Efficacy of Everolimus as Inhibitor of Fibrosis Progression in Liver Transplant Patients With Recurrence of Hepatitis C Viral Infection

Phase 2TerminatedNCT00582738

Novartis Pharmaceuticals43 enrolled

Overview

This study will assess the efficacy of everolimus as an inhibitor of fibrosis progression in liver transplant patients who have a recurrence of hepatitis C viral infection in the transplant

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Recurrent Hepatitis C

Interventions

CsA-TAC (standard Treatment)DRUG

Continuation of current immunosuppressive regimen (continuation of CNI with or without MPA, with or without steroids) / no everolimus introduction.

EverolimusDRUG

Hepatitis C recurrence after orthotopic liver transplantation (OLT)

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Male or female patients 18 - 65 years of age * Recipients of deceased or living donors * Patients who had undergone primary liver transplantation at least 6 months before enrolment * Recurrent Hepatitis C viral infection and histologically confirmed liver fibrosis (stage I-IV in the Ishak-Knodell scale) obtained at baseline or within the previous 6 months to the date of enrolment * Patients receiving tacrolimus or cyclosporine micro-emulsion with or without - Mycophenolic acid (MPA), with or without steroids. * Absence of acute rejection episodes within the previous 6 months to the date of enrolment * Patient in whom an allograft biopsy will not be contraindicated * Patient willing and capable of giving written informed consent for study participation and able to participate in the study for 24 months * Patients with Hepatocellular carcinoma (HCC) within the University California, San Francisco (UCSF) Criteria and no recurrence for at least 18 months after OLT. Exclusion Criteria: * Recipients of multiple organ transplants or patients who have undergone retransplantation * Current biliary complications * History of drug or alcohol abuse within 1 year before enrolment * Patients treated with anti-hepatitis C virus treatment at the time of enrollment or within the previous month to the date of enrolment * Co-infection with Hepatitis B virus (HBV) or Human Immunodeficiency Virus (HIV) * Patients with Leukocyte count (WBC) \< 3000/mm3, platelet count \< 75000/mm3 or Hemoglobin (Hb) \< 8 g/dl * Patients with proteinuria \>1g/24 hours * Patient with a current severe systemic infection Other protocol defined inclusion/exclusion criteria may apply.

Locations (1)

Novartis Investigative site

Buenos Aires, Argentina

Outcomes

Primary Outcomes

Change From Baseline in Fibrosis Staging Score (Measured by the Ishak-Knodell Staging Score) Between Baseline and 24 Months Post-transplant.

Ishak-Knodell Score: 0=No fibrosis; 01=Fibrous expansion of some portal areas, with or without short fibrous septa; 02=Fibrous expansion of most portal areas, with or without short fibrous septa; 03=Fibrous expansion of most portal areas, with occasional portal to portal (P-P) bridging; 04=Fibrous expansion of portal areas, with marked bridging (portal to portal (P-P) as well as portal to central (P-C)); 05=Marked bridging (P-P and/or P-C) with occasional nodules (incomplete cirrhosis); 06=Cirrhosis, probable or definite Decrease in score from baseline indicates improvement

Time frame: baseline, 24 Months

Secondary Outcomes

Change From Baseline in Fibrosis Metavir Scoring at 12 and 24 Months Post Randomization

Metavir Score: F0=No fibrosis; F1=Portal fibrosis without septa; F2=Portal fibrosis with rare septa; F3=Numerous septa without cirrhosis Decrease in score from baseline indicates improvement

Time frame: Baseline, 12 months, 24 months

Percentage of Patients With Death, Graft Loss and Biopsy Proven Acute Rejection (BPAR) Between Study Groups

Time frame: 24 Months

Number of Patients With Events (Progression to Cirrhosis, Retransplantation, HCV Related Death, First BPAR, Graft Loss)at 12 and 24 Months

Time frame: 12 months, 24 months

Comparison of Renal Function (Glomerular Filtration Rate [GFR] Calculated Using the Modification of Diet in Renal Disease Study Group [MDRD] Formula) Between Study Groups

GFR Month 9 value if available, otherwise minimal first year post-randomization available value. Imputation rule of missing Month 24 GFR values: GFR Month 18 value if available, otherwise Month 12 GFR is used. Least square means are from an ANCOVA model containing treatment as factor and baseline eGFR as a covariate.

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Comparison of the Effect of Both Regimens on the Inflammatory (Acti-test) and Fibrosis (Fibro-test) Components of Fibrosure, and on Fibrosis Area Assessed by Histomorphometry

The Fibrosure test is the combination of Fibro-test + Acti-test. FibroTest (FT) was for the assessment of fibrosis. Fibro test was calculated using an original combination of five highly concentrated serum biochemical markers; alpha2macroglobulin, haptoglobin, apolipoprotein A1, total bilirubin and gammaglutamyltransferase (GGT). FibroTest scores range from 0.00 to 1.00 where 0.0-0.21 is no fibrosis and \>= 0.59 is cirrhosis. Acti-test was calculated using 6 serum biochemical markers; alpha2macroglobulin, haptoglobin, apolipoprotein A1, total bilirubin, GGT and alanine aminotransferase (ALT). ActiTest (AT) was used for the assessment of necroinflammatory activity. Test score ranges from 0.00 to 1.00, where 0.00-0.17 indicates no necrosis and \>= 0.61 indicates severe necrosis If 12-month Actitest value was the last available assessment, the value is used to impute the final staging score(End of Study)

Time frame: baseline, 12 and 24 months