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 Hepatitis C, Genotype 1 Infected Subjects Who Relapsed After Previous Interferon-based Therapy
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Enrollment
- 394
- 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 patients who are infected with genotype 1 hepatitis C virus who relapsed after previous interferon-based therapy. Patients will also receive peginterferon alfa-2a and ribavirin as part of their treatment.
Detailed Description
This is a randomized, double-blind (neither physician nor patients knows the name of the assigned drug), placebo-controlled study of TMC435 in patients who are infected with genotype 1 hepatitis C virus who relapsed after previous interferon-based therapy. Patients in this study will also receive two other drugs for their infection called peginterferon alfa-2a and ribavirin. The purpose of the study is to investigate if TMC435 is superior to placebo in reducing hepatitis C virus to an undetectable level 24 weeks after the end of treatment. For the first 12 weeks, patients will take TMC435 or placebo, plus peginterferon alfa-2a and ribavirin. For the next 12 weeks, patients will take peginterferon alfa-2a and ribavirin only. After that, some patients will continue to take peginterferon alfa-2a and ribavirin for up to 24 additional weeks. Other patients will stop taking peginterferon alfa-2a and ribavirin. The study doctor will inform each patient about how to take their study medication and when they should stop taking it. After a patient 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). Patients will be monitored for safety throughout the study. Study assessments at each study visit may include but are not limited to: blood and urine collection for testing, ECG assessments (a measurement of the electrical activity of your heart), patient questionnaires, and physical examinations TMC435 will be taken as an oral capsule of 150 mg once per day. Peginterferon (Pegasys ®) will be given as an injection of 180 µg once each week. Ribavirin (Copegus ®) will be taken as a tablet twice each day and the dose will depend on your body weight.
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)
- •Have previously received peginterferon-based therapy for at least 24 weeks with documented HCV RNA at last measurement and relapsed within 1 year of last taking medication
- •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
Placebo
Placebo 150 mg capsule once daily for 12 weeks in addition to peginterferon alfa-2a and ribavirin 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 alfa-2a and ribavirin 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 peginterferon alfa-2a and ribavirin for 48 weeks
Intervention: Placebo (Drug)
Placebo
Placebo 150 mg capsule once daily for 12 weeks in addition to peginterferon alfa-2a and ribavirin for 48 weeks
Intervention: Ribavirin (RBV) (Drug)
TMC435
TMC435 150 mg capsule once daily for 12 weeks in addition to peginterferon alfa-2a and ribavirin for 24 or 48 weeks
Intervention: Ribavirin (RBV) (Drug)
TMC435
TMC435 150 mg capsule once daily for 12 weeks in addition to peginterferon alfa-2a and ribavirin for 24 or 48 weeks
Intervention: TMC435 (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
- 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)
- Actual Values of log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)(Day 3, Week 1, Week 4, Week 12, Week 24, and Week 48)
- The 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 Week 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)
- The Percentage of Participants With Null Response(Week 12)
- The Percentage of Participants With Partial Response(Week 12)
- The Percentage of Participants With Viral Breakthrough(Up to Week 48)
- The Percentage of Participants With Viral Relapse(Up to Week 72)
- The Percentage of Participants Who Completed All Study Treatment at Week 24 Because of the Treatment Duration Rule(Week 24)
- The Percentage of Participants With On-treatment Failure(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) <25 IU/mL Undetectable or Detectable(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)
- Time From End-of-treatment to Viral Relapse(Up to Week 72)
- 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)(From the time of administration up to 24 hours after dosing through Week 12)
- Plasma Concentration of TMC435: Predose Plasma Concentration (C0h)(Before administration of TMC435 through Week 12)
- Plasma Concentration of TMC435: Systemic Clearance (CL)(From the time of administration through Week 12)