No Placebo Group
Every participant receives an active treatment — no one gets a placebo.
Prior Safety Data
This treatment has already been tested in at least one earlier human trial.
Ready to participate?
Review the details below, then apply to join this clinical trial.
At a Glance
Age
4 – 34
Sex
Any
Trial phase
Phase 2
Study type
Interventional
Purpose
Prevention
Participants needed
60 (estimated)
Sponsor
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) · NIH
Who this trial is looking for
This trial is looking for people aged 4 to 34 who have early signs of Type 1 diabetes. Participants will receive either two infusions of ATG or 14 infusions of teplizumab and will be followed for up to 9 years.
Are You a Good Fit for This Trial?
Rules you outStage 3 Type 1 diabetes
You may be able to join if
I am between 4 and 34 years old.
I have at least two diabetes-related autoantibodies.
I have been tested and meet the criteria for stage 2 Type 1 diabetes.
I am willing to provide informed consent.
If I am under 18, my parent or guardian can provide consent.
I have no active CMV or EBV infection.
I live near the infusion site.
I can avoid pregnancy or get pregnancy tests if I am female.
You may not be able to join if
I have an immune system problem.
I have signs of any infection right now.
I am pregnant or breastfeeding.
I have uncontrolled autoimmune diseases.
I have a serious problem with my blood counts.
I have had certain infections like TB.
I have liver or kidney dysfunction.
I have a history of malignancies other than skin cancer.
Summarized in plain language from this trial's official eligibility criteria.
The full criteria are further down this page — only the research team can
confirm whether you qualify.
Think this trial could be right for you?
Answer three quick questions written from this study's own rules to see if you may qualify. No account needed to find out.
This is a 2-arm, multi-center, open label study to learn if ATG works the same or better than teplizumab in delaying or preventing Stage 3 Type 1 diabetes. Participants will be administered either 2 infusions of ATG or 14 infusions of teplizumab and will then be followed for at least 12-48 months after administration, depending on timepoint enrolled into the study. If the primary endpoint demonstr…
This is a 2-arm, multi-center, open label study to learn if ATG works the same or better than teplizumab in delaying or preventing Stage 3 Type 1 diabetes. Participants will be administered either 2 infusions of ATG or 14 infusions of teplizumab and will then be followed for at least 12-48 months after administration, depending on timepoint enrolled into the study. If the primary endpoint demonstrates a positive signal and as decided by TrialNet, there is potential for a study extention. This would extend follow-up visits for a possible study duration of about 9 years among the earliest enrollees of the initial study.
Trial Locations
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Status
Eligibility Criteria
Inclusion Criteria:
* Willing to provide informed consent or have a parent or legal guardians provide informed consent when the participant is \<18 years of age.
* Aged ≥4 to \<35 years
* A history of at least two or more diabetes-related biochemical autoantibodies (mIAA, GADA, ICA, IA-2A, ZnT8A) p…
Inclusion Criteria:
* Willing to provide informed consent or have a parent or legal guardians provide informed consent when the participant is \<18 years of age.
* Aged ≥4 to \<35 years
* A history of 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.
* Participants must meet ADA stage 2 T1D glycemic criteria\* by TrialNet testing within 100 days of the baseline visit.
\*The ADA definition of stage 2 T1D is characterized by glucose intolerance or dysglycemia in the presence of two or more islet autoantibodies, impaired fasting glucose (≥ 100mg/dL), impaired glucose tolerance (2-hour post 75g glucose load ≥ 140mg/dL), high glucose levels at intermediate time points on OGTT (30, 60, 90 min timepoints of ≥ 200 mg/dL), and/or HbA1c between 5.7% and 6.4% or ≥ 10% increase in HbA1c within a two year window, with the most recent HbA1c value obtained within 100 days of the baseline visit.
* Participants, regardless of serostatus, must meet all of the following:
* Be EBV and CMV PCR negative prior to randomization
* Be EBV and CMV PCR negative within 2 weeks prior to the baseline visit
* Have no signs or symptoms of a CMV or EBV-compatible illness lasting longer than 7 days within 30 days prior to the baseline visit.
* Be at least 8 weeks from last live immunization at the time of the baseline visit.
* Be willing to forgo vaccines (other than non-live influenza and COVID-19) during the 3 months after study drug treatment period and forgo live vaccines for 12 months after study drug treatment period.
* Must meet TrialNet eligibility minimum immunization recommendations found in Appendix A of the manual of operations (MOO).
* With the exception of stage 2 T1D, participants must be healthy, as defined by absence of any other untreated diagnoses that the investigator deems to be a potential confounder.
* 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.
* Must be residing or have accommodations within 1 hour of the infusion site during study drug infusions and must be within 1 hour of a medical care facility for 1 day after completion of infusions.
* Participants must live in a location with rapid access to emergency medical services.
Exclusion Criteria:
* Immunodeficiency or clinically significant chronic lymphopenia: (Leukopenia (\<3,000 leukocytes/μL), neutropenia (\<1,500 neutrophils/μL), lymphopenia (\<1000 lymphocytes/μL), thrombocytopenia (\<150,000 platelets/μL).
* Hemoglobin less than 13 g/dL for adult men and less than 11.5g/dL for adult females and less than 11 g/dL for participants under age 18.
* Active signs or symptoms of acute or chronic infection at the time of the baseline visit including SARS-Cov-2.
* Uncontrolled autoimmune thyroid disease and/or celiac disease (participants must be well controlled for the previous 6 months).
* Evidence of prior or current tuberculosis infection through any one or more of the following:
1. A history of latent or active TB
2. Signs and/or symptoms of TB
3. Recent close contact with a person with known or suspected active TB unless appropriate prophylaxis for TB was given
4. A history of a chest X-ray consistent with active TB or old, inactive TB, or interferon gamma release assay IGRA (QuantiFERON) test
5. A history of a positive purified protein derivative (PPD) skin test result (\>10 mm induration), or positive/repeatedly indeterminate on an interferon-gamma release assay (IGRA; e.g., QuantiFERON-TB test).
* Currently pregnant or lactating or anticipate getting pregnant within the study period.
* Require use of other immunosuppressive agents including chronic use of oral or intravenous injectable steroids.
* Evidence of current or past HIV or Hepatitis B or current Hepatitis C infection.
* 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, Down syndrome, adrenal insufficiency, neurological disease, or blood count abnormalities.
* A history of malignancies other than of skin.
* Evidence of liver dysfunction with AST or ALT ≥ 2 times the upper limit of the reference range.
* Evidence of renal dysfunction with creatinine ≥ 1.5 times the upper limit of the reference range.
* Increased bilirubin ≥ 2 times (total) or ≥ 1.5 times (direct) the normal limit (Participants with documentation of Gilbert's Disease permitted).
* Vaccination with a live vaccine within the last 8 weeks or killed/inactivated vaccine within the last 2 weeks of the baseline visit.
* Current or ongoing use of non-insulin pharmaceuticals that affect glycemic control within 14 days of screening.
* Prior treatment with Teplizumab or ATG (either in a previous clinical trial or clinically).
* Has previously participated in a clinical trial for diabetes prevention and received active study agent within 6 months of treatment.
* Known allergy to rabbits or rabbit derived products.
* Prior adverse reactions to heparin.
* Any condition that in the investigator's opinion may adversely affect study participation.
* Any screening/baseline laboratory result not otherwise stated out of normal reference range and/or medical history that may increase the risk of the participant's participation in this trial.
* Previously diagnosed with Stage 3 TID according to ADA criteria.
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