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

Early Signals of the Transition From Immune Quiescence to Activation in the Liver Allograft Microenvironment and in the Circulation (RTB-018)

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)

Study Overview

• Status: Not yet recruiting
• Conditions: Liver Transplant
• Intervention / Treatment: Procedure: Tacrolimus reduction

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ada Chao; Phone Number: 415-353-7004; Email: ada.chao@ucsf.edu

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • UCSF Benioff Children's Hospital
      • Contact: Paige Shave; Phone Number: 415-514-1170; Email: Paige.shave@ucsf.edu
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado
      • Contact: Michelle Landis; Email: Michelle.landis@childrenscolorado.org
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20007
      • MedStar Georgetown University Hospital
      • Contact: Iryna Asipenka; Email: Iryna.M.Asipenka@medstar.net
  • Georgia
    • Atlanta, Georgia, United States, 30307
      • Emory University School of Medicine/Children's Healthcare of Atlanta
      • Contact: Jordyn Turner; Phone Number: 404-785-3690; Email: Jordyn.turner@choa.org
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ann and Robert H. Lurie Children's Hospital of Chicago
      • Contact: Catherine Chapin; Phone Number: 312-227-5511; Email: cchapin@luriechildrens.org
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
      • Contact: Ava Whalen; Email: w3876@cumc.columbia.edu
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
      • Contact: Puja Patel; Phone Number: 212-659-8039; Email: puja.patel4@mountsinai.org
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital
      • Contact: Jennifer Hawkins; Phone Number: 513-636-7818; Email: jennifer.hawkins@cchmc.org
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 15224
      • Children's Hospital of Philadelphia
      • Contact: Bryanna Domenick; Phone Number: 267-425-1078; Email: DOMENICKB@CHOP.edu
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Monroe Carell Jr. Children's Hospital at Vanderbilt
      • Contact: Carly Bhave; Email: carly.bhave@vumc.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Participant and parent or guardian must be able to understand and provide informed assent and consent, respectively
2. Recipient of a living or deceased donor Liver transplant (LTx) at <7 years of age
3. > 3 years but <7 years after LTx at the time of study enrollment
4. 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)
5. No Acute rejection (AR) or chronic rejection within 12 months of enrollment
6. 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)
7. Participants of childbearing potential must have a negative pregnancy test upon study entry

Exclusion Criteria:

1. Liver transplant (LTx) for autoimmune disease, including autoimmune hepatitis or primary sclerosing cholangitis
2. LTx for hepatitis B or hepatitis C
3. 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
4. >=50 percent dose increase in tacrolimus within 12 months of enrollment
5. Discontinued a second Immunosuppression (IS) agent within 12 months of enrollment
6. Systemic illness requiring chronic or recurrent use of IS for which there is a risk of reactivation if tacrolimus is reduced
7. Use of medication to treat systemic conditions which in the judgement of the investigator could influence results of the study
8. Active or chronic infection requiring treatment
9. Inability or unwillingness to comply with the study protocol
10. Use of investigational drug within 4 weeks (or 5 half-lives of investigational drug, whichever is longer) of enrollment
11. Has any condition that, in the opinion of the investigator, will interfere with safe participation in the trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: IS dose reduction; Eligible participants will reduce immunosuppression (IS) by 50 percent in two steps. For subjects taking tacrolimus once daily: reduce dose to 75 percent of initial dose for 6 weeks; reduce dose to 50 percent of initial dose For subjects taking tacrolimus twice daily: reduce evening such that the total daily dose is 75 percent of the initial dose for 6 weeks; 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; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Achieving successful 50 percent Immunosuppression (IS) reduction	Defined as meeting both biochemical and histological criteria of stability	At 18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical severity of Acute rejection (AR) episodes	Clinical severity - treatment required for resolution	At 18 months
Histological severity of Acute rejection (AR) episodes		At 18 months
The proportion of participants who experience Acute rejection (AR)	Defined as either biopsy-proven or clinical AR	At 18 months
Achieving clinically successful 50 percent Immunosuppression (IS) reduction	Defined as meeting biochemical but not histological criteria of stability	At 18 months

Other Outcome Measures

Outcome Measure	Time Frame
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
EXPLORATORY: The proportion of participants who develop de novo donor specific antibody (DSA)	At 18 months
EXPLORATORY: The association of intrapatient variability of tacrolimus blood levels and the outcome of 50 percent Immunosuppression (IS) dose reduction	At 18 months
EXPLORATORY: The association between tacrolimus exposure and the outcome of 50 percent Immunosuppression (IS) dose reduction	At 18 months
MECHANISTIC: The spatial metabolic landscape of liver biopsies and its relationship with clinical phenotypes	At 18 months
MECHANISTIC: The spatial metabolic landscape of liver biopsies and its relationship with cell phenotypes	At 18 months
MECHANISTIC: The spatial metabolic landscape of liver biopsies and its relationship with iSYNs	At 18 months
MECHANISTIC: Integration of image mass cytometry and state-of-the-art single-cell spatial transcriptomics to exhaustively map the immune microenvironment of liver allografts	At 18 months
MECHANISTIC: Pathway analysis of whole transcriptome data for iSYNs	At 18 months
MECHANISTIC: Nature of specific cell populations participating in iSYNs	At 18 months
MECHANISTIC: Density of aiSYNs in the baseline and in longitudinal biopsies	At 18 months

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Study Chair: 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

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Estimated): May 8, 2026
• Primary Completion (Estimated): April 1, 2031
• Study Completion (Estimated): October 1, 2031

Study Registration Dates

• First Submitted: April 16, 2026
• First Submitted That Met QC Criteria: April 16, 2026
• First Posted (Actual): April 24, 2026

Study Record Updates

• Last Update Posted (Actual): April 24, 2026
• Last Update Submitted That Met QC Criteria: April 16, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Immunosuppression; Liver transplant
• Other Study ID Numbers: DAIT RTB-018

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No