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Liver TransplantPhase 1EVERESTNCT06832189

EVR and EPO for Liver Transplant Tolerance

A Phase 1 study testing Everolimus and Epoetin alfa in people with Liver Transplant, run by National Institute of Allergy and Infectious Diseases (NIAID) at 3 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

This is an open label, single-arm, multicenter phase 1b study of stable adult liver transplant recipients on a tacrolimus (TAC)-based immunosuppression (IS) regimen who will transition from TAC to Everolimus (EVR), receive five doses of EPO and concurrently initiate phased withdrawal from EVR. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Liver Transplant
What is being tested?
Everolimus and Epoetin alfa
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
3 sitesUnited States
Study dates
21 Jan 2026to 1 Jun 2030
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Subject must be able to understand and provide informed consent
  • 1-10 years post-liver transplant
  • Tacrolimus-containing maintenance immunosuppression (IS) regimen without corticosteroid. Mycophenolate mofetil (MMF) dose must be <=2000 mg daily or mycophenolic acid (MPA) dose<=1440 mg daily (if on MMF or MPA). Tacrolimus level must be <8 ng/ml on the 2 most recent laboratory results within 3 months.
  • Gamma glutamyl transferase (GGT) and alanine transaminase (ALT) <= upper limit of normal (ULN)
  • Estimated glomerular filtration rate (GFR) >=40 mL/min/1.73 m^2 using the CKD-EPI 2021 equation
  • Female subjects of reproductive potential must have a negative pregnancy test upon study entry
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  • Female subjects with reproductive potential, must agree to use Food and Drug Administration (FDA)-approved methods of birth control for the duration of the study
  • Subjects must have current vaccinations or documented immunity as per the Division of Allergy, Immunology, and Transplantation (DAIT) vaccine guidance for subjects in transplant trials
  • Negative result of most recent tuberculosis (TB) testing or appropriately completed latent tuberculosis infection (LTBI) therapy. Testing should be conducted using either a purified protein derivative (PPD) or interferon-gamma release assay (i.e., QuantiFERON-TB, T-SPOT.TB). Results from tests performed within 12 months prior to study entry are acceptable in the absence of any intervening exposure to TB. Subjects with a positive test for LTBI must complete appropriate therapy for LTBI. LTBI treatment regimens should be among those endorsed by the Centers for Disease Control and Prevention (CDC)
  • Negative FDA-approved test for human immunodeficiency virus (HIV) diagnosis at screening or as documented in medical record, up to 12 months prior to screening)
  • Negative hepatitis C antibody test at screening or as documented in medical record, up to 12 months prior to screening, in subjects without a history of hepatitis C. If there is a history of treated hepatitis C, then documentation of two consecutive negative hepatitis C virus (HCV) quantitative RNA polymerase chain reaction (PCR) tests separated by at least 3 months is required. Untreated subjects with positive HCV antibody and a single negative quantitative HCV RNA are eligible. Historical negative HCV RNA results are acceptable in the above two cases with positive HCV antibody
  • Negative hepatitis B surface antigen and negative hepatitis B core antibody in subjects without a history of hepatitis B virus (HBV) infection, up to 12 months prior to screening. Those with known hepatitis B infection or positive hepatitis B surface antigen or positive hepatitis B core antibody must be on antiviral therapy and have negative HBV DNA quantitative PCR at screening

Who cannot join

  • Inability of a subject to comply with study protocol
  • Any medical condition requiring chronic systemic corticosteroid, e.g., severe reactive airways disease. Use of inhaled steroids is not an exclusion
  • Autoimmune cause of liver disease (including autoimmune hepatitis (AIH), primary sclerosing cholangitis, primary biliary cirrhosis)
  • Diagnosis of rejection within 52 weeks prior to screening
  • Donor human leukocyte antigen (HLA) typing unavailable or inadequate for assigning donor-specific antibody (DSA)
  • Need for uninterrupted anticoagulation
Show all 35Show fewer
  • Known active current or history of invasive fungal infection, or mycobacterial infection within 1 year prior to screening
  • Human immunodeficiency virus (HIV)-positive
  • Serious uncontrolled concomitant major organ disease
  • Recipient of non-liver solid organ or bone marrow transplant
  • Any infection requiring hospitalization and IV antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks
  • Malignancy within the last 5 years except treated basal and squamous cell cancer of the skin or treated in situ cervical cancer. History of hepatocellular carcinoma in the explanted liver is acceptable provided that
  • the last alpha fetoprotein obtained within 3 months prior to liver transplantation was < 400 microg/L, and
  • the recipients' explanted liver did not have evidence of increased risk of recurrent cancer, i.e., explant was within the Milan criteria, with no vascular invasion, and with no cholangiocarcinoma morphology
  • Neutropenia (absolute neutrophil count or ANC <1000 microliter) within 4 weeks prior to study enrollment
  • History of hypersensitivity to Epoetin (EPO) or mammalian Target of Rapamycin inhibitor (mTOR-I)
  • History of angioedema
  • History of hereditary disorders of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption. History of lactose intolerance is not an exclusion
  • History of genetic disorders predisposing to thrombosis including but not limited to Factor V Leiden mutation, prothrombin 20210, protein C deficiency, protein S deficiency, antithrombin III deficiency
  • History of venous or arterial thrombosis or thromboembolism, acute MI, or thrombotic stroke except for a history of isolated portal vein thrombosis in the setting of hepatic cirrhosis
  • History of Budd Chiari syndrome
  • Hemoglobin > 13.5 g/dl
  • Plasma fibrinogen or D-dimer level > ULN
  • Planned major surgery within the next 12 months
  • Uncontrolled severe hypertension
  • Uncontrolled clinically significant cardiac arrhythmia
  • Proteinuria with urine protein/creatinine >0.5 g/g
  • Severe hyperlipidemia with total cholesterol >350 mg/dl or triglycerides >1000 mg/dl
  • Current alcohol, drug, or chemical dependency
  • Currently pregnant or nursing
  • Current treatment with an estrogen-containing oral contraceptive, or systemic estrogen replacement therapy
  • Treatment with an immunomodulatory biological drug within 12 weeks of study entry
  • Immunization with live vaccine within 2 weeks of study baseline visit
  • Treatment with any investigational agent within 4 weeks (or 5 half-lives of investigational drug, whichever is longer) of screening
  • Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the subject's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study

Trial locations and contacts

3 sites in 1 country. Contact the study team or a site near you to ask about taking part.

United States3 sites, 3 recruiting

  • Northwestern University Feinberg School of Medicine

    Chicago, Illinois, 60611

    Laura Adams, RN, 312-694-0242, Laura.adams@nm.org

    Recruiting

  • University of Pennsylvania Medical Center

    Philadelphia, Pennsylvania, 19104

    Mary Kaminski, PA, 215-847-8750, Mary.kaminski@pennmedicine.upenn.edu

    Recruiting

  • University of California San Francisco School of Medicine

    San Francisco, California, 94143

    Joanne Kwan, BS, 415-476-2574, Joanne.kwan@ucsf.edu

    Recruiting

Other trials in United States

About this study

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

This is an open label, single-arm, multicenter phase 1b study of stable adult liver transplant recipients on a tacrolimus (TAC)-based immunosuppression (IS) regimen who will transition from TAC to Everolimus (EVR), receive five doses of EPO and concurrently initiate phased withdrawal from EVR.

The primary objective is to test the safety of administering Everolimus (EVR) and epoetin alfa (EPO) to induce operational tolerance in stable adult liver transplant recipients

Being tested
Everolimus, Epoetin alfa
Keywords
Everolimus, Liver Transplant, Epoetin alfa, Tacrolimus

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EverolimusDrug

    The starting dose of EVR will be based on the maintenance TAC dose of the subject at study entry:

    1. EVR 1 mg PO BID if TAC dose is <=2 mg BID
    2. EVR 2 mg PO BID if TAC dose is 2.5-7 mg BID
    3. EVR 3 mg PO BID if TAC dose is >7 mg BID

    The dosage will be adjusted as needed to achieve and maintain EVR trough concentration of 5-8 ng/mL.

  • Epoetin alfaDrug

    Also called EPO, Erythropoietin, Procrit

    The dose used in this study is 10,000 units SC every 8 weeks (at study weeks 16, 24, 32, 40 and 48) for five doses

Study groups in NCT06832189
Study groupRoleWhat they receive
Arm1ExperimentalAdult liver transplant recipients on a TAC-based IS regimen will transition from Tacrolimus (TAC) to Everolimus (EVR), receive five doses of epoetin alfa (EPO) and concurrently initiate phased withdrawal from EVR. Target accrual for the study is 20 subjects who receive any dose of EPO, and up to 20 donors.
Receives: Drug: Everolimus; Drug: Epoetin alfa

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The proportion of subjects free of opportunistic infection attributed to the investigational study regimen

    The primary analysis will be performed using the Intention-to-Treat (ITT) and Per-Protocol (PP) analysis populations, and the proportion will be summarized with a point estimate and a two-sided, 95% confidence interval (CI) calculated using the Clopper-Pearson (exact) method

    Measured: At 52 weeks post-immunosuppression withdrawal (ISW)

  2. The proportion of subjects free of malignancy attributed to the investigational study regimen

    The primary analysis will be performed using the Intention-to-Treat (ITT) and Per-Protocol (PP) analysis populations, and the proportion will be summarized with a point estimate and a two-sided, 95% confidence interval (CI) calculated using the Clopper-Pearson (exact) method

    Measured: At 52 weeks post-immunosuppression withdrawal (ISW)

  3. The proportion of subjects free of serious adverse events (SAEs) attributed to the investigational study regimen

    The primary analysis will be performed using the Intention-to-Treat (ITT) and Per-Protocol (PP) analysis populations, and the proportion will be summarized with a point estimate and a two-sided, 95% confidence interval (CI) calculated using the Clopper-Pearson (exact) method

    Measured: At 52 weeks post-immunosuppression withdrawal (ISW)

Secondary outcomes (20)

  1. Incidence of acute rejection

    All secondary endpoints (except for the change in eGFR) consider incidences or proportions, and therefore will follow the same analysis approach as the primary safety endpoint. Analysis will be performed using the Intention-to-Treat (ITT) and Per-Protocol (PP) analysis populations

    The proportion will be summarized with a point estimate and a two-sided, 95% confidence interval (CI) calculated using the Clopper-Pearson (exact) method.

    Measured: From baseline to 156 weeks post-ISW completion

  2. Severity of acute rejection

    Measured: From baseline to 156 weeks post-ISW completion

  3. Timing of acute rejection

    Measured: From baseline to 156 weeks post-ISW completion

  4. Incidence of chronic rejection

    Measured: From baseline to 156 weeks post-ISW completion

  5. Severity of chronic rejection

    Measured: From baseline to 156 weeks post-ISW completion

  6. Timing of chronic rejection

    Measured: From baseline to 156 weeks post-ISW completion

  7. Incidence of de novo class II donor specific antibody (DSA)

    Measured: From baseline to 156 weeks post-ISW completion

  8. Incidence of graft loss

    Measured: From baseline to 156 weeks post-ISW completion

  9. Incidence of all-cause mortality

    Measured: From baseline to 156 weeks post-ISW completion

  10. Incidence of study-related Serious Adverse Event (SAE)s

    Measured: From baseline to 156 weeks post-ISW completion

  11. Incidence of opportunistic infections

    Measured: From baseline to 156 weeks post-ISW completion

  12. Incidence of malignancy

    Measured: From baseline to 156 weeks post-ISW completion

  13. Incidence of Everolimus (EVR) discontinuation due to Adverse Events (AEs)

    Measured: From baseline to 156 weeks post-ISW completion

  14. Incidence of polycythemia in the study

    Measured: From baseline to 156 weeks post-ISW completion

  15. Incidence of thromboembolism in the study

    Measured: From baseline to 156 weeks post-ISW completion

  16. Proportion of subjects with operational tolerance as defined by no rejection

    (clinical or biopsy-proven) since enrollment in the study and a liver biopsy demonstrating histologic stability and absence of rejection per the criteria delineated by the Banff Working Group on Liver Allograft Pathology [1], as assessed by the central pathology laboratory.

    Measured: At 52 weeks after completion of immunosuppression withdrawal (ISW)

  17. Change in estimated glomerular filtration rate (eGFR)

    Change in eGFR will be summarized using descriptive statistics (i.e., number of participants (n), mean, standard deviation (SD), median, first quartile (Q1), third quartile(Q3), minimum and maximum) at baseline, follow-up and for the change score. Follow-up scores will not be imputed. The ITT and PP analysis populations will be used.

    Measured: From baseline to 156 weeks after completion or failure of ISW

  18. Proportion of subjects with operational tolerance

    Measured: At 156 weeks after completion of immunosuppression withdrawal (ISW)

  19. Proportion of subjects who are clinically stable off immunosuppression (IS)

    Measured: At 52 weeks after completion of immunosuppression withdrawal (ISW)

  20. Proportion of subjects who are clinically stable off immunosuppression (IS)

    Measured: At 156 weeks after completion of immunosuppression withdrawal (ISW)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Feb 2025
  2. Study start21 Jan 2026
  3. Primary completion1 Jun 2030 (estimated)
  4. Study completion1 Jun 2030 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
20 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06832189
Sponsor's protocol ID
DAIT ITN101ST
Acronym
EVEREST
Status last verified
Apr 2026
First submitted
12 Feb 2025
Last updated
6 Apr 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: The plan is to share data upon completion of the study in: Immunology Database and Analysis Portal (ImmPort), a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Everolimus and Epoetin alfa in people with Liver Transplant, run by National Institute of Allergy and Infectious Diseases (NIAID) at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 35 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 6 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The proportion of subjects free of opportunistic infection attributed to the investigational study regimen (time frame: At 52 weeks post-immunosuppression withdrawal (ISW)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06832189.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Apr 2026.

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