An Efficacy, Pharmacokinetics, Safety and Tolerability Study of TMC435 as Part of a Treatment Regimen for Hepatitis C-Infected Patients

NCT ID: NCT01725529

Last Updated: 2015-08-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 457 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-11-30
• Study Completion Date: 2014-11-30

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).

Conditions

Hepatitis C, Chronic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

TMC435 150 mg

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.

Group Type: EXPERIMENTAL

TMC435

Intervention Type: DRUG

TMC435 100 mg or 150 mg capsules taken orally (by mouth) with food once-daily for 12 weeks (Week 12).

Peginterferon-alpha (PegIFNα-2a)

Intervention Type: DRUG

PegIFNα-2a (180 micrograms \[μg\] once weekly) administered as weekly subcutaneous (s.c.) (under the skin) injections of 0.5 mL for 24 or 48 weeks.

Ribavirin (RBV)

Intervention Type: DRUG

Ribavirin 1000 or 1200 mg/day (taken as 100 mg or 200 mg tablets) depending on body weight (If body weight is \< 75 kg the total daily dose of RBV will be 1000 mg, administered as 400 mg intake with food in the morning and 600 mg intake with food in the evening. If body weight is \> or = 75 kg the total daily dose will be 1200 mg, administered as 2 x 600 mg per intake with food, morning and evening) for 24 or 48 weeks.

TMC435 100 mg

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.

Group Type: EXPERIMENTAL

TMC435

Intervention Type: DRUG

TMC435 100 mg or 150 mg capsules taken orally (by mouth) with food once-daily for 12 weeks (Week 12).

Peginterferon-alpha (PegIFNα-2a)

Intervention Type: DRUG

PegIFNα-2a (180 micrograms \[μg\] once weekly) administered as weekly subcutaneous (s.c.) (under the skin) injections of 0.5 mL for 24 or 48 weeks.

Ribavirin (RBV)

Intervention Type: DRUG

Ribavirin 1000 or 1200 mg/day (taken as 100 mg or 200 mg tablets) depending on body weight (If body weight is \< 75 kg the total daily dose of RBV will be 1000 mg, administered as 400 mg intake with food in the morning and 600 mg intake with food in the evening. If body weight is \> or = 75 kg the total daily dose will be 1200 mg, administered as 2 x 600 mg per intake with food, morning and evening) for 24 or 48 weeks.

Control

Patients will receive placebo once daily (q.d.) plus peginterferon-alpha (PegIFNα-2a) and ribavirin (RBV) for 48 weeks.

Group Type: PLACEBO_COMPARATOR

Peginterferon-alpha (PegIFNα-2a)

Intervention Type: DRUG

PegIFNα-2a (180 micrograms \[μg\] once weekly) administered as weekly subcutaneous (s.c.) (under the skin) injections of 0.5 mL for 24 or 48 weeks.

Ribavirin (RBV)

Intervention Type: DRUG

Ribavirin 1000 or 1200 mg/day (taken as 100 mg or 200 mg tablets) depending on body weight (If body weight is \< 75 kg the total daily dose of RBV will be 1000 mg, administered as 400 mg intake with food in the morning and 600 mg intake with food in the evening. If body weight is \> or = 75 kg the total daily dose will be 1200 mg, administered as 2 x 600 mg per intake with food, morning and evening) for 24 or 48 weeks.

Placebo

Intervention Type: DRUG

Matching placebo capsules taken orally with food once-daily for 48 weeks.

Interventions

TMC435

TMC435 100 mg or 150 mg capsules taken orally (by mouth) with food once-daily for 12 weeks (Week 12).

Intervention Type: DRUG

Peginterferon-alpha (PegIFNα-2a)

PegIFNα-2a (180 micrograms \[μg\] once weekly) administered as weekly subcutaneous (s.c.) (under the skin) injections of 0.5 mL for 24 or 48 weeks.

Intervention Type: DRUG

Ribavirin (RBV)

Ribavirin 1000 or 1200 mg/day (taken as 100 mg or 200 mg tablets) depending on body weight (If body weight is \< 75 kg the total daily dose of RBV will be 1000 mg, administered as 400 mg intake with food in the morning and 600 mg intake with food in the evening. If body weight is \> or = 75 kg the total daily dose will be 1200 mg, administered as 2 x 600 mg per intake with food, morning and evening) for 24 or 48 weeks.

Intervention Type: DRUG

Placebo

Matching placebo capsules taken orally with food once-daily for 48 weeks.

Intervention Type: DRUG

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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen R&D Ireland

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen R&D Ireland Clinical Trial

Role: STUDY_DIRECTOR

Janssen R&D Ireland

Locations

Beijing, , China

Changchun, , China

Changsha, , China

Chengdu, , China

Chongqing, , China

Guangzhou, , China

Hangzhou, , China

Harbin, , China

Jinan, , China

Lanzhou, , China

Nanjing, , China

Shanghai, , China

Shenyang, , China

Tianjin, , China

Wuhan, , China

Zhengzhou, , China

Busan, , South Korea

Chuncheon, Gangwon-Do, , South Korea

Gyeongsangnam-Do, , South Korea

Incheon, , South Korea

Seoul, , South Korea

Countries

China; South Korea

Other Identifiers

TMC435HPC3005

Identifier Type: OTHER

Identifier Source: secondary_id

CR017962

Identifier Type: -

Identifier Source: org_study_id