Platform Trial to Delay Stage 3 Diabetes: Comparing Teplizumab With ATG

Korábbi kezelés

• 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:
  • A history of latent or active TB
  • Signs and/or symptoms of TB
  • Recent close contact with a person with known or suspected active TB unless appropriate prophylaxis for TB was given
  • A history of a chest X-ray consistent with active TB or old, inactive TB, or interferon gamma release assay IGRA (QuantiFERON) test
  • 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).
• Require use of other immunosuppressive agents including chronic use of oral or intravenous injectable steroids.
• Vaccination with a live vaccine within the last 8 weeks or killed/inactivated vaccine within the last 2 weeks of the baseline visit.
• 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.
• Prior adverse reactions to heparin.
• Previously diagnosed with Stage 3 TID according to ADA criteria.

Más betegség

• Active signs or symptoms of acute or chronic infection at the time of the baseline visit including SARS-Cov-2.
• Evidence of current or past HIV or Hepatitis B or current Hepatitis C infection.
• A history of malignancies other than of skin.
• Known allergy to rabbits or rabbit derived products.
• Any condition that in the investigator's opinion may adversely affect study participation.

Laborértékek

• 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.
• 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.
• 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).
• 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.

Egyéb

• Currently pregnant or lactating or anticipate getting pregnant within the study period.
• Current or ongoing use of non-insulin pharmaceuticals that affect glycemic control within 14 days of screening.

• 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.