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

Condition(s) targeted: Recurrent Hepatitis C

Intervention: CsA-TAC (standard Treatment) (Drug); Everolimus (Drug)

Phase: Phase 2

Status: Terminated

Sponsored by: Novartis Pharmaceuticals

Official(s) and/or principal investigator(s):
Novartis Pharmaceuticals, Study Director, Affiliation: Novartis Pharmaceuticals

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

Official title: A Randomized, Controlled, Open Label, Two Arms, Exploratory Study to Evaluate the Effect of Everolimus on Histologically Assessed Fibrosis Progression (Ishak-Knodell) in Liver Transplant Recipients With Recurrent Hepatitis C Viral Infection as Compared to Standard Treatment.

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

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

Secondary outcome:

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

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

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

Comparison of the Effect of Both Regimens in the Necroinflammatory Grading Score (Ishak-Knodell) (Portal Inflammation)

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

Percentage of Patients in Each Study Arm With Increase of ≥1 Point in the Ishak-Knodell Staging Score in Fibrosis

Change From Baseline in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Viral Load at 12 and 24 Months Post Randomization

Minimum age: 18 Years. Maximum age: 65 Years. Gender(s): Both.

Criteria:

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.

Novartis Investigative site, Buenos Aires, Argentina

Starting date: December 2007
Last updated: August 2, 2012