EVR and EPO for Liver Transplant Tolerance

NCT ID: NCT06832189

Last Updated: 2026-01-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-12-31

Study Completion Date

2030-06-01

Brief Summary

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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

Detailed Description

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Conditions

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Liver Transplant

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm1

Adult 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.

Group Type EXPERIMENTAL

Everolimus

Intervention Type DRUG

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 alfa

Intervention Type DRUG

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

Interventions

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Everolimus

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.

Intervention Type DRUG

Epoetin alfa

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

Intervention Type DRUG

Other Intervention Names

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EPO Erythropoietin Procrit

Eligibility Criteria

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Inclusion Criteria

1. Subject must be able to understand and provide informed consent
2. 1-10 years post-liver transplant
3. 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.
4. Gamma glutamyl transferase (GGT) and alanine transaminase (ALT) \<= upper limit of normal (ULN)
5. Estimated glomerular filtration rate (GFR) \>=40 mL/min/1.73 m\^2 using the CKD-EPI 2021 equation
6. Female subjects of reproductive potential must have a negative pregnancy test upon study entry
7. 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
8. 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
9. 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)
10. 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)
11. 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
12. 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

Exclusion Criteria

1. Inability of a subject to comply with study protocol
2. Any medical condition requiring chronic systemic corticosteroid, e.g., severe reactive airways disease. Use of inhaled steroids is not an exclusion
3. Autoimmune cause of liver disease (including autoimmune hepatitis (AIH), primary sclerosing cholangitis, primary biliary cirrhosis)
4. Diagnosis of rejection within 52 weeks prior to screening
5. Donor human leukocyte antigen (HLA) typing unavailable or inadequate for assigning donor-specific antibody (DSA)
6. Need for uninterrupted anticoagulation
7. Known active current or history of invasive fungal infection, or mycobacterial infection within 1 year prior to screening
8. Human immunodeficiency virus (HIV)-positive
9. Serious uncontrolled concomitant major organ disease
10. Recipient of non-liver solid organ or bone marrow transplant
11. Any infection requiring hospitalization and IV antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks
12. 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

1. the last alpha fetoprotein obtained within 3 months prior to liver transplantation was \< 400 microg/L, and
2. 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
13. Neutropenia (absolute neutrophil count or ANC \<1000 microliter) within 4 weeks prior to study enrollment
14. History of hypersensitivity to Epoetin (EPO) or mammalian Target of Rapamycin inhibitor (mTOR-I)
15. History of angioedema
16. History of hereditary disorders of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption. History of lactose intolerance is not an exclusion
17. 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
18. History of venous or arterial thrombosis or thromboembolism, acute MI, or thrombotic stroke
19. History of Budd Chiari syndrome
20. Hemoglobin \> 13.5 g/dl
21. Plasma fibrinogen or D-dimer level \> ULN
22. Planned major surgery within the next 12 months
23. Uncontrolled severe hypertension
24. Uncontrolled clinically significant cardiac arrhythmia
25. Proteinuria with urine protein/creatinine \>0.5 g/g
26. Severe hyperlipidemia with total cholesterol \>350 mg/dl or triglycerides \>1000 mg/dl
27. Current alcohol, drug, or chemical dependency
28. Currently pregnant or nursing
29. Current treatment with an estrogen-containing oral contraceptive, or systemic estrogen replacement therapy
30. Treatment with an immunomodulatory biological drug within 12 weeks of study entry
31. Immunization with live vaccine within 2 weeks of study baseline visit
32. Treatment with any investigational agent within 4 weeks (or 5 half-lives of investigational drug, whichever is longer) of screening
33. 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Sandy Feng, MD, PhD

Role: STUDY_CHAIR

University of California, San Francisco

Paolo Cravedi, M.D., Ph.D.

Role: STUDY_CHAIR

Icahn School of Medicine at Mount Sinai: Transplantation

Locations

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University of California San Francisco School of Medicine

San Francisco, California, United States

Site Status RECRUITING

Northwestern University Feinberg School of Medicine

Chicago, Illinois, United States

Site Status RECRUITING

University of Pennsylvania Medical Center

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

Countries

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United States

Facility Contacts

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Joanne Kwan, BS

Role: primary

415-476-2574

Laura Adams, RN

Role: primary

312-694-0242

Mary Kaminski, PA

Role: primary

215-847-8750

Related Links

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https://www.immunetolerance.org/

Immune Tolerance Network (ITN)

https://www.niaid.nih.gov/

National Institute of Allergy and Infectious Diseases (NIAID)

https://www.niaid.nih.gov/about/dait

Division of Allergy, Immunology, and Transplantation (DAIT)

Other Identifiers

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DAIT ITN101ST

Identifier Type: -

Identifier Source: org_study_id

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