Immune Effects of Vedolizumab With or Without Anti-TNF Pre-treatment in T1D

Prior treatment

• Receipt of live vaccine (e.g., varicella, MMR (measles, mumps and rubella), intranasal influenza vaccine) within 6 weeks of randomization.
• Receipt of other vaccines within 3 weeks of baseline treatment.
• Receipt of an immune modulating biologic or investigational drug within 3 months or 5 half-lives before screening visit.
• Use of non-insulin therapies aimed to control hyperglycemia within 30 days of screening visit.

Other illness

• History of severe reaction or anaphylaxis to human, humanized or murine monoclonal antibodies
• History of malignancy or serious uncontrolled cardiovascular, nervous system, pulmonary, renal, or gastrointestinal disease
• History of immunodeficiency
• Recent (within 3 months) serious bacterial, viral, fungal, or other infections
• Pending or positive SARS-CoV-2 test or symptoms of possible COVID-19 illness at baseline treatment visit.
• Serologic evidence of current or past HIV, Hepatitis B, or Hepatitis C.
• Positive QuantiFERON or PPD TB test, history of tuberculosis, or active TB infection.
• Active infection with EBV as defined by real-time polymerase chain reaction (PCR).
• Active infection with CMV as defined by real-time PCR.
• History of other clinically significant autoimmune disease needing chronic therapy with biologics or steroids with the exception of celiac disease and stable thyroid disease.
• Any medical or psychological condition that in the opinion of the principal investigator would interfere with the safe completion of the trial.

Lab values

• Clinically significant liver function abnormalities as defined by ALT or AST\> 1.5 x the upper limit of age-determined normal (ULN).
• Any of the following hematologic abnormalities:
  • White blood count \<3,000/μL or \>14,000/μL
  • Lymphocyte count \<800/μL
  • Platelet count \<75,000 /μL
  • Hemoglobin \<10.0 g/dL
  • Neutrophil count \<1500 cells/μL
• Use of medications known to influence glucose tolerance. Topical, nasal, inhaled corticosteroids acceptable per investigator discretion.

Other

• Females who are pregnant or lactating.

• Males and females 18-45 years of age, inclusive
• Diagnosis of T1D between 21 days and 3 years from screening
• Positive for at least one diabetes-related autoantibody any time since diagnosis, including but not limited to:
  • Glutamate decarboxylase (GAD-65)
  • mIAA, if obtained within 10 days of the onset of exogenous insulin therapy
  • IA-2
  • ZnT8 (Zinc transporter 8)
• Random (non-fasting) C-peptide or peak MMTT stimulated C-peptide ≥ 0.2 pmol/mL.
• Females of child-bearing potential must be willing to use effective birth control from the screening visit through 12 weeks post last dose of study medication.
• Up to date for clinically recommended immunizations including COVID-19 and seasonal influenza vaccine at least 3 weeks prior to baseline treatment.
• Willing to forgo live vaccines 6 weeks prior to baseline treatment visit until 6 weeks following last treatment visit.
• HbA1c ≤ 8.5% at screening
• Willing and able to give informed consent for participation