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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Janssen R&D Ireland
ClinicalTrials.gov Identifier:
NCT01725529
First received: November 9, 2012
Last updated: June 16, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Hepatitis C, Chronic
Drug: TMC435
Drug: Peginterferon-alpha (PegIFNα-2a)
Drug: Ribavirin (RBV)
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Janssen R&D Ireland:

Primary Outcome Measures:
  • The proportion of patients with sustained virologic response (SVR) [ Time Frame: 12 weeks after the planned end of treatment (SVR12) ] [ Designated as safety issue: No ]
    To demonstrate the superiority of TMC435 versus placebo as part of a treatment regimen including peginterferon alfa-2a (PegIFNα-2a) and ribavirin.


Secondary Outcome Measures:
  • The number of patients with sustained virologic response (SVR) [ Time Frame: 24 weeks after the planned end of treatment (SVR24) ] [ Designated as safety issue: No ]
    To demonstrate the superiority of TMC435 versus placebo as part of a treatment regimen including peginterferon alfa-2a (PegIFNα-2a) and ribavirin.

  • The number of patients with sustained virologic response (SVR) [ Time Frame: 72 weeks after the planned end of treatment (SVR72) ] [ Designated as safety issue: No ]
    To demonstrate the superiority of TMC435 versus placebo as part of a treatment regimen including peginterferon alfa-2a (PegIFNα-2a) and ribavirin.

  • Antiviral activity of TMC435 [ Time Frame: Up to Week 72 ] [ Designated as safety issue: No ]
    The antiviral activity over time of TMC435 will be compared to placebo as part of a treatment regimen including PegIFNα-2a and RBV by assessing Hepatitis C virus (HCV) ribonucleic acid (RNA) levels in plasma at different time points.

  • Plasma concentrations of TMC435 [ Time Frame: Up to Week 12 ] [ Designated as safety issue: No ]
    Plasma concentrations of TMC435 will be measured to evaluate pharmacokinetic (PK) parameters of TMC435 and the relationship between TMC435 pharmacokinetics and efficacy and safety parameters.

  • The number of patients in the TMC435 treatment groups who meet the response-guided treatment criteria for the shorter treatment duration [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    To determine the proportion of patients in the TMC435 treatment groups who meet the response-guided treatment criteria for the shorter treatment duration.

  • The number of patients with viral breakthrough [ Time Frame: Up to Week 72 ] [ Designated as safety issue: No ]
    The number of patients who experience viral breakthrough will be determined by measuring Hepatitis C virus (HCV) ribonucleic acid (RNA) levels in plasma.

  • The number of patients with viral relapse [ Time Frame: Up to Week 72 ] [ Designated as safety issue: No ]
    To evaluate the relapse rate after treatment in the TMC435 and placebo treatment groups.

  • The number of patients who experience on-treatment failure in the TMC435 and placebo treatment groups [ Time Frame: Up to Week 72 ] [ Designated as safety issue: No ]
    The number of patients who experience on-treatment failure will be determined by measuring Hepatitis C virus (HCV) ribonucleic acid (RNA) levels in plasma.

  • Changes from baseline in the viral genome sequence of hepatitis C virus (HCV) region NS3/4A in patients not achieving a sustained virologic response (SVR) [ Time Frame: Day 1 (Baseline); Up to Week 72 ] [ Designated as safety issue: No ]
    Viral genome sequencing will be performed on ribonucleic acid (RNA) in plasma samples to monitor for the presence of drug resistant HCV variants.

  • Severity score of fatigue [ Time Frame: Up to Week 72 ] [ Designated as safety issue: No ]
    To compare the severity of fatigue as measured by the Fatigue Severity Scale (FSS) between patients treated with TMC435 versus patients on placebo as part of a treatment regimen including PegIFNα-2a and RBV.

  • The number of patients reporting adverse events as a measure of safety and tolerability [ Time Frame: Up to Week 72 ] [ Designated as safety issue: No ]
  • The number of patients with normalized alanine transaminase (ALT) levels [ Time Frame: Up to Week 72 ] [ Designated as safety issue: No ]
    To determine the proportion of patients with normalized ALT levels at the end of treatment and at the time points of SVR assessment.


Enrollment: 458
Study Start Date: November 2012
Estimated Study Completion Date: November 2014
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: TMC435
TMC435 100 mg or 150 mg capsules taken orally (by mouth) with food once-daily for 12 weeks (Week 12).
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.
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.
Experimental: 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.
Drug: TMC435
TMC435 100 mg or 150 mg capsules taken orally (by mouth) with food once-daily for 12 weeks (Week 12).
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.
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.
Placebo Comparator: Control
Patients will receive placebo once daily (q.d.) plus peginterferon-alpha (PegIFNα-2a) and ribavirin (RBV) for 48 weeks.
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.
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.
Drug: Placebo
Matching placebo capsules taken orally with food once-daily for 48 weeks.

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

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01725529

Locations
China
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
Korea, Republic of
Busan, Korea, Republic of
Chuncheon, Gangwon-Do, Korea, Republic of
Gyeongsangnam-Do, Korea, Republic of
Incheon, Korea, Republic of
Seoul, Korea, Republic of
Sponsors and Collaborators
Janssen R&D Ireland
Investigators
Study Director: Janssen R&D Ireland Clinical Trial Janssen R&D Ireland
  More Information

No publications provided

Responsible Party: Janssen R&D Ireland
ClinicalTrials.gov Identifier: NCT01725529     History of Changes
Other Study ID Numbers: CR017962, TMC435HPC3005
Study First Received: November 9, 2012
Last Updated: June 16, 2014
Health Authority: P.R. China: State Food and Drug Administration, P.R. China

Keywords provided by Janssen R&D Ireland:
Hepatitis C, Chronic
TMC435
Ribavirin
peginterferon-alpha (PegIFNα-2a)

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Hepatitis, Chronic
Ribavirin
Peginterferon alfa-2a
Simeprevir
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Protease Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on August 28, 2014