. Have evidence of prior or current tuberculosis infection as assessed interferon gamma release assay (QuantiFERON) .

4. Be currently pregnant or lactating, or anticipate getting pregnant within the study period

5. Require use of other immunosuppressive agents including chronic use of systemic steroids

6. Have evidence of current or past HIV or Hepatitis B or current Hepatitis C infection.

7. 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

8. Have a history of malignancies other than of skin

9. Evidence of liver dysfunction with AST or ALT greater than 3 times the upper limits of normal

10. Evidence of renal dysfunction with creatinine greater than 1.5 times the upper limit of normal

11. Vaccination with a live virus within the last 4 weeks

12. Current or ongoing use of non-insulin pharmaceuticals that affect glycemic control within 7 days of screening

13. Active participation in another intervention study in the previous 30 days*

14. Prior treatment with active study agent from a previous clinical trial*

15. Known allergy to ATG

16. Prior treatment with ATG or known allergy to rabbit derived products

17. Any condition that in the investigator's opinion may adversely affect study participation or may compromise the study results

18. 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.