Sustained Virological Response (SVR) to Antiviral Treatment of Liver Transplant Recipients With Recurrent Hepatitis C

NCT00938860 | Completed Phase 4 Results

• 2 other identifiers: COLO400A24302009-010806-12
• Study Type: interventional
• Target: 92
• Locations: 13 countries
• Sites: 45

Brief Summary

This study will assess the rates of Sustained Virological Response following anti-viral therapy with Peg-Interferon plus Ribavirin in patients that have been liver transplanted with recurrent Hepatitis C and treated with Neoral or tacrolimus.

Conditions

Hepatitis C; Liver Transplantation

Keywords

Hepatitis C; liver transplantation; anti-viral therapy

Outcome Measures

Primary Outcomes (1)

• Number of Participants Sustained Virological Response (SVR) Following Treatment of Hepatitis C Virus (HCV) Infection With Peg-IFN and Ribavirin in Liver Transplanted Recipients on Maintenance Therapy With Neoral or Tacrolimus

  The achievement of SVR, defined as HCV RNA below limit of detection at the end of AV treatment, 24 weeks after end of AV treatment (W24 post). A dichotomous variable (SVR achieved: Yes/No) was computed. A patient was classified as non-responder (SVR not achieved) if HCV RNA was detectable at the completion of antiviral treatment, at W24post, or at any time between W24 and completion of antiviral treatment. The HCV RNA detection limit was \<15 IU/ml (\<1.18 log IU/ml)

  Week 24

Secondary Outcomes (8)

• Number of Events of the Composite Endpoint of Biopsy Proven Acute Rejections (BPAR), Death or Graft Loss and of the Individual Components

  Week 80

• Number of Participants With Fibrosis Progression (Increase in Ishak-Knodell (IK) Score by at Least One Point From the Baseline)

  Week 80

• Number of Participants of Rapid Viral Response (RVR)

  Week 4

• Number of Participants of Early Viral Response (EVR)

  Week 12

• Number of Participants for the End of Treatment Response (ETR)

  Week 80

Study Arms (2)

Neoral

EXPERIMENTAL

Neoral capsules bid, Doses were to be adjusted as necessary to achieve and maintain recommended C0 (monitoring of trough levels) or C2 concentration 2 hours post dosing) target ranges

Drug: cyclosporin (Neoral)

tacrolimus

ACTIVE COMPARATOR

Tacrolimus capsules bid, doses were adjusted as necessary to achieve and maintain recommended C0 target ranges.

Drug: tacrolimus (Prograf)

Interventions

cyclosporin (Neoral) DRUG

Neoral capsules bid, Doses were to be adjusted as necessary to achieve and maintain recommended C0 (monitoring of trough levels) or C2 concentration 2 hours post dosing) target ranges

Neoral

tacrolimus (Prograf) DRUG

Tacrolimus capsules bid, doses were adjusted as necessary to achieve and maintain recommended C0 target ranges.

tacrolimus

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Liver transplantation performed at least 6 months and up to 5 years prior randomization and due to HCV cirrhosis, with or without pre-transplant hepatocellular carcinoma (HCC) within Milan or UCSF criteria
• Immunosuppresive regimen based on tacrolimus b.i.d.- (twice or once daily) for at least 6 months prior randomization
• Diagnosis of HCV genotypes 1 or 4 infection prior to transplantationconfirmed at screening
• Indication of treatment with Peg-IFN and ribavirin due to histological evidence of chronic HCV infection defined as a fibrosis stage equal or greater than 1 using the Ishak-Knodell scoring system (IK ≥1) in a liver biopsy performed at screening or up to 4 months prior to randomization.

You may not qualify if:

• Serum creatinine \>150 μmol/L (1.6 7 mg/dL) or eGFR \< 50 ml/min (4-variable Modification of Diet in Renal Disease \[MDRD Cockcroft-Gault formula\])
• Multi-organ transplant recipients
• Recent episode of steroid-treated acute rejection (AR) within 3 months prior to randomization, or \>1 episode of steroid-treated AR in the last 6 months, or any number of steroid-resistant AR episodes in the last 6 months including evidence of chronic rejection or ductopenia
• Evidence of conditions that could cause graft dysfunction other than HCV infection
• Patients with signs of decompensated liver disease, defined as presence of ascites, variceal bleeding, encephalopathy or deteriorated hepatic synthetic function (albumin \<3.5g/dL or, total direct bilirubin \>1.5mg/dL or, INR \>1.5)
• Co-infection with HIV or Hepatitis B (defined as HBsAg-positive) at screening
• Use of mTOR inhibitors (everolimus or sirolimus) in the 6 months prior to screening
• Antiviral treatment for HCV administered at any time after liver transplantation
• Patients on daily doses of corticosteroids higher than 5 mg/day
• Patients with fibrosing cholestatic hepatitis
• Patients with current diagnosis of malignancies, including lymphoproliferative disorders
• Patients with platelet count \<70,000/mm3 or neutrophiles \<1,500/mm3
• History of HCC outside Milan criteria based on radiology or UCSF criteria based on analysis of the explant

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (45)

Novartis Investigative Site

Phoenix, Arizona, 85054, United States

Location

Novartis Investigative Site

Palo Alto, California, 95128, United States

Location

Novartis Investigative Site

San Francisco, California, 94143-2205, United States

Location

Novartis Investigative Site

Gainesville, Florida, 32610, United States

Location

Novartis Investigative Site

Chapel Hill, North Carolina, 27599-7211, United States

Location

Novartis Investigative Site

Oklahoma City, Oklahoma, 73112, United States

Location

Novartis Investigative Site

Houston, Texas, 77030-2400, United States

Location

Novartis Investigative Site

Houston, Texas, 77030, United States

Location

Novartis Investigative Site

Madison, Wisconsin, 53792, United States

Location

Novartis Investigative Site

Brussels, 1070, Belgium

Location

Novartis Investigative Site

Fortaleza, Ceará, 60430-270, Brazil

Location

Novartis Investigative Site

São Paulo, São Paulo, 04023-900, Brazil

Location

Novartis Investigative Site

Edmonton, Alberta, T6G 2B7, Canada

Location

Novartis Investigative Site

Vancouver, British Columbia, V5Z 1M9, Canada

Location

Novartis Investigative Site

Winnipeg, Manitoba, R3E 0W3, Canada

Location

Novartis Investigative Site

London, Ontario, N6A 4G5, Canada

Location

Novartis Investigative Site

Toronto, Ontario, M5G 2C4, Canada

Location

Novartis Investigative Site

Bogotá, Cundinamarca, 110111, Colombia

Location

Novartis Investigative Site

Bogotá, Colombia

Location

Novartis Investigative Site

Créteil, 94000, France

Location

Novartis Investigative Site

Lyon, 69317, France

Location

Novartis Investigative Site

Montpellier, 34295, France

Location

Novartis Investigative Site

Paris, 75012, France

Location

Novartis Investigative Site

Toulouse, 31054, France

Location

Novartis Investigative Site

Villejuif, 94800, France

Location

Novartis Investigative Site

Mainz, Germany, 55131, Germany

Location

Novartis Investigative Site

Frankfurt, 60590, Germany

Location

Novartis Investigative Site

Hamburg, 20246, Germany

Location

Novartis Investigative Site

München, 81377, Germany

Location

Novartis Investigative Site

Bologna, BO, 40138, Italy

Location

Novartis Investigative Site

Padua, PD, 35128, Italy

Location

Novartis Investigative Site

Udine, UD, 33100, Italy

Location

Novartis Investigative Site

Moscow, 123182, Russia

Location

Novartis Investigative Site

Moscow, 129010, Russia

Location

Novartis Investigative Site

Seoul, Korea, 110 744, South Korea

Location

Novartis Investigative Site

Seoul, Korea, 120-752, South Korea

Location

Novartis Investigative Site

Seoul, Korea, 135-710, South Korea

Location

Novartis Investigative Site

Seoul, Korea, 137-701, South Korea

Location

Novartis Investigative Site

Valladolid, Castille and León, 47012, Spain

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

Barcelona, Catalonia, 08036, Spain

Location

Novartis Investigative Site

Santiago de Compostela, Galicia, 15706, Spain

Location

Novartis Investigative Site

Oviedo, Principality of Asturias, 33006, Spain

Location

Novartis Investigative Site

Zurich, Switzerland, 8091, Switzerland

Location

Novartis Investigative Site

Birmingham, B15 2TT, United Kingdom

Location

MeSH Terms

Conditions

Hepatitis C

Interventions

Cyclosporine; Tacrolimus

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

trialandresults.registries@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 13, 2009
• First Posted: July 14, 2009
• Study Start: September 1, 2009
• Primary Completion: May 1, 2013
• Study Completion: May 1, 2013
• Last Updated: May 22, 2015
• Results First Posted: May 26, 2014

Record last verified: 2015-05

Locations

GB (1); BR (2); US (9); DE (4); CA (5); BE (1); FR (6); CO (2); RU (2); IT (3); KR (4); ES (5); CH (1)