EVR and EPO for Liver Transplant Tolerance
ConditionLiver Transplant
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorNational Institute of Allergy and Infectious Diseases (NIAID)
About this trial
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
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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)
Disqualifiers
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
Trial design
Design model
Single group
Treatments tested in this trial
Everolimus
DrugThe 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
DrugThe 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
Treatment groups
20 Participants
are divided into 1 treatment groupGroup A: Arm1Experimental treatment 2 interventions
Trial outcomes
Primary outcomes
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
Time frame
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
Time frame
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
Time frame
At 52 weeks post-immunosuppression withdrawal (ISW)Secondary outcomes
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.
Time frame
From baseline to 156 weeks post-ISW completion2
Severity of acute rejection
Time frame
From baseline to 156 weeks post-ISW completion3
Timing of acute rejection
Time frame
From baseline to 156 weeks post-ISW completion4
Incidence of chronic rejection
Time frame
From baseline to 156 weeks post-ISW completionSponsors and contacts
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Source ClinicalTrials.gov