Summary

Eligibility
for people ages 6-34 (full criteria)
Location
at San Francisco, California and other locations
Dates
study started
completion around
Principal Investigator
by Stephen Gitelman, MD
Headshot of Stephen Gitelman
Stephen Gitelman

Description

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.

Official Title

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

Details

This study has an enrollment period of 4 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.

Keywords

Diabetes Mellitus, Type 1, TrialNet, T1D, Type 1 Diabetes Mellitus, Thymoglobulin, Antilymphocyte Serum, Antithymocyte Globulin, Antithymocyte globulin (ATG)

Eligibility

You can join if…

Open to people ages 6-34

  1. Willing to provide informed consent or have a parent or legal guardian provide informed consent when the subject is <18 years of age.
  2. Age greater than or equal to 6 and < 35 years
  3. At least two or more diabetes-related biochemical autoantibodies (mIAA, GADA, ICA, IA-2A, ZnT8A) present on the same sample. In the absence of other antibodies, ICA and GADA positivity alone will not suffice for eligibility in this trial.
  4. Weight greater than the 5th percentile for age and sex.
  5. BMI < 95th and > 5th percentile for age for those under age 18 years and < 30 and > 15 for adults (≥ 18)
  6. ADA Stage 2 criteria* AND at least one of the following high-risk markers (occurring at the same visit) within 7 weeks (52 days) of randomization, defined below (for defining a 2-year 50% risk for progression to Stage 3 T1D):
    1. HbA1c ≥ 5.7 and <6.5% b. Index60 ≥ 1.4 i. Index60 = 0.3695 × (log fasting C-peptide [ng/mL]) + 0.0165 × 60-min glucose (mg/dL) - 0.3644 × 60-min C-peptide (ng/mL) c. DPTRS ≥ 7.4 DPTRS = (1.57 x log BMI) - (0.06 x age) + (0.81 x glucose sum from 30 to 120 min/100) - (0.85 x C-peptide sum from 30 to 120 min/10) + (0.48 x log fasting C-peptide)

    *Dysglycemia is defined as 2-hr glucose ≥ 140 and <200 mg/dL or fasting glucose ≥ 110 and <126 or 30, 60, or 90 minute glucose ≥ 200 mg/dL from OGTT

  7. All subjects must be CMV and EBV PCR negative within 30 days of randomization and may not have had signs or symptoms of a CMV or EBV-compatible illness lasting longer than 7 days within 30 days of randomization
  8. Seated blood pressure less than 130/80 mmHg for participants ≥ 18 years. For participants < 18 years seated blood pressure less than 95th percentile for age, sex and height.
  9. Be at least 4 weeks from last live immunization

    10. Participants are required to receive non-live influenza vaccination at least 2 weeks

    prior to randomization when vaccine for the current or upcoming flu season is available.

    11. Participants must also have a negative COVID-19 test within 7 days of the first day of

    treatment if otherwise eligible

    12. Willingness to comply with study directed social distancing and protection from

    SARS-Cov-2 infection.

    13. Be willing to forgo vaccines (other than killed influenza) during the 3 months after

    study drug treatment period (Days 0 and 1)

    14. Be up to date on all recommended vaccinations based on age of subject* 15. With the exception of stage 2 T1D, subjects must be healthy, as defined by absence of

    any other untreated diagnoses that the protocol committee deems to be a potential confounder.

    16. If a female participant with reproductive potential, willing to avoid pregnancy

    (abstinence or adequate contraceptive method) through the completion of the study infusions and up to 3 months after study drug administration and undergo pregnancy testing prior to each study visit.

    17. Must be residing or have accommodations within 1 hour of the infusion site during the

    two days of study drug infusions and must be within 1 hour of a medical care facility for 1 day after completion of infusion 2.

    18. Participants must live in a location with rapid access to emergency medical services.

    • Adult participants must be fully immunized. Pediatric participants who have not completed their primary vaccination schedule must receive all vaccinations allowable per the national/country-specific 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. For COVID-19 vaccination, all participants will be strongly encouraged to be up-to-date with COVID-19 vaccine(s) as indicated by country-specific guidelines at least 2 weeks prior to randomization.

You CAN'T join if...

  1. Immunodeficiency or clinically significant chronic lymphopenia: (Leukopenia (< 3,000 leukocytes /μL), neutropenia (<1,500 neutrophils/μL), lymphopenia (<800 lymphocytes/μL), thrombocytopenia (<100,000 platelets/μL).
  2. Hemoglobin less than 13.5 g/dL for adult men and less than 12 g/dL for adult females and less than 11 g/dL for participants under age 18
  3. Active signs or symptoms of acute infection at the time of randomization including SARS-Cov-2.
  4. Uncontrolled autoimmune thyroid disease and/or celiac disease (participants must be well controlled for the previous 6 months).
  5. Evidence of prior or current tuberculosis infection as assessed interferon gamma release assay (QuantiFERON).
  6. Currently pregnant or lactating or anticipate getting pregnant within the study period.
  7. Require use of other immunosuppressive agents including chronic use of systemic steroids.
  8. Evidence of current or past HIV or Hepatitis B or current Hepatitis C infection.
  9. 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.

    10. A history of malignancies other than of skin. 11. Evidence of liver dysfunction with AST or ALT outside of the reference range. 12. Evidence of renal dysfunction with creatinine outside of the reference range. 13. Increased bilirubin (total and direct) outside of the normal limit (Participants with

    documentation of Gilbert's Disease permitted).

    14. Vaccination with a live virus within the last 4 weeks. 15. Current or ongoing use of non-insulin pharmaceuticals that affect glycemic control

    within 7 days of screening

    16. Prior treatment with Teplizumab (either in a previous clinical trial or clinically). 17. Has participated in a clinical trial for diabetes prevention previously and received

    active study agent within 3 months of randomization.

    18. Known allergy to ATG or any product excipient 19. Prior treatment with ATG or known allergy to rabbit-derived products or to any product

    excipient

    20. Prior adverse reactions to heparin. 21. Any condition that in the investigator's opinion may adversely affect study

    participation will be reviewed by the Study Chair to ensure consistency and adjudicate whether or not the subject may compromise the study results

    22. Any screening/baseline laboratory result not otherwise stated out of normal reference

    range and/or medical history that may increase the risk of the subject's participation in this trial.

    23. Previously diagnosed with Stage 3 TID according to ADA criteria (see Appendix 3 for

    Criteria for diagnosis of diabetes)

Locations

  • UCSF accepting new patients
    San Francisco California 94143 United States
  • Stanford University accepting new patients
    Stanford California 94305 United States

Lead Scientist at UCSF

  • Stephen Gitelman, MD
    Dr. Gitelman is a physician scientist involved in studies to determine what causes type 1 diabetes mellitus (T1DM), and in clinical trials to prevent disease development, or preserve beta cell function in those recently diagnosed. To this end, he has been an active investigator in the NIH-sponsored TrialNet and Immune Tolerance Network consortia, and other immunotherapy trials in T1DM.

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Links
TrialNet
ID
NCT04291703
Phase
Phase 2 research study
Study Type
Interventional
Participants
Expecting 101 study participants
Last Updated