An Efficacy and Safety Study of Telaprevir in Patients With Genotype 1 Hepatitis C Infection After Liver Transplantation

Chronic Hepatitis C Virus (HCV) Infection Clinical Trial

— REPLACE  

Official title:

Open-Label, Phase 3b Study To Determine Efficacy and Safety of Telaprevir, Pegylated-Interferon-alfa-2a and Ribavirin in Hepatitis C Genotype 1 Infected, Stable Liver Transplant Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01571583
• Other study ID #: CR018721
• Secondary ID: VX-950HPC3006201
• Status: Completed
• Phase: Phase 3
• First received: December 16, 2011
• Last updated: June 29, 2016
• Start date: February 2012
• Est. completion date: July 2014

Study information

• Verified date: June 2016
• Source: Janssen-Cilag International NV
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Agencia Española de Medicamentos y Productos SanitariosGermany: Ethics CommissionGreat Britain: Medicines and Healthcare Products Regulatory AgencyGermany: Federal Institute for Drugs and Medical DevicesGreat Britain: Research Ethics Committee
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the effectiveness of telaprevir in combination with Peg-IFN-alfa-2a and ribavirin in stable liver transplant patients with chronic hepatitis C virus (HCV) genotype 1.

Description:

This is an open-label (all people know the identity of the intervention), multicenter study in genotype 1 chronic HCV infected liver transplant patients who will be treated for 12 weeks with telaprevir 750 mg every 8 hours given in combination with Peg-IFN-alfa-2a and ribavirin followed by 36 weeks of treatment with Peg-IFN-alfa-2a and ribavirin alone. The total treatment duration will be 48 weeks. Safety will be evaluated throughout the study and will include evaluations of adverse events, clinical laboratory tests, electrocardiogram, vital signs, and physical examination.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 74
• Est. completion date: July 2014
• Est. primary completion date: April 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• First time liver transplant recipient whose primary pre-transplant diagnosis was chronic hepatitis C genotype 1

• More than 6 months to 10 years post-liver transplant

• Patient did or did not receive treatment for HCV prior to liver transplantation

• Patient must agree to have a liver graft biopsy during the screening period unless they had a biopsy within three months of the screening period (for patients between 6 months and one year post transplant) or within six months of the screening period (for patients who are more than one year post transplant)

• A female patient of childbearing potential and a nonvasectomized male patient who has a female partner of childbearing potential must agree to the use of 2 effective methods of birth control from screening until 6 months (female patient) or 7 months (male patient) after the last dose of ribavirin

Exclusion Criteria:

• Patient is currently infected or co-infected with HCV of another genotype than genotype 1

• Patient received treatment for hepatitis C following liver transplantation

• Patient has history of decompensated liver disease or shows evidence of significant liver disease in addition to hepatitis C

• Patient with human immunodeficiency virus or hepatitis B virus co-infection

• Patient with active malignant disease or history of malignant disease within the past 5 years (with the exception of treated basal cell carcinoma or hepatocellular carcinoma)

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Hepatitis C Virus (HCV) Infection
• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C, Chronic
• Hepatitis, Chronic
• Infection

Intervention

Drug:
• Telaprevir
Type=exact number, unit=mg, number=375, form=tablet, route=oral. Patients will receive 2 oral tablets (750 mg) every 8 hours for 12 weeks.
• Pegylated interferon alfa-2a
Type=exact number, unit=µg, number=180, form=injection, route=subcutaneous. 180 microgram (µg) per week, subcutaneous injection, for 48 weeks.
• Ribavirin
Type=exact number, unit=mg, number=200, form=tablet, route=oral. Starting from 600 mg (3 tablets) per day on Day 1. This dose will become higher or lower based on blood results and the investigators opinion (to a goal of 1000 to 1200 mg/day [5 to 6 tablets] based on subject weight), twice daily regimen, for 48 weeks.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Janssen-Cilag International NV

Countries where clinical trial is conducted

Austria,  Belgium,  France,  Germany,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of patients achieving sustained virologic response (SVR) 12 planned	SVR12 planned is defined as having plasma hepatitis C virus (HCV ) ribonucleic acid (RNA) level less than 25 IU/mL 12 weeks after the last planned dose of study medication.	Week 60	No
Secondary	Number of patients achieving SVR12 planned(c)	SVR12 planned(c) is defined as having undetectable plasma HCV RNA levels 12 weeks after the last planned dose of study drugs.	Week 60	No
Secondary	Number of patients achieving SVR24 planned	SVR24 planned is defined as having plasma HCV RNA levels less than 25 IU/mL 24 weeks after the last planned dose of study medication.	Week 72	No
Secondary	Number of patients achieving SVR24 planned(c)	SVR24 planned(c) is defined as having an undetectable plasma HCV RNA level 24 weeks after the last planned dose of study medication.	Week 72	No
Secondary	Number of patients having an undetectable HCV RNA level at Week 4 of treatment		Week 4	No
Secondary	Number of patients having an undetectable HCV RNA level at Week 12 of treatment		Week 12	No
Secondary	Number of patients having undetectable HCV RNA levels at Week 4 and Week 12 of treatment		Week 4 and Week 12	No
Secondary	Number of patients having an undetectable HCV RNA level at the actual end of treatment		Week 48	No
Secondary	Number of patients having an undetectable HCV RNA level at the planned end of treatment		Week 48	No
Secondary	Number of patients having less than 25 IU/mL at the planned end of treatment		Week 48	No
Secondary	Number of patients with on-treatment virologic failure	Virologic failure is defined as patients who meet a virologic stopping rule and/or meet the definition of viral breakthrough.	Week 48	No
Secondary	Number of patients with relapse after undetectable HCV RNA at actual end of treatment	Number of patients who relapse, defined as having confirmed detectable HCV RNA during the follow-up period after previous undetectable HCV RNA (less than 25 IU/mL, target not detected) at actual end of treatment.	Week 48	No
Secondary	Number of patients with relapse after undetectable HCV RNA at planned end of treatment	Number of patients who relapse, defined as having confirmed detectable HCV RNA during the follow-up period after previous undetectable HCV RNA (less than 25 IU/mL, target not detected) at planned end of treatment.	Week 48	No
Secondary	Number of patients with relapse after previous HCV RNA less than 25 IU/mL at planned end of treatment	Number of patients who relapse, defined as having confirmed detectable HCV RNA during the follow-up period after previous HCV RNA less than 25 IU/mL at planned end of treatment.	Week 48	No
Secondary	Number of patients with viral breakthrough	Number of patients with viral breakthrough (defined as an increase more than 1 log in HCV RNA level from the lowest level reached, or a value of HCV RNA more than 100 IU/mL in patients whose HCV RNA has previously become less than 25 IU/mL during treatment).	Week 48	No
Secondary	Change from baseline in log HCV RNA values	Change from baseline in log HCV RNA values at each time point during treatment.	Up to Week 52	No
Secondary	Number of patients who have changes in liver graft biopsy histology		Up to Week 72	No
Secondary	Number of patients with adverse events		Up to Week 72	Yes

External Links

•   Open-Label, Phase 3b Study To Determine Efficacy and Safety of Telaprevir, Pegylated-Interferon-alfa-2a and Ribavirin in Hepatitis C Genotype 1 Infected, Stable Liver Transplant Subjects(18137).