Immunosuppression Withdrawal for Stable Pediatric Liver Transplant Recipients

• Status: Completed
• Trial end date: 2018-06-11
• Target enrollment: 0
• Participant gender: All

Summary

The primary objective of this study is to assess the efficacy of immunosuppression withdrawal (ISW) in pediatric liver transplant (tx) recipients.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Immune Tolerance Network (ITN); National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Criteria

Inclusion Criteria:

• Subject and/or parent guardian must be able to understand and provide informed consent;

• Is the recipient of a living or deceased donor liver tx when subject was less than or equal to 6 years of age;

• Is at least 4 years post-tx at the time of study enrollment;

• Has normal allograft function defined as Alanine aminotransferase (ALT) < 50 IU/l and gamma-glutamyl transferase (GGT) < 50 IU/l;

• Has no evidence of acute rejection (AR) or chronic rejection (CR) within the past 2 years, based on medical history;

• Is stable on IS monotherapy with a calcineurin inhibitor (CNI);

• For female subjects of childbearing potential, subject must have a negative pregnancy test upon study entry;

• For female and male subjects with reproductive potential, subject must agree to use FDA approved methods of birth control for the duration of the study;

• Must be negative for hepatitis B virus (HBV) and hepatitis C virus (HCV) infection within one year of enrollment;

• Must have screening biopsy that fulfills, based on central pathology reading, the following criteria:

• Portal inflammation and interface activity: Preferably absent, but minimal to focal mild portal mononuclear inflammation may be present. Interface necro-inflammatory activity is absent or equivocal/minimal and, if present, involves a minority of portal tracts.

• Centrizonal/peri-venular inflammation: Preferably absent, but minimal to focal mild perivenular mononuclear inflammation may be present. Perivenular necro-inflammatory activity is absent or equivocal/minimal and, if present, involves a minority of terminal hepatic venules.

• Bile duct changes: No lymphocytic bile duct damage, ductopenia and biliary epithelial senescence changes, unless there is an alternative, non-immunologic explanation (e.g. biliary strictures).

• Fibrosis: < Ishak Stage 3 (i.e. not more than occasional portal-to-portal bridging). Perivenular fibrosis should be less than "moderate", according to Banff Criteria.

• Arteries: Negative for obliterative or foam cell arteriopathy.

Exclusion Criteria:

• Have received a liver tx for autoimmune liver disease, including autoimmune hepatitis or primary sclerosing cholangitis;

• Have received a liver tx for hepatitis B or hepatitis C;

• Have received a second organ transplant before, simultaneously, or after liver tx;

• Have a calculated glomerular filtration rate (modified Schwartz formula) of less than 60 mL/min/1.73 m^2;

• Have had a 50 percent (%) dose increase in CNI within 6 months of screening;

• Have discontinued a second IS agent within 12 months of screening;

• Have any systemic illness requiring or likely to require chronic or recurrent use of IS;

• Is pregnant or breastfeeding;

• Is unwilling or unable to adhere with study requirements and procedures;

• Have mental illness or history of drug or alcohol abuse that, in the opinion of the investigator, would interfere with the participant's ability to comply with study requirements;

• Is unwilling or unable to provide consent or comply with the study protocol;

• Has used investigational drugs within 4 weeks of enrollment;

• Is receiving treatment for HIV infection;

• Has received any licensed or investigational live attenuated vaccine(s) within two months of enrollment;

• Has any medical condition that, in the opinion of the investigator, will interfere with safe participation in the trial.