Ensayos clínicos

 Inclusion Criteria

• Must meet all criteria below to receive darTregs infusion
  • Stable liver tests, defined as ALT and either alkaline phosphatase or GGT either within normal limits OR ≤ 1.5 X baseline
  • No detectible circulating EBV or CMV DNA 4 weeks prior to Treg infusion
  • For subjects with hepatitis B virus (HBV), no detectible circulating HBV DNA
• Is eligible to resume IS withdrawal after darTregs infusion if all criteria below are met
  • Subject received at least 100 x 10^6 darTregs
  • ALT and either alkaline phosphatase or GGT remain within normal limits or ≤ 1.5 x baseline after darTregs infusion
  • For subjects with elevated liver tests as defined above, local pathology reading of liver biopsy 6-10 days after darTregs infusion is without AR according to Banff criteria
  • IS withdrawal resumes no later than 14 days after darTregs infusion
  • Site principal investigator determines it is acceptable for the study subject to resume IS withdrawal

Exclusion Criteria

• Any of these criteria are not eligible for study enrollment
  • Transplant for liver disease secondary to hepatitis C or autoimmune disease (e.g. autoimmune hepatitis, primary sclerosing cholangitis, or primary biliary cirrhosis), or Hepatocellular Carcinoma (HCC)
  • Matched at both human leukocyte antigen (HLA)-DR loci to the donor
  • Organ, tissue or cell transplant prior to or after the primary solitary living donor liver transplant
  • For subjects with hepatitis B, detectible hepatitis B virus (HBV) DNA
  • History of malignancy within 5 years of enrollment
    • History of adequately treated in-situ cervical carcinoma and/or skin cancer (basal or squamous cell) will be permitted
  • Serologic evidence of human immunodeficiency 1 or 2 infection
  • Epstein Barr Virus (EBV) seronegativity (EBV naïve) if living donor is EBV seropositive
  • Cytomegalovirus (CMV) seronegativity (CMV naïve) if living donor is CMV seropositive
  • Calculated Glomerular filtration rate (GFR) less than 50 mL/min/1.73m^2 at the time of enrollment
  • An episode of Acute Rejection (AR) within one year of enrollment
  • Systemic illness requiring or likely to require recurrent or chronic immunosuppression (IS) drug use
  • Any chronic condition for which anti-coagulation cannot be safely interrupted for liver biopsy
  • Positive pregnancy test
  • Peripheral blood Tregs <30/μL at screening
  • Participation in any other studies that involved investigational drugs or regimens in the preceding year
  • Any other condition, in the investigator's judgment, that increases the risk of darTregs infusion or prevents safe trial participation
  • Unwilling or unable to adhere to study requirements and procedures
  • Screening liver biopsy with any of the following histological criteria, as determined by the reading of a central pathologist
• Any of these criteria are not eligible for darTregs infusion
  • Diagnosis of AR after initiation of IS withdrawal
  • Any vaccination given within 28 days prior to Treg collection for Treg production
  • Receipt of a vaccination within 14 days prior to Treg infusion
  • Unacceptable darTregs product
  • Positive pregnancy test
  • Clinical evidence of viral syndrome less than 7 days prior to darTregs infusion