A Study of TMC435 in Participants With Genotype 1 Hepatitis C Virus (HCV) Infection

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

• Ages 20 to 70 years
• All sexes
• No healthy volunteers
• Adult, Older adult

Trial locations and contacts

11 sites in 1 country.

About this study

Official title: A Phase III, Open-Label Study in Japan to Assess the Efficacy and Safety of TMC435 as Part of a Treatment Regimen Including Peginterferon Alfa-2b and Ribavirin in Hepatitis C, Genotype 1 Infected Subjects

Conditions

Hepatitis C, Chronic

Being tested

TMC435, Peginterferon alfa-2b (pegIFN alfa-2b), Ribavirin (RBV)

Keywords

Hepatitis C, Chronic, TMC435, Hepatitis C, Hepatitis C virus, Interferon Alfa-2b, Ribavirin, Viral ribonucleic acid

Medical subject headings

Hepatitis C, Chronic, Hepatitis C

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

• TMC435Drug

  100 mg capsule taken by mouth once daily for 12 weeks

• Peginterferon alfa-2b (pegIFN alfa-2b)Drug

  Also called PEGINTRON

  PegIFN alfa-2b will be supplied as a vial containing dried and frozen powder with 74,148 or 222 mcg pegIFN alpha-2b attached to 0.7 ml injection water (50, 100 or 150 mcg/0.5mL pegIFN alpha-2b) and will be administered according to the manufacturer's prescribing information as 1.5 mcg/kg once weekly injected subcutaneous (under the skin) for up to 24-48 weeks.

• Ribavirin (RBV)Drug

  Also called REBETOL

  The dose of RBV given will be based on body weight. If body weight is > 80 kg the total daily dose of RBV will be 1000 mg, taken by mouth as 400 mg (2 capsules of 200 mg) after breakfast and 600 mg (3 capsules of 200 mg) after supper. If body weight is > 60 kg to <=80 kg the total daily dose will be 800 mg, taken by mouth as 400 mg (2 capsules of 200 mg per intake) after breakfast and supper. If body weight is <=60 kg the total daily dose of RBV will be 600 mg, taken by mouth as 200 mg (1 capsule of 200 mg) after breakfast and 400 mg (2 capsules of 200 mg) after supper. Total duration of RBV will be 24-48 weeks.

What is being measured

The primary outcome is the main question the study is designed to answer.

1. 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 in each treatment group with an SVR12 defined as participants with undetectable plasma Hepatitis C virus (HCV) ribonucleic acid (RNA) at the end of treatment (Week 24 or 48) who also had undetectable plasma HCV RNA 12 weeks after the last dose of treatment (Week 36 or 60). NOTE: All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated (refer to Limits and Caveats).

   Measured: Week 36 or 60

2. 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 in each treatment group with a SVR24 defined as participants with undetectable plasma hepatitis C virus (HCV) ribonucleic acid (RNA) at the end of treatment and at 24 weeks after the last dose of treatment (Week 48 or 72). NOTE: All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated (refer to Limits and Caveats).

   Measured: 24 weeks after the last dose of treatment (Week 48 or 72)

3. The Percentage of Participants With Undetectable Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) During Treatment and at the End of Treatment

   The table below shows the percentage of participants in each treatment group with undetectable HCV RNA less than 1.2 log10 IU/mL during treatment and at end of treatment (EOT). NOTE: All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated (refer to Limits and Caveats).

   Measured: Weeks 4, 12, 24, 36, 48, 60, 72, and EOT (up to Week 48)

4. The Number of Participants With Viral Breakthrough

   The table below shows the number of participants in each treatment group who experienced viral breakthrough during the TMC435 treatment period. Viral breakthrough is defined as a confirmed increase of greater than 1 log10 IU/mL in plasma hepatitis C virus (HCV) ribonucleic acid (RNA) level from the lowest level reached or a confirmed value of plasma HCV RNA of greater than 2.0 log10 IU/mL in participants whose plasma HCV RNA level had previously been reported below 1.2 log10 IU/mL detectable or undetectable. NOTE: All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated (refer to Limits and Caveats).

   Measured: Up to 48 Weeks

5. The Number of Participants Demonstrating Viral Relapse

   The table below shows the number of participants in each treatment group who demonstrated viral relapse, defined as having undetectable plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels at end of treatment (EOT [Week 24 or 48]) and detectable HCV RNA during follow-up or detectable HCV RNA at the time points of an assessment of sustained virologic response (SVR). The number of participants analyzed in each treatment group below are those with undetectable HCV RNA levels at EOT and with at least one follow-up HCV RNA measurement. NOTE: All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated (refer to Limits and Caveats).

   Measured: Up to 72 weeks

6. The Number of Participants With Abnormal Alanine Aminotransferase (ALT) Levels at Baseline Who Achieved Normal Limit of ALT at the End of Treatment (EOT)

   The table below shows the number of participants in each treatment group with abnormal ALT levels at Baseline who achieved normalization of ALT levels defined as having an ALT value less than or equal to the Upper Limit of Normality (ie, 40 IU/mL) at EOT. At Baseline, 15 treatment-naïve participants, 13 prior relapsers, and 13 prior non-responders had abnormal ALT levels at Baseline. NOTE: All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated (refer to Limits and Caveats).

   Measured: Up to Week 48

7. 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 in each treatment group with greater than or equal to 2 log10 IU/mL drop from baseline in plasma hepatitis C virus (HCV) ribonucleic acid (RNA) at each time point during treatment and post-treatment follow-up. NOTE: All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated (refer to Limits and Caveats).

   Measured: Day 3, Day 7 and Weeks 2, 3, 4, 8, 12, 16, 20, 24, 28, 36, 48, 60, 72, EOT (up to Week 24 or 48), follow-up (FU) Week 4, 12, and 24

8. The Percentage of Participants Who Met Response Guided Treatment (RGT) Criteria and Completed Treatment With Peginterferon Alpha-2b (PegIFNα-2b) and Ribavirin (RBV) at Week 24

   The table below shows the percentage of participants in each treatment group who met RGT criteria (ie, who had plasma levels of hepatitis C virus ribonucleic acid [HCV RNA] <1.2 log10 IU/mL detectable/undetectable at Week 4 and <1.2 log 10 IU/mL undetectable at Week 12) and completed treatment with PegIFNα-2b and RBV at Week 24. Participants in the TMC435 Treatment-Naïve and TMC435 Prior Relapser treatment groups not meeting RGT criteria continued treatment with PegIFNα-2a and RBV to Week 48 (does not apply to the TMC435 Non-responder treatment group because the specified treatment duration was 48 weeks and RGT criteria was not assessed at Week 24). NOTE: All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated (refer to Limits and Caveats).

   Measured: Week 24 or 48

9. The Area Under the Plasma Concentration-Time Curve (From 0 to 24 Hours) (AUC24h)

   The table below shows the median (range) AUC24h values for TMC435 for all participants in each TMC435 treatment group who received TMC435 for up to 12 weeks. "Overall" is the median exposure estimate using all available data for each participant in the study. NOTE: All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated (refer to Limits and Caveats).

   Measured: Overall (Up to Week 12)

10. Plasma Concentrations of TMC435

    The table below shows the median (range) TMC435 predose plasma concentrations (C0h) and maximum concentration (Cmax) values for participants in each treatment group. "Overall" is the median exposure estimate using all available data for each participant in the study. NOTE: All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated (refer to Limits and Caveats).

    Measured: Overall (Up to Week 12)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1. First posted6 Jun 2011 (estimated)
2. Study startMay 2011
3. Primary completionNov 2012
4. Study completionNov 2012

Resources

• Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
• Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
• Other trials for Hepatitis C, ChronicStudies of the same condition, open and under way.
• What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.