Early Signals of the Transition From Immune Quiescence to Activation in the Liver Allograft Microenvironment and in the Circulation

NCT07549503 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: DAIT RTB-018
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 10

Brief Summary

This is a prospective multi-center, longitudinal study to determine efficacy of 50 percent Immunosuppression (IS) reduction. One hundred fully eligible participants will reduce IS by 50 percent in two steps. Liver tests will be checked every 0.5 months through month 4, once a month through month 12, and every other month through month 18. Liver transplant (LTx) center visits will take place at screening, months 6, 12 and 18 after initiating IS dose reduction. A protocol driven liver biopsy to adjudicate the endpoint will be performed at 18 months. The duration of the study from time of starting IS dose reduction to the primary endpoint assessment is 18 months. The primary objective is to assess the efficacy of 50 percent IS dose reduction in children with Liver transplants (LTxs)

Conditions

Liver Transplant

Keywords

Liver transplant; Immunosuppression

Outcome Measures

Primary Outcomes (1)

• Achieving successful 50 percent Immunosuppression (IS) reduction

  Defined as meeting both biochemical and histological criteria of stability

  At 18 months

Secondary Outcomes (4)

• Clinical severity of Acute rejection (AR) episodes

  At 18 months

• Histological severity of Acute rejection (AR) episodes

  At 18 months

• The proportion of participants who experience Acute rejection (AR)

  At 18 months

• Achieving clinically successful 50 percent Immunosuppression (IS) reduction

  At 18 months

Other Outcomes (13)

• EXPLORATORY: The association between donor specific antibody (DSA) status and the outcome of 50 percent Immunosuppression (IS) dose reduction

  At 18 months

• EXPLORATORY: The association between the degree of molecular mismatch and the outcome of 50 percent Immunosuppression (IS) dose reduction

  At 18 months

• EXPLORATORY: The association between the degree of molecular mismatch and the development of de novo donor specific antibody (DSA)

  At 18 months

Study Arms (1)

IS dose reduction

EXPERIMENTAL

Eligible participants will reduce immunosuppression (IS) by 50 percent in two steps. For subjects taking tacrolimus once daily: 1. reduce dose to 75 percent of initial dose for 6 weeks 2. reduce dose to 50 percent of initial dose For subjects taking tacrolimus twice daily: 1. reduce evening such that the total daily dose is 75 percent of the initial dose for 6 weeks 2. stop evening dose For participants taking different doses of tacrolimus in the morning and evening, the clinical site will confer will the protocol chair and PI to determine the schedule for IS reduction

Procedure: Tacrolimus reduction

Interventions

Tacrolimus reduction PROCEDURE

Prospective multi-center, longitudinal study to determine the success rate of 50% immunosuppression (IS) dose reduction. One hundred fully eligible participants will reduce IS by 50% in two steps

IS dose reduction

Eligibility Criteria

• Age: 3 Years - 13 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Participant and parent or guardian must be able to understand and provide informed assent and consent, respectively
• Recipient of a living or deceased donor Liver transplant (LTx) at \<7 years of age
• \> 3 years but \<7 years after LTx at the time of study enrollment
• Stable liver tests defined as baseline serum alanine aminotransferase (ALT) level \< 30 IU/l and gamma-glutamyl transferase (GGT) level \< 50 IU/l (based on the average of the 3 most recent values prior to screening; all must be within 1 year of screening; 2 must be within 6 months of screening)
• No Acute rejection (AR) or chronic rejection within 12 months of enrollment
• Tacrolimus monotherapy for \> 6 months with baseline 12-hour trough levels \<8 ng/mL (based on the average of 3 values prior to screening; all must be within 1 year of screening; 2 must be within 6 months of screening)
• Participants of childbearing potential must have a negative pregnancy test upon study entry

You may not qualify if:

• Liver transplant (LTx) for autoimmune disease, including autoimmune hepatitis or primary sclerosing cholangitis
• LTx for hepatitis B or hepatitis C
• Recipient of any other organ transplant or liver re-transplant, except for patients who have a repeat LTx within 30 days of first LTx who are eligible for enrollment
• \>=50 percent dose increase in tacrolimus within 12 months of enrollment
• Discontinued a second Immunosuppression (IS) agent within 12 months of enrollment
• Systemic illness requiring chronic or recurrent use of IS for which there is a risk of reactivation if tacrolimus is reduced
• Use of medication to treat systemic conditions which in the judgement of the investigator could influence results of the study
• Active or chronic infection requiring treatment
• Inability or unwillingness to comply with the study protocol
• Use of investigational drug within 4 weeks (or 5 half-lives of investigational drug, whichever is longer) of enrollment
• Has any condition that, in the opinion of the investigator, will interfere with safe participation in the trial

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (10)

UCSF Benioff Children's Hospital

San Francisco, California, 94143, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

Emory University School of Medicine/Children's Healthcare of Atlanta

Atlanta, Georgia, 30307, United States

Location

Ann and Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Cincinnati Children's Hospital

Cincinnati, Ohio, 45229, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 15224, United States

Location

Monroe Carell Jr. Children's Hospital at Vanderbilt

Nashville, Tennessee, 37232, United States

Location

Related Links

• Division of Allergy, Immunology, and Transplantation
• National Institute of Allergy and Infectious Diseases

Study Officials

• Sandy Feng, MD, Ph.D.

  University of California San Francisco School of Medicine: Transplantation

  STUDY CHAIR

• John Bucuvalas, M.D.

  Icahn School of Medicine at Mount Sinai: Transplantation

  STUDY CHAIR

Central Study Contacts

Ada Chao

CONTACT

415-353-7004; ada.chao@ucsf.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 16, 2026
• First Posted: April 24, 2026
• Study Start: May 8, 2026
• Primary Completion (Estimated): April 1, 2031
• Study Completion (Estimated): October 1, 2031
• Last Updated: April 24, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (10)