Immunosuppression Withdrawal for Stable Pediatric Liver Transplant Recipients (iWITH)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Immune Tolerance Network (ITN)
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT01638559
First received: July 9, 2012
Last updated: August 17, 2015
Last verified: August 2015

July 9, 2012
August 17, 2015
August 2012
July 2015   (final data collection date for primary outcome measure)
Proportion of subjects with normal liver biopsy and test results [ Time Frame: 12 months post-immunosuppression (IS) withdrawal ] [ Designated as safety issue: Yes ]
The proportion of participants operationally tolerant, defined as those who successfully withdraw from IS and maintain normal allograft status as assessed by liver biopsy and liver tests 12 months after complete ISW.
Proportion of subjects with normal liver biopsy and test results [ Time Frame: 12 months post-IS withdrawal ] [ Designated as safety issue: Yes ]
The proportion of participants that is operationally tolerant, defined as those who successfully withdraw from IS and maintain normal allograft status as assessed by liver biopsy and liver tests 12 months after complete ISW.
Complete list of historical versions of study NCT01638559 on ClinicalTrials.gov Archive Site
  • Composite of refractory acute rejection (AR), chronic rejection (CR), requirement for retransplantation, or death [ Time Frame: 48 months ] [ Designated as safety issue: Yes ]
    Rate of a composite outcome measure defined as the proportion of participants who develop refractory AR, chronic rejection (CR), undergo retransplantation,or die during study participation.
  • Histologic severity of AR episodes according to Banff criteria [ Time Frame: 48 months ] [ Designated as safety issue: Yes ]
  • Clinical severity of AR episodes assessed by treatment and time necessary to resolve AR or allograft dysfunction [ Time Frame: 48 months ] [ Designated as safety issue: Yes ]
  • Histologic progression determined from the stage of fibrosis at baseline to completion of the study according to the Ishak Severity System [ Time Frame: 48 months ] [ Designated as safety issue: Yes ]
  • Durability of operational tolerance defined as the time from achievement of the primary endpoint to IS reinitiation or to the end of trial participation [ Time Frame: 48 months ] [ Designated as safety issue: No ]
  • Percent of IS dose reduction achieved prior to failing the primary endpoint for any reason [ Time Frame: 24 months ] [ Designated as safety issue: No ]
  • Percent of IS dose reduction in IS dose for those who fail to achieve the primary endpoint [ Time Frame: 24 months ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Immunosuppression Withdrawal for Stable Pediatric Liver Transplant Recipients
Immunosuppression Withdrawal for Stable Pediatric Liver Transplant Recipients

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

Anti-rejection medicines, also known as immunosuppressive drugs, are prescribed to organ transplant recipients to prevent rejection of the new organ. Long-term use of these medicines places transplant recipients at higher risk of serious infections and certain types of cancer.

This study seeks to:

  • Find out if it is safe to slowly reduce and then completely stop the immunosuppression taken by children who have received liver transplants. This process is called 'immunosuppression withdrawal'or ISW.
  • Find blood or liver biopsy tests that can help transplant doctors in the future to predict if it is safe to decrease or stop immunosuppression drugs in children who have had a liver transplant.
Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Liver Transplant Recipients
  • Liver Transplantation
  • Immunosuppression
Other: Immunosuppression withdrawal
Participants will undergo gradual ISW in no less than 36 weeks and no more than 52 weeks with frequent monitoring of liver tests. All participants will be followed for 48 months ensuring a minimum of 36 months of follow-up after successful ISW.
Other Name: ISW
Experimental: Immunosuppression withdrawal
Gradual withdrawal of immunosuppressive medication
Intervention: Other: Immunosuppression withdrawal

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
88
July 2017
July 2015   (final data collection date for primary outcome measure)

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 AR or 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.
Both
up to 18 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada
 
NCT01638559
DAIT iWITH, 5U01AI100807-04, RTB-001
Yes
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Allergy and Infectious Diseases (NIAID)
  • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
  • Immune Tolerance Network (ITN)
Principal Investigator: S Feng, M.D. , Ph.D. University of California, San Francisco
Study Chair: J Bucuvalas, M.D. Children's Hospital Medical Center, Cincinnati
National Institute of Allergy and Infectious Diseases (NIAID)
August 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP