A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Investigate the Efficacy, Safety and Tolerability of TMC435 vs Placebo as Part of a Treatment Regimen Including Peginterferon α-2a and Ribavirin in Treatment-naïve, Genotype 1 Hepatitis Cinfected Subjects
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Enrollment
- 395
- Primary Endpoint
- The Percentage of Participants Achieving a Sustained Virologic Response 12 Weeks After the Planned End of Treatment (SVR12)
Study Overview
Brief Summary
The purpose of this study is to investigate the effectiveness and safety of TMC435 compared with placebo in participants who are infected with genotype 1 hepatitis C virus who have never received treatment before. Participants will also receive peginterferon alpha-2a and ribavirin as part of their treatment.
Detailed Description
This is a randomized, double-blind (neither physician nor participants know the name of the assigned drug), placebo-controlled study of TMC435 in participants who are infected with genotype 1 hepatitis C virus (HCV), who have never received treatment for HCV infection before. Participants in this study will also receive two other drugs for their HCV infection called peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV). The purpose of the study is to investigate if TMC435 is superior to placebo in reducing plasma levels of HCV ribonucleic acid (RNA) to an undetectable level 12 weeks after the end of treatment. For the first 12 weeks, participants will take either TMC435 or placebo, plus PegIFNα-2a and RBV. For the next 12 weeks, participants will take PegIFN alpha-2a and RBV only. After that, some participants will continue to take PegIFN alpha-2a and RBV for up to 24 additional weeks and some will stop taking PegIFN alpha-2a and RBV depending on response-guided treatment criteria. The study doctor will inform each participant about how to take their study medication and when they should stop taking it. After a participant stops taking study medication, they will continue to come to the doctor's office for study visits until a total of 72 weeks after they enroll in the study. The total duration of the study is 78 weeks (including screening). Participants will be monitored for safety throughout the study.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Care Provider, Investigator)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Genotype 1 hepatitis C infection (confirmed at screening)
- •Patient has not received any prior treatment for hepatitis C
- •Patient must have had a liver biopsy within 3 years before screening (or between the screening and baseline visit) showing chronic hepatitis C infection
- •Must agree to use 2 forms of effective contraception throughout study (both males and females)
Exclusion Criteria
- •Infection with HIV or non genotype 1 hepatitis C
- •Liver disease not related to hepatitic C infection
- •Hepatic decompensation
- •Significant laboratory abnormalities or other active diseases
- •Pregnant or planning to become pregnant
Arms & Interventions
TMC435
TMC435 150 mg capsule once daily for 12 weeks in addition to peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 24 or 48 weeks
Intervention: Peginterferon alpha-2a (PegIFN alpha-2a) (Drug)
Placebo
Placebo 150 mg capsule once daily for 12 weeks in addition to PegIFNα-2a and RBV for 48 weeks
Intervention: Placebo (Drug)
Placebo
Placebo 150 mg capsule once daily for 12 weeks in addition to PegIFNα-2a and RBV for 48 weeks
Intervention: Peginterferon alpha-2a (PegIFN alpha-2a) (Drug)
TMC435
TMC435 150 mg capsule once daily for 12 weeks in addition to peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 24 or 48 weeks
Intervention: TMC435 (Drug)
Placebo
Placebo 150 mg capsule once daily for 12 weeks in addition to PegIFNα-2a and RBV for 48 weeks
Intervention: Ribavirin (RBV) (Drug)
TMC435
TMC435 150 mg capsule once daily for 12 weeks in addition to peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 24 or 48 weeks
Intervention: Ribavirin (RBV) (Drug)
Outcomes
Primary Outcomes
The Percentage of Participants Achieving a Sustained Virologic Response 12 Weeks After the Planned End of Treatment (SVR12)
Time Frame: Week 36 or Week 60
The table below shows the percentage of participants in each treatment group who achieved a SVR12, defined as the percentage of participants with undetectable plasma Hepatitis C virus ribonucleic acid 12 weeks after planned end of treatment.
Secondary Outcomes
- Actual Values of log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)(Day 3, Week 1, Week 4, Week 12, Week 24, and Week 48)
- Time From End-of-treatment to Viral Relapse(Up to Week 72)
- The Percentage of Participants Achieving a Sustained Virologic Response at Week 72 (SVRW72)(Week 72)
- The Percentage of Participants Who Achieved a Sustained Virologic Response 24 Weeks After the Planned End of Treatment (SVR24)(Week 48 or Week 72)
- The Percentage of Participants Who Achieved a Sustained Virologic Response 4 Weeks After the Planned End of Treatment (SVR4)(Week 28 or Week 52)
- Change From Baseline in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)(Day 3, Week 1, Week 4, Week 12, Week 24, and Week 48)
- Percentage of Participants With On-treatment Virologic Response at All Time Points(Day 3, Week 1, Week 2, Week 8, Week 16, Week 20, Week 28, Week 36, and Week 42)
- The Percentage of Participants Achieving a Rapid Virologic Response (RVR)(Week 4)
- The Percentage of Participants Achieving a Early Virologic Response (EVR)(Week 12)
- The Percentage of Participants Achieving a Complete Early Virologic Response (cEVR)(Week 12)
- The Percentage of Participants Achieving a Extended Rapid Virologic Response (eRVR)(Week 4 and 12)
- The Percentage of Participants With <1 log10 Decrease in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) From Baseline at Week 4(Week 4)
- Percentage of Participants With in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels >1000 IU/mL at Week 4(Week 4)
- Percentage of Participants With Null Response(Week 12)
- Percentage of Participants With Partial Response(Week 12)
- Percentage of Participants With Viral Breakthrough(Up to Week 48)
- Percentage of Participants With Viral Relapse(Up to Week 72)
- Percentage of Participants Who Completed All Study Treatment at Week 24 Because of the Treatment Duration Rule(Week 24)
- Percentage of Participants With On-treatment Failure(Week 48)
- Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <25 IU/mL Undetectable or Detectable(Up to Week 48)
- Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <25 IU/mL Undetectable(Up to Week 48)
- Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <100 IU/mL(Up to Week 48)
- Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <1000 IU/mL(Up to Week 48)
- The Percentage of Participants With Viral Breakthrough at Different Time Points(Up to Week 48)
- The Percentage of Participants With Normalization of Alanine Aminotransferase (ALT)(Up to Week 48)
- Median Time to Normalization of Alanine Aminotransferase (ALT) Levels(Up to Week 48)
- Plasma Concentration of TMC435: Area Under the Plasma Concentration-time Curve From the Time of Administration to 24 Hours After Dosing (AUC24h)(Fom the time of administration up to 24 hours after dosing at Weeks 2, 4, 8, and 12)
- Plasma Concentration of TMC435: Predose Plasma Concentration (C0h)(Before administration of TMC435 at Weeks 2, 4, 8, and 12)
- Plasma Concentration of TMC435: Systemic Clearance (CL)(Across Weeks 2, 4, 8, and 12)
- Area Under the Curve From Baseline to Week 60 (AUC60) and Week 72 (AUC72) for the Fatigue Severity Scale (FSS) Total Scores(Baseline to Week 60 and Week 72)
- Area Under the Curve From Baseline to Week 60 (AUC60) and Week 72 (AUC72) for Impairment in Overall Work Productivity Scores Due to Hepatitis C Virus (HCV) Infection and Its Treatment(Baseline to Week 60 and Week 72)
- Area Under the Curve From Baseline to Week 60 (AUC60) and Week 72 (AUC72) for Impairment in Daily Activity Scores Due to Hepatitis C Virus (HCV) Infection and Its Treatment(Baseline to Week 60 and Week 72)
- Area Under the Curve From Baseline to Week 60 (AUC60) and Week 72 (AUC72) in Work Productivity and Activity (WPAI) Absenteeism Scores Due to Hepatitis C Virus (HCV) Infection and Its Treatment(Baseline to Week 60 and Week 72)