A 12-month, open-label, multicenter, randomized, safety, efficacy, pharmacokinetic (PK) and pharmacodynamic (PD) study of two regimens of anti-CD40 monoclonal antibody, CFZ533 vs. standard of care control, in adult de novo liver transplant recipients with a 12-month additional follow-up and a long-term extension (CONTRAIL I).
- Conditions
- Liver transplantation100196541005716710038430
- Registration Number
- NL-OMON55608
- Lead Sponsor
- ovartis
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 9
Screening period up to liver transplantation:
-Male or female subjects between 18 to 70 years of age.
-Recipients of a primary liver transplant from a deceased donor.
-Up to date vaccination as per local immunization schedules.
-Recipients tested negative for HIV.
-MELD score <=30 (based on laboratory values, using the United Network for Organ
Sharing (UNOS) MELD calculator: MELD calculator:
https://unos.org/resources/allocation-calculators/).
-Transplantation to occur within defined screening period following informed
consent signature.
At randomization:
-Recipients with no active HCV and HBV replication. Recipients with HCV
antibody positive should have no detectable HCV-RNA. Recipients with Hepatitis
B infection should have no detectable HBV DNA. Cases of spontaneous HCV
clearance should be discussed with sponsor.
-Allograft is functioning at an acceptable level by the time of randomization
as defined by AST, ALT, and Alkaline Phosphatase levels <= 5 times ULN and Total
Bilirubin <= 2 times ULN.
-Renal function (eGFR, MDRD-4 formula) >= 30 mL/min/1.73 m2 based on most recent
post-transplant value prior to randomization.
-Recipients who have been initiated on an immunosuppressive regimen that
contains TAC, mycophenolate mofetil (MMF) and corticosteroids (CS) as per
protocol.
Screening period up to liver transplantation:
-Recipients of multiple solid organ or islet cell transplants, or recipients
that have previously received a tissue transplant, or a combined liver-kidney
transplant.
-Recipients of a liver from a donor after cardiac death (DCD), from a living
donor, or of a split liver.
-Recipient who tests negative for Epstein Barr virus (EBV).
-Recipients receiving an ABO incompatible allograft.
-History of malignancy of any organ system (except hepatocellular carcinoma
(HCC) or localized basal cell carcinoma of the skin), treated or untreated,
within the past 5 years, regardless of whether there is evidence of local
recurrence or metastases.
-Hepatocellular carcinoma that does not fulfill Milan criteria (1 nodule <= 5
cm, 2-3 nodules all <= 3 cm, without evidence of metastatic disease or vascular
invasion) at the time of transplantation.
-Recipients transplanted for acute liver failure (does not apply to acute on
chronic liver failure).
-Any use of antibody induction therapy, or use of any immunosuppressive
medications (or other medications prohibited by the protocol)
-Patients who have received a live vaccine within four weeks prior to
transplantation.
-Recipients with donors positive for HIV.
-Recipients with donors positive for HBsAg.
-Recipients who are HCV antibody-positive without documented sustained viral
response (SVR) at 12 weeks after finishing anti HCV treatment (e.g.
direct-acting antivirals).
-Recipients with HCV RNA-positive donors.
At randomization:
-Any post-transplant history of thrombosis, occlusion or stent placement in any
hepatic arteries, hepatic veins, portal vein or inferior vena cava at any time
during the run-in period prior to randomization.
-Recipients with an absolute neutrophil count of < 1,000/mm³ or white blood
cell count of < 2,000/mm³.
-Recipients with clinically significant systemic infection requiring use of
intravenous (IV) antibiotics.
-Evidence of active tuberculosis (TB) infection (after anti-TB treatment,
patients with history of latent TB may become eligible according to national
guidelines).
-Recipients who are on renal replacement therapy at randomization.
-Any episode of acute rejection or suspected rejection prior to randomization.
-HCC participants whose explanted liver graft pathology report shows i) pTNM
stage beyond T2N0M0, ii) presence of mixed carcinoma, iii) microvascular
invasion despite pTNM stage.
-Participants with body weight < 30 kg or > 180 kg
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Evaluate the rate of composite efficacy failure (Biopsy Proven Acute Rejection<br /><br>(BPAR), graft loss (GL) or death) with CFZ533 600 mg and 300 mg regimens<br /><br>compared to tacrolimus (TAC) Control at Month 12 post-transplantation.</p><br>
- Secondary Outcome Measures
Name Time Method