Actively Recruiting

Phase 1
Age: 18Years +
All Genders
ID06832189

Everolimus and Epoetin for Sustained Liver Transplant Tolerance (EVEREST)(ITN101ST)

Led by National Institute of Allergy and Infectious Diseases (NIAID) · Updated on 2026-04-06

20

Participants Needed

3

Research Sites

N/A

Total Duration

On this page

AI-Summary

What this Trial Is About

Researchers are evaluating the safety of using Everolimus (EVR) and epoetin alfa (EPO) to induce operational tolerance in stable adult liver transplant recipients who are currently on tacrolimus (TAC)-based immunosuppression. This open-label, single-arm, multicenter phase 1b study focuses on adults 1 to 10 years after liver transplant. The goal is to assess if switching from TAC to EVR combined with EPO can safely allow phased withdrawal from immunosuppression. Participants will transition from TAC to EVR with dosing adjusted based on their prior TAC dose to maintain specific blood levels of EVR. They will receive five doses of EPO injected under the skin every eight weeks at weeks 16, 24, 32, 40, and 48. As EVR is started, participants will begin a gradual withdrawal from EVR itself under careful monitoring. Up to 20 participants will be enrolled in this study. During the study, researchers will monitor participants for infections, malignancies, serious adverse events, and signs of rejection over a period extending up to 156 weeks after immunosuppression withdrawal. They will assess kidney function, antibody development, graft loss, and overall clinical stability off immunosuppression. Safety and effectiveness of the treatment regimen will be closely followed through laboratory tests, clinical assessments, and medication adjustments throughout the trial period.

CONDITIONS

Brief Title

EVR and EPO for Liver Transplant Tolerance

Who Can Participate

Age: 18Years +
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Able to understand and provide informed consent
  • Liver transplant occurred 1 to 10 years prior
  • On tacrolimus-based maintenance immunosuppression without corticosteroids
  • If on mycophenolate mofetil or mycophenolic acid, doses must be at or below specified limits
  • Tacrolimus levels below 8 ng/ml on two recent tests within 3 months
  • Gamma glutamyl transferase (GGT) and alanine transaminase (ALT) within normal limits
  • Estimated glomerular filtration rate (GFR) of 40 mL/min/1.73 m2 or higher
  • Female participants of reproductive potential must have a negative pregnancy test and agree to use FDA-approved birth control
  • Up-to-date vaccinations or documented immunity as per transplant vaccine guidelines
  • Negative tuberculosis test or completed appropriate latent tuberculosis treatment
  • Negative HIV test within past 12 months
  • Negative hepatitis C antibody test or documented negative RNA tests if history of hepatitis C
  • Negative hepatitis B surface antigen and core antibody or on antiviral therapy with negative HBV DNA test
Not Eligible

You will not qualify if you...

  • Unable to comply with study protocol
  • Need for chronic systemic corticosteroids
  • Autoimmune liver disease
  • Rejection diagnosis within 52 weeks before screening
  • Donor HLA typing unavailable or inadequate
  • Need for continuous anticoagulation
  • Active or recent invasive fungal or mycobacterial infection
  • HIV-positive
  • Serious uncontrolled major organ disease
  • Recipient of other solid organ or bone marrow transplant
  • Recent infection requiring hospitalization or antibiotics
  • Malignancy within last 5 years except certain treated skin or cervical cancers
  • Neutropenia within 4 weeks before enrollment
  • Allergic reaction history to Epoetin or mTOR inhibitors
  • History of angioedema
  • Certain hereditary disorders related to sugar metabolism
  • Genetic disorders increasing blood clot risk
  • History of thrombosis or thromboembolism except isolated portal vein thrombosis
  • History of Budd Chiari syndrome
  • Hemoglobin above 13.5 g/dl
  • Elevated fibrinogen or D-dimer levels
  • Planned major surgery within 12 months
  • Uncontrolled severe hypertension or significant cardiac arrhythmia
  • Proteinuria above specified level
  • Severe hyperlipidemia
  • Current substance dependency
  • Pregnant or breastfeeding
  • Use of estrogen-containing contraceptives or systemic estrogen therapy
  • Recent treatment with immunomodulatory biologic drugs
  • Recent live vaccine immunization
  • Recent investigational drug treatment
  • Other medical conditions posing risks or interfering with study participation as judged by investigator

AI-Screening

AI-Powered Screening

Complete this quick 3-step screening to check your eligibility

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Your Study Journey

Screening

Duration - 2 to 4 weeks

Participants are screened for eligibility to participate in the trial.

1 visit (in-person)

Treatment

Duration - Approximately 48 weeks for epoetin alfa dosing; phased withdrawal duration varies

Participants transition from Tacrolimus to Everolimus, receive five doses of epoetin alfa, and undergo phased withdrawal from Everolimus as part of the treatment regimen for liver transplant tolerance.

5 visits for epoetin alfa dosing every 8 weeks

Follow-up

Duration - Up to 156 weeks post-immunosuppression withdrawal

Participants are monitored for safety, rejection, and transplant tolerance outcomes after completion of immunosuppression withdrawal.

Regular monitoring visits during follow-up period

Trial Site Locations

Total: 3 locations

1

University of California San Francisco School of Medicine

San Francisco, California, United States, 94143

Actively Recruiting

2

Northwestern University Feinberg School of Medicine

Chicago, Illinois, United States, 60611

Actively Recruiting

3

University of Pennsylvania Medical Center

Philadelphia, Pennsylvania, United States, 19104

Actively Recruiting

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How is the study designed?

Study Type

INTERVENTIONAL

Masking

NONE

Allocation

NA

Model

SINGLE_GROUP

Primary Purpose

TREATMENT

Number of Arms

1

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