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Immunosuppression Withdrawal for Stable Pediatric Liver Transplant Recipients (iWITH)

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ClinicalTrials.gov Identifier: NCT01638559
Recruitment Status : Active, not recruiting
First Posted : July 11, 2012
Results First Posted : June 8, 2017
Last Update Posted : June 8, 2017
Information provided by (Responsible Party):

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

Condition or disease Intervention/treatment Phase
Liver Transplant Recipients Liver Transplantation Immunosuppression Drug: Immunosuppression withdrawal Phase 2

Detailed Description:

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.

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 88 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Immunosuppression Withdrawal for Stable Pediatric Liver Transplant Recipients
Study Start Date : August 2012
Primary Completion Date : March 2016
Estimated Study Completion Date : May 28, 2018

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: Immunosuppression withdrawal
Gradual withdrawal of immunosuppressive treatment withdrawal as per protocol.
Drug: 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

Outcome Measures

Primary Outcome Measures :
  1. Number of Operationally Tolerant Participants [ Time Frame: 12 Months after Complete immunosuppression withdrawal ]
    The number of participants that are operationally tolerant, defined as those who successfully withdraw from immunosuppression and maintain normal allograft status as assessed by liver biopsy and liver tests 12 months after complete immunosuppression withdrawal.

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01638559

United States, California
University of California
San Francisco, California, United States, 94143-0780
United States, Colorado
Children's Hospital of Colorado
Aurora, Colorado, United States, 80045
United States, Georgia
Emory University and Children's Hospital of Atlanta
Atlanta, Georgia, United States, 30322
United States, Illinois
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, United States, 60614
United States, Michigan
University of Michigan C. S. Mott Children's Hospital
Ann Arbor, Michigan, United States, 94143
United States, Missouri
St. Louis Children's Hospital - Washington University
Saint Louis, Missouri, United States, 63110
United States, New York
New York Presbyterian Morgan Stanley Children's Hospital - Columbia University Medical Center
New York, New York, United States, 10032
United States, Ohio
Cincinnati Children's Hospital
Cincinnati, Ohio, United States, 45229
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15224
United States, Texas
Texas Children's Hospital
Houston, Texas, United States, 77030
Canada, Ontario
The Hospital for Sick Children
Toronto, Ontario, Canada, M5G1X8
Sponsors and Collaborators
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
More Information

Additional Information:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT01638559     History of Changes
Other Study ID Numbers: DAIT iWITH
5U01AI100807-04 ( U.S. NIH Grant/Contract )
RTB-001 ( Other Identifier: DAIT NIAID )
First Posted: July 11, 2012    Key Record Dates
Results First Posted: June 8, 2017
Last Update Posted: June 8, 2017
Last Verified: May 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: The plan, upon completion of the study, is to share data in ImmPort [https://immport.niaid.nih.gov/ ], a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts.

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
liver transplant
allograft function
immunosuppression withdrawal