Clinical trial NCT01725529: An Efficacy, Pharmacokinetics, Safety and Tolerability Study of TMC435 as Part of a Treatment Regimen for Hepatitis C-Infected Patients
Official title: A Phase III, Randomized, Double-Blind, Placebo-Controlled Study to Investigate the Efficacy, Pharmacokinetics, Safety and Tolerability of TMC435 vs. Placebo as Part of a Treatment Regimen Including Peginterferon Alfa-2a and Ribavirin in Treatment-Naïve, Genotype 1 Hepatitis C-Infected Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hepatitis C, Chronic
Keywords: Hepatitis C, Chronic
TMC435
Ribavirin
peginterferon-alpha (PegIFNα-2a)
Lead sponsor: Janssen R&D Ireland
Sponsor class: INDUSTRY
First posted: 2012-11-14
Enrollment: 457
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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)

Primary outcomes:
measure: Percentage of Participants With Sustained Virologic Response 12 Weeks After End of Study Drug Treatment (SVR12)
timeFrame: 12 weeks after the end of treatment (EOT: Week 24 or 48)
Secondary outcomes:
measure: Percentage of Participants With Sustained Virologic Response 24 Weeks After End of Study Drug Treatment (SVR24)
timeFrame: 24 weeks after the end of treatment (EOT: Week 24 or 48)
measure: Percentage of Participants With Sustained Virologic Response at Week 72 (SVRW72)
timeFrame: Week 72
measure: Percentage of Participants With On-treatment Failure
timeFrame: End of Treatment (EOT: Week 24 or 48)
measure: Percentage of Participants With Viral Breakthrough
timeFrame: Week 24 or 48 (End of Treatment)
measure: Percentage of Participants With Viral Relapse
timeFrame: 72 weeks after the EOT (Week 24 or 48)
measure: Percentage of Participants With On-treatment Normalization of Alanine Aminotransferase Level
timeFrame: 72 weeks after the EOT (Week 24 or 48)
Other outcomes:
Locations:
city: Beijing
country: China
city: Changchun
country: China
city: Changsha
country: China
city: Chengdu
country: China
city: Chongqing
country: China
city: Guangzhou
country: China
city: Hangzhou
country: China
city: Harbin
country: China
city: Jinan
country: China
city: Lanzhou
country: China
city: Nanjing
country: China
city: Shanghai
country: China
city: Shenyang
country: China
city: Tianjin
country: China
city: Wuhan
country: China
city: Zhengzhou
country: China
city: Busan
country: Korea, Republic of
city: Chuncheon, Gangwon-Do
country: Korea, Republic of
city: Gyeongsangnam-Do
country: Korea, Republic of
city: Incheon
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
Study officials:
affiliation: Janssen R&D Ireland
name: Janssen R&D Ireland Clinical Trial
role: STUDY_DIRECTOR
References: