A Study of TMC435 in Genotype 1, Hepatitis C-infected Patients Who Relapsed After Previous Interferon (IFN)-Based Therapy

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of TMC435 in combination with peginterferon alfa-2a (PegIFNα-2a) and ribavirin in genotype 1 hepatitis C virus (HCV)-infected participants who relapsed after previous interferon (IFN)-based therapy in Japan.

Detailed Description
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This is a single-arm study to evaluate the efficacy and safety of TMC435 in combination with the standard of care (SoC), PegIFNα-2a (P) and ribavirin (R), in adult, genotype 1 HCV-infected participants who relapsed after previous IFN-based therapy in Japan. The study objective is to evaluate the efficacy of TMC435 by the percentage of participants with undetectable HCV ribonucleic acid (RNA). Participants will receive 12 weeks of treatment with TMC435 (100 mg) once daily plus PR followed by 12 or 36 weeks of treatment with PR. TMC435 is a 100-mg capsule and will be taken orally (via the mouth). Treatment with PR will last 24 or 48 weeks. Pegylated interferon is supplied as a vial containing 1.0 mL solution with 180 µg PegIFNα-2a and will be injected by a syringe under the skin once weekly. Ribavirin is given as 200-mg tablets (daily dose: 600-1000 mg), taken orally two times a day after meals. The participants will receive oral capsules of TMC435 (100 mg) once daily up to Week 12.

Official Title
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A Phase III, Open-label Trial in Japan to Investigate the Efficacy and Safety of TMC435 as Part of a Treatment Regimen Including Peginterferon Alfa-2a and Ribavirin in Genotype 1, Hepatitis C-infected Subjects Who Relapsed After Previous IFN-based Therapy

Conditions
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Hepatitis C, Chronic

Intervention / Treatment
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* Drug: TMC435
* Drug: Pegylated interferon (pegIFN alpha-2a)
* Drug: Ribavirin (RBV)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must have chronic genotype 1 HCV with HCV RNA level >= 5.0 log10 IU/mL Participant relapsed after previous IFN-based therapy Participant must be willing to use contraceptive measures from the time of informed consent to 6 months after last dose of study medication. Exclusion Criteria: Co-infection with any other HCV genotype or co-infection with the human immunodeficiency virus (HIV) Diagnosed with hepatic cirrhosis or hepatic failure A medical condition which is a contraindication to pegIFN or ribavirin therapy History of, or any current medical condition, which could impact the safety of the patient in the study

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TMC435 100 mg 12 Wks + PR24/48<br>Participants will receive TMC435 100 mg once daily with PegIFNα-2a and ribavirin (PR) for 12 weeks (Wks) followed by PR until Week 24 (PR 24). Treatment will be stopped at Week 24 in participants who achieve plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels less than (<) 1.2 log10 IU/mL detectable or undetectable of at Week 4, and undetectable HCV RNA levels at Week 12. All other participants will continue PR until Week 48 (PR 48). | Drug: TMC435<br>* 100-mg capsule once daily for 12 weeks<br>Drug: Pegylated interferon (pegIFN alpha-2a)<br>* 180 mcg injected subcutaneously (by a syringe under the skin) once weekly for 12 to 36 weeks (or until Week 48).<br>* Other names: PEGASYS;Drug: Ribavirin (RBV)<br>* 200-mg tablets (daily dose: 600-1000 mg) taken orally (by mouth) two times a day for 12 to 36 weeks (or until Week 48).<br>* Other names: COPEGUS;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Percentage of Participants With a Sustained Virologic Response 12 Weeks After the Actual End of Treatment (SVR12) | The table below shows the percentage of participants with an SVR12 defined as participants with undetectable plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) at the end of treatment (Week 24 or 48) who also had undetectable plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) 12 weeks after the last dose of treatment (Week 36 or 60). | Week 36 or 60 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Percentage of Participants With a Sustained Virologic Response 24 Weeks After the Actual End of Treatment (SVR24) | The table below shows the percentage of participants with a SVR24 defined as participants with undetectable plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) at the end of treatment (Week 24 or 48) and at 24 weeks after the last dose of treatment (Week 48 or 72). | Week 48 or 60 | 
| The Percentage of Participants Who Achieved a Greater Than or Equal to 2 log10 IU/mL Drop From Baseline in Plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) at Each Time Point During Treatment and Follow-up | The table below shows the percentage of participants with greater than or equal to 2 log10 IU/mL drop from baseline in plasma HCV RNA at each time point during treatment, at the end of treatment (Week 24 or 48), and post-treatment follow-up. | Days 3 and 7, Weeks 2, 3, 4, 8, 12, 16, 20, 24, 28, 36, 48, 60, 72, EOT, and follow-up (FU) Weeks 4, 12, and 24 | 
| The Percentage of Participants With Undetectable Plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) During Treatment and at the End of Treatment (EOT) | The table below shows the percentage of participants with undetectable HCV RNA (defined as less than 1.2 log10 IU/mL during treatment at Weeks 4, 12, 24, 36, 48, 60, 72, and at EOT [Week 24 or 48]). | Weeks 4, 12, 24, 36, 48, 60, 72, and at EOT | 
| The Number of Participants With Viral Breakthrough | Viral breakthrough was defined as a confirmed increase of greater than 1 log10 IU/mL in plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels from the lowest level reached or a confirmed value of plasma HCV RNA of > 2.0 log10 IU/mL in particpants whose plasma HCV RNA level had previously been below 1.2 log10 IU/mL detectable or undetectable during the treatment period. The table below shows that no viral breakthrough was noted in any participants during the treatment period of the study. | Day 1 until end of treatment (EOT [Week 24 or 48]) | 
| The Number of Participants Demonstrating Viral Relapse | The table below shows the number of participants who demonstrated viral relapse, defined as undetectable Hepatitis C Virus Ribonucleic Acid (HCV RNA) at end of treatment (EOT) and detectable HCV RNA during follow-up or detectable HCV RNA at the time points of sustained virologic response (SVR) assessment . The incidence of viral relapse was calculated for participants with undetectable HCV RNA levels at EOT and with at least one follow-up HCV RNA measurement. | Up to 72 weeks | 
| Plasma Concentrations of TMC435 | The table below shows median (range) TMC435 predose plasma concentration (C0h) values and the TMC435 maximum plasma concentration (Cmax) values for all participants who received TMC435 for up to 12 weeks. Overall is the median exposure estimate using all available data for each participant in the study.Sparse blood samples were collected during the study (blood sampling times were 3 and 5 hours post- dose at Week 2 and Week 8 and pre-dose and 2 hours post-dose at Week 4 and Week 12). | Overall (blood sampling times were 3 and 5 hours post- dose at Week 2 and Week 8 and pre-dose and 2 hours post-dose at Week 4 and Week 12) | 
| Area Under the Plasma Concentration-time Curve From 0 to 24 Hrs (AUC24h) for TMC435 | The table below shows the median (range) AUC24h values for TMC435 for all participants who received TMC435 for up to 12 weeks. Overall is the median exposure estimate using all available data for each participant in the study. Sparse blood samples were collected during the study (blood sampling times were 3 and 5 hours post- dose at Week 2 and Week 8 and pre-dose and 2 hours post-dose at Week 4 and Week 12). | Overall (blood sampling times were 3 and 5 hours post- dose at Week 2 and Week 8 and pre-dose and 2 hours post-dose at Week 4 and Week 12) | 
| The Number of Participants With Abnormal Alanine Aminotransferase (ALT) Levels at Baseline Who Achieved Normal ALT Levels at the End of Treatment (EOT) | The table below shows the number of participants with abnormal ALT levels at baseline (Day 1) who achieved normalization of ALT levels (defined as an ALT value less than or equal to the Upper Limit of Normality [ie, 40 IU/mL] at EOT). At baseline, 15/49 participants had abnormal ALT levels. | EOT (Week 24 or 48) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatitis C, Chronic, Hepatitis C virus, Interferon Alfa-2a, Ribavirin, Viral RNA