An Efficacy, Pharmacokinetics, Safety and Tolerability Study of TMC435 as Part of a Treatment Regimen for Hepatitis C-Infected Patients
- Conditions
- Hepatitis C, Chronic
- Interventions
- Registration Number
- NCT01725529
- Lead Sponsor
- Janssen R&D Ireland
- Brief Summary
The purpose of this study is to provide confirmatory efficacy and safety data of TMC435 as part of a treatment regimen including peginterferon-alpha (PegIFNα-2a) and ribavirin (RBV) in patients with genotype 1 Hepatitis C virus (HCV) infection.
- Detailed Description
This is a multicenter, randomized (study drug is assigned by chance), double-blind (neither sponsor, physician nor patient knows the name of the assigned study drug), Phase III study to compare the efficacy, tolerability and safety of TMC435 (in development for treatment of chronic hepatitis C virus \[HCV\] infection) versus placebo (a preparation containing no drug used as control) as part of a treatment regimen including peginterferon-alpha (PegIFNα-2a) and ribavirin (RBV) (both current therapies for HCV) in adult treatment-naïve patients (patients who have never taken HCV medications) with genotype 1 Hepatitis C virus (HCV) infection. The study will consist of a screening period with a maximum duration of 6 weeks, a response guided 24- or 48-week (TMC435 treatment groups) or 48-week (control group) treatment period, and a post-therapy follow-up period up to 72 weeks after the start of treatment. Patients will be randomly assigned in a 1:1:1 fashion to receive TMC435 or placebo, stratified by HCV genotype 1 subtype and IL28B genotype within each country. In the first 24 weeks, patients will receive 12 weeks TMC435 100 or 150 mg or placebo once-daily (q.d.) plus PegIFNα-2a plus RBV, after which they will continue with PegIFNα-2a and RBV. Response-guided treatment criteria will be used to determine PegIFNα-2a and RBV total treatment duration of 24 or 48 weeks for patients in the TMC435 treatment groups. In the control group, all patients will be required to complete 48 weeks of treatment with PegIFNα-2a and RBV. In all 3 treatment groups, there will be a post-therapy follow-up period up to 72 weeks after the start of treatment. The total study duration for each patient will be a maximum of 78 weeks (including the 6-week screening period).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 457
- A liver biopsy within 3 years prior to the screening visit (or between screening and day of randomization) with histology consistent with chronic Hepatitis C virus (HCV) infection
- Presence of contraindications for a liver biopsy in patients who are otherwise deemed eligible for participation does not exclude the patient from participation
- Genotype 1 HCV infection (confirmed at screening)
- Plasma HCV RNA of > 10,000 IU/mL at screening
- Prior treatment with any approved or investigational drug for the treatment of hepatitis C
- Co-infection with hepatitis B virus or human immunodeficiency virus (HIV)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description TMC435 150 mg Ribavirin (RBV) Patients will receive 12 weeks TMC435 150 mg once daily (q.d.) plus peginterferon-alpha (PegIFNα-2a) and ribavirin (RBV), followed by PegIFNα-2a and RBV alone. Response-guided treatment criteria will be used to determine total treatment duration of 24 or 48 weeks for patients in the TMC435 treatment groups. Patients in the control group will continue to receive treatment with PegIFNα-2a and RBV until Week 48. TMC435 100 mg Ribavirin (RBV) Patients will receive 12 weeks TMC435 100 mg once daily (q.d.) plus peginterferon-alpha (PegIFNα-2a) and ribavirin (RBV), followed by PegIFNα-2a and RBV alone. Response-guided treatment criteria will be used to determine total treatment duration of 24 or 48 weeks for patients in the TMC435 treatment groups. Patients in the control group will continue PegIFNα-2a and RBV until Week 48. TMC435 150 mg TMC435 Patients will receive 12 weeks TMC435 150 mg once daily (q.d.) plus peginterferon-alpha (PegIFNα-2a) and ribavirin (RBV), followed by PegIFNα-2a and RBV alone. Response-guided treatment criteria will be used to determine total treatment duration of 24 or 48 weeks for patients in the TMC435 treatment groups. Patients in the control group will continue to receive treatment with PegIFNα-2a and RBV until Week 48. TMC435 150 mg Peginterferon-alpha (PegIFNα-2a) Patients will receive 12 weeks TMC435 150 mg once daily (q.d.) plus peginterferon-alpha (PegIFNα-2a) and ribavirin (RBV), followed by PegIFNα-2a and RBV alone. Response-guided treatment criteria will be used to determine total treatment duration of 24 or 48 weeks for patients in the TMC435 treatment groups. Patients in the control group will continue to receive treatment with PegIFNα-2a and RBV until Week 48. TMC435 100 mg TMC435 Patients will receive 12 weeks TMC435 100 mg once daily (q.d.) plus peginterferon-alpha (PegIFNα-2a) and ribavirin (RBV), followed by PegIFNα-2a and RBV alone. Response-guided treatment criteria will be used to determine total treatment duration of 24 or 48 weeks for patients in the TMC435 treatment groups. Patients in the control group will continue PegIFNα-2a and RBV until Week 48. TMC435 100 mg Peginterferon-alpha (PegIFNα-2a) Patients will receive 12 weeks TMC435 100 mg once daily (q.d.) plus peginterferon-alpha (PegIFNα-2a) and ribavirin (RBV), followed by PegIFNα-2a and RBV alone. Response-guided treatment criteria will be used to determine total treatment duration of 24 or 48 weeks for patients in the TMC435 treatment groups. Patients in the control group will continue PegIFNα-2a and RBV until Week 48. Control Peginterferon-alpha (PegIFNα-2a) Patients will receive placebo once daily (q.d.) plus peginterferon-alpha (PegIFNα-2a) and ribavirin (RBV) for 48 weeks. Control Ribavirin (RBV) Patients will receive placebo once daily (q.d.) plus peginterferon-alpha (PegIFNα-2a) and ribavirin (RBV) for 48 weeks. Control Placebo Patients will receive placebo once daily (q.d.) plus peginterferon-alpha (PegIFNα-2a) and ribavirin (RBV) for 48 weeks.
- Primary Outcome Measures
Name Time Method Percentage of Participants With Sustained Virologic Response 12 Weeks After End of Study Drug Treatment (SVR12) 12 weeks after the end of treatment (EOT: Week 24 or 48) Participants considered to have achieved SVR12 if both conditions are met: 1). the hepatitis C virus ribonucleic acid (HCV RNA) is less than (\<) lower limit of quantification (LLOQ; 25 international unit per milliliter \[IU/mL\]) undetectable at end of treatment and, 2). the HCV RNA is \< LLOQ detectable or undetectable at 12 weeks after the planned end of study drug treatment.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With Sustained Virologic Response 24 Weeks After End of Study Drug Treatment (SVR24) 24 weeks after the end of treatment (EOT: Week 24 or 48) Participants considered to have achieved SVR24 if both conditions are met: 1). the hepatitis C virus ribonucleic acid (HCV RNA) is less than (\<) lower limit of quantification (LLOQ;25 IU/mL) undetectable at end of treatment and, 2). the HCV RNA is \< LLOQ detectable or undetectable at 24 weeks after the planned end of study drug treatment.
Percentage of Participants With Sustained Virologic Response at Week 72 (SVRW72) Week 72 Percentage of Participants With On-treatment Failure End of Treatment (EOT: Week 24 or 48) A participant with on-treatment failure refers to a participant with confirmed detectable HCV RNA at the end of treatment.
Percentage of Participants With Viral Breakthrough Week 24 or 48 (End of Treatment) The number of patients who experience viral breakthrough will be determined by measuring Hepatitis C virus (HCV) ribonucleic acid (RNA) levels in plasma. Viral breakthrough was defined as a confirmed increase of \>1 log10 IU/mL in HCV RNA level from the lowest level reached, or a confirmed HCV RNA level of \>100 IU/mL in subjects whose HCV RNA levels had previously been below the limit of quantification (\<25 IU/mL detectable) or undetectable (\<25 IU/mL undetectable) while on study treatment.
Percentage of Participants With Viral Relapse 72 weeks after the EOT (Week 24 or 48) Viral relapse was defined as undetectable HCV RNA at the actual end of treatment and last HCV RNA measurement during follow-up ≥25 IU/mL.
Percentage of Participants With On-treatment Normalization of Alanine Aminotransferase Level 72 weeks after the EOT (Week 24 or 48) Percentage of participants with on-treatment normalization of alanine aminotransferase level were assessed.