EVR and EPO for Liver Transplant Tolerance

NCT06832189 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: DAIT ITN101ST
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 3

Brief 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. 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

Conditions

Liver Transplant

Keywords

Everolimus; Liver Transplant; Epoetin alfa; Tacrolimus

Outcome Measures

Primary Outcomes (3)

• 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

  At 52 weeks post-immunosuppression withdrawal (ISW)

• 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

  At 52 weeks post-immunosuppression withdrawal (ISW)

• 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

  At 52 weeks post-immunosuppression withdrawal (ISW)

Secondary Outcomes (20)

• Incidence of acute rejection

  From baseline to 156 weeks post-ISW completion

• Severity of acute rejection

  From baseline to 156 weeks post-ISW completion

• Timing of acute rejection

  From baseline to 156 weeks post-ISW completion

• Incidence of chronic rejection

  From baseline to 156 weeks post-ISW completion

• Severity of chronic rejection

  From baseline to 156 weeks post-ISW completion

Study Arms (1)

Arm1

EXPERIMENTAL

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.

Drug: Everolimus; Drug: Epoetin alfa

Interventions

Everolimus 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.

Arm1

Epoetin alfa 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

Also known as: EPO, Erythropoietin, Procrit

Arm1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject must be able to understand and provide informed consent
• 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
• 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

You may not qualify if:

• Inability of a subject to comply with study protocol
• 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
• 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)

Sponsors & Collaborators

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

Study Sites (3)

University of California San Francisco School of Medicine

San Francisco, California, 94143, United States

RECRUITING

Northwestern University Feinberg School of Medicine

Chicago, Illinois, 60611, United States

RECRUITING

University of Pennsylvania Medical Center

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Related Links

• Immune Tolerance Network (ITN)
• National Institute of Allergy and Infectious Diseases (NIAID)
• Division of Allergy, Immunology, and Transplantation (DAIT)

MeSH Terms

Interventions

Everolimus; Epoetin Alfa; Erythropoietin

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Sandy Feng, MD, PhD

  University of California, San Francisco

  STUDY CHAIR

• Paolo Cravedi, M.D., Ph.D.

  Icahn School of Medicine at Mount Sinai: Transplantation

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 12, 2025
• First Posted: February 18, 2025
• Study Start: January 21, 2026
• Primary Completion (Estimated): June 1, 2030
• Study Completion (Estimated): June 1, 2030
• Last Updated: January 28, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Time Frame: On average, within 24 months after database lock for the trial.
• Access Criteria: Open access.

Locations

US (3)