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

NCT01366638 | Completed Phase 3 Results

• 2 other identifiers: CR017935TMC435HPC3010
• Study Type: interventional
• Target: 79
• Locations: 1 country
• Sites: 11

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of TMC435 in combination with peginterferon alfa-2b and ribavirin in chronic genotype 1 hepatitis C virus (HCV)-infected participants who are treatment-naive or treatment-experienced (prior relapser or non-responder to Interferon-based therapy) in Japan.

Conditions

Hepatitis C, Chronic

Keywords

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

Outcome Measures

Primary Outcomes (10)

• 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).

  Week 36 or 60

• 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).

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

• 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).

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

• 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).

  Up to 48 Weeks

• 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).

  Up to 72 weeks

• 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).

  Up to Week 48

• 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).

  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

• 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).

  Week 24 or 48

• 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).

  Overall (Up to Week 12)

• 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).

  Overall (Up to Week 12)

Study Arms (3)

Treatment-Naive: TMC435 100 mg 12 Wks+PR 24/48

EXPERIMENTAL

Participants will receive TMC435 100 mg once daily with PegIFNa-2b and ribavirin (PR) for 12 weeks (Wks), followed by PR until Week 24 or Week 48. Treatment will be stopped at Week 24 in participants who achieve plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels \<1.2 log10 IU/mL detectable or undetectable at Week 4, and undetectable plasma HCV RNA levels at Week 12. All other participants will continue PR until Week 48.

Drug: TMC435; Drug: Peginterferon alfa-2b (pegIFN alfa-2b); Drug: Ribavirin (RBV)

Prior Relapser: TMC435 100 mg 12 Wks+PR 24/48

EXPERIMENTAL

Participants will receive TMC435 100 mg once daily with PegIFNa-2b and ribavirin (PR) for 12 weeks (Wks) followed by PR until Week 24. Treatment will be stopped at Week 24 in participants who achieve plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels \<1.2 log10 IU/mL detectable or undetectable at Week 4, and undetectable plasma HCV RNA levels at Week 12. All other participants will continue PR until Week 48.

Drug: TMC435; Drug: Peginterferon alfa-2b (pegIFN alfa-2b); Drug: Ribavirin (RBV)

Prior Non-Responder: TMC435 100 mg 12 Wks+PR 48

EXPERIMENTAL

Participants will receive TMC435 100 mg once daily with PegIFNa-2b and ribavirin (PR) for 12 weeks (Wks) followed by PR until Week 48.

Drug: TMC435; Drug: Peginterferon alfa-2b (pegIFN alfa-2b); Drug: Ribavirin (RBV)

Interventions

TMC435 DRUG

100 mg capsule taken by mouth once daily for 12 weeks

Prior Non-Responder: TMC435 100 mg 12 Wks+PR 48; Prior Relapser: TMC435 100 mg 12 Wks+PR 24/48; Treatment-Naive: TMC435 100 mg 12 Wks+PR 24/48

Peginterferon alfa-2b (pegIFN alfa-2b) DRUG

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.

Also known as: PEGINTRON

Prior Non-Responder: TMC435 100 mg 12 Wks+PR 48; Prior Relapser: TMC435 100 mg 12 Wks+PR 24/48; Treatment-Naive: TMC435 100 mg 12 Wks+PR 24/48

Ribavirin (RBV) DRUG

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.

Also known as: REBETOL

Prior Non-Responder: TMC435 100 mg 12 Wks+PR 48; Prior Relapser: TMC435 100 mg 12 Wks+PR 24/48; Treatment-Naive: TMC435 100 mg 12 Wks+PR 24/48

Eligibility Criteria

• Age: 20 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient must have chronic genotype 1 HCV infection with HCV RNA level \>= 5.0 log10 IU/mL
• Patient has never received treatment for HCV (treatment-naive), relapsed after previous IFN-based therapy (prior relapser) or failed to respond to previous IFN-based therapy (non-responder)
• Patient must be willing to use contraceptive measures from the time of informed consent to 6 months after last dose of study medication.

You may not qualify if:

• 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 peg-IFN or ribavirin therapy
• History of, or any current medical condition, which could impact the safety of the patient in the study

Sponsors & Collaborators

• Janssen Pharmaceutical K.K.: lead

Study Sites (11)

Unknown Facility

Amagasaki, Japan

Location

Unknown Facility

Ikeda, Japan

Location

Unknown Facility

Kawasaki, Japan

Location

Unknown Facility

Kumamoto, Japan

Location

Unknown Facility

Niigata, Japan

Location

Unknown Facility

Ohmura, Japan

Location

Unknown Facility

Osaka, Japan

Location

Unknown Facility

Sakai, Japan

Location

Unknown Facility

Sapporo, Japan

Location

Unknown Facility

Suita, Japan

Location

Unknown Facility

Tokyo, Japan

Location

MeSH Terms

Conditions

Hepatitis C, Chronic; Hepatitis C

Interventions

Simeprevir; peginterferon alfa-2b; Ribavirin

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sulfonamides; Sulfones; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Limitations and Caveats

All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated. "Primary" was chosen for each outcome measure because "Exploratory" is not available as an outcome measure type on this form.

Results Point of Contact

• Title: Director
• Organization: Janssen Pharmaceutical K.K., Japan

81 3 44115639

Study Officials

• Janssen Pharmaceutical K.K. Clinical Trial

  Janssen Pharmaceutical K.K.

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 2, 2011
• First Posted: June 6, 2011
• Study Start: May 1, 2011
• Primary Completion: November 1, 2012
• Study Completion: November 1, 2012
• Last Updated: May 5, 2014
• Results First Posted: January 20, 2014

Record last verified: 2014-04

Locations

JP (11)