A Phase III Study of TMC435 in Treatment-naive, Genotype 1, Hepatitis C-infected Patients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Janssen Pharmaceutical K.K.
ClinicalTrials.gov Identifier:
NCT01292239
First received: February 1, 2011
Last updated: December 16, 2013
Last verified: December 2013
  Purpose

The purpose of this study is to evaluate the efficacy and safety of TMC435 compared with placebo in combination with peginterferon alfa-2a (pegIFN alfa-2a) and ribavirin in treatment-naive patients with chronic genotype 1 hepatitis C virus (HCV) infection in Japan.


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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Phase III, Randomized, Double-blind, Placebo-controlled Trial in Japan to Investigate the Efficacy and Safety of TMC435 vs. Placebo as Part of a Treatment Regimen Including Peginterferon Alfa-2a and Ribavirin in Treatment-Naive, Genotype 1, Hepatitis C-infected Subjects

Resource links provided by NLM:


Further study details as provided by Janssen Pharmaceutical K.K.:

Primary Outcome Measures:
  • The Percentage of Participants With a Sustained Virologic Response at the End of Treatment (EOT) and 12 Weeks After the Last Dose of Treatment (SVR12) [ Time Frame: EOT (up to Week 24 or 48) and 12 weeks after the EOT (up to Week 36 or 60) ] [ Designated as safety issue: No ]
    The table below shows the observed percentage of participants with a SVR12 defined as undetectable plasma hepatitis C virus (HCV) ribonucleic acid (RNA) at EOT (Week 24 or 48) and at 12 weeks after the last dose of treatment (Week 36 or 60).


Secondary Outcome Measures:
  • The Percentage of Participants With a Sustained Virologic Response at the End of Treatment (EOT) and 24 Weeks After the Last Dose of Treatment (SVR24) [ Time Frame: EOT (up to Week 24 or 48) and 24 weeks after the after the last dose of treatment (up to Week 48 or 72) ] [ Designated as safety issue: No ]
    The table below shows the observed percentage of participants with a SVR24 defined as undetectable plasma hepatitis C virus (HCV) ribonucleic acid (RNA) at the end of treatment (EOT, defined as up to Week 24 or 48) and at 24 weeks after the last dose of treatment (up to Week 48 or 72).

  • The Percentage of Participants Who Achieved a Greater Than or Equal to 2 log10 IU/mL Drop From Baseline in Plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) at Each Time Point During Treatment and Follow-up [ Time Frame: Day 3, Day 7 and Weeks 2, 3, 4, 8, 12, 16, 20, 24, 28, 36, 42, 48, 52, 60, 72, EOT (up to Week 24 or 48), FU Week 4, 12, and 24 ] [ Designated as safety issue: No ]
    The table below shows the percentage of participants with greater than (>) or equal to (=) 2 log10 IU/mL drop from baseline in plasma levels of HCV RNA at each time point during treatment and post-treatment follow-up (FU).

  • The Percentage of Participants With Undetectable Plasma Levels of Hepatitis C Virus Ribonucleic Acid (HCV RNA) During Treatment and at the End of Treatment (EOT) [ Time Frame: Weeks 4, 12, 24, 36, 48, 60, 72, and at EOT (up to Week 24 or 48) ] [ Designated as safety issue: No ]
    The table below shows the percentage of participants with undetectable plasma levels of HCV RNA <1.2 log10 IU/mL during treatment at Weeks 4, 12, 24, 36, 48, 60, 72, and at the EOT (up to Week 24 or 48).

  • The Number of Participants With Viral Breakthrough [ Time Frame: Up to EOT (up to Week 24 or 48) ] [ Designated as safety issue: No ]
    Viral breakthrough was defined as a confirmed increase of > 1 log10 IU/mL in plasma levels of hepatitis C virus (HCV) ribonucleic acid (RNA)l from the lowest level reached or a confirmed value of plasma HCV RNA of > 2.0 log10 IU/mL in participants whose plasma HCV RNA level had previously been below 1.2 log10 IU/mL detectable or undetectable during the treatment period (up to the end of treatment [EOT]).

  • The Number of Participants Demonstrating Viral Relapse [ Time Frame: Up to Week 72 ] [ Designated as safety issue: No ]
    The table below shows the number of participants who demonstrated viral relapse, defined as undetectable plasma levels of hepatitis C virus (HCV) ribonucleic acid (RNA) at the End of Treatment (EOT) (up to Week 24 or 48) and detectable HCV RNA during follow-up or detectable plasma levels of HCV RNA at the time points of sustained virologic response (SVR) assessment. The incidence of viral relapse was only calculated for participants with undetectable plasma levels of HCV RNA at the EOT and with at least one follow-up HCV RNA. measurement.

  • The Number of Participants With Abnormal Alanine Aminotransferase (ALT) Levels at Baseline Who Achieved Normal ALT Levels at the End of Treatment (EOT) [ Time Frame: Baseline (Day 1) to EOT (up to Week 24 or 48) ] [ Designated as safety issue: No ]
    The table below shows the number of participants with abnormal ALT levels at Baseline (Day 1) who achieved normal ALT levels at the EOT (up to Week 24 or 48). At Baseline, 61/123 participants in the TMC435 treatment group and 25/60 participants in the Placebo treatment group had abnormal ALT levels. At the EOT, 47 (77.0%) participants in the TMC435 treatment group and 18 (72.0%) participants in the Placebo treatment group had ALT levels that returned to normal (or normalization of ALT levels defined as an ALT value less than or equal to the Upper Limit of Normality [ie, 40 IU/mL] at EOT.).

  • The Percentage of Participants in the TMC435 Treatment Group Who Met Response Guided Treatment (RGT) Criteria and Completed Treatment With Peginterferon Alpha-2a (PegIFN Alpha-2a) and Ribavirin (RBV) at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    The table below shows the percentage of participants in the TMC435 treatment group who met RGT criteria (ie, who had plasma levels of hepatitis C virus ribonucleic acid [HCV RNA] <1.2 log10 IU/mL detectable/undetectable at Week 4 and <1.2 log 10 IU/mL undetectable at Week 12) and completed treatment with pegIFN alpha 2a and RBV at Week 24. Participants in the TMC435 treatment group not meeting RGT criteria and participants in the placebo group continued treatment with PegIFN alpha 2a and RBV to Week 48.

  • Plasma Concentrations of TMC435 [ Time Frame: Overall (ie, Up to Week 12) ] [ Designated as safety issue: No ]
    The table below shows median (range) predose plasma concentration (C0h) values and median (range) maximum plasma concentration (Cmax) values for TMC435 for all participants in the TMC435 treatment group. The time frame of "Overall" (up to Week 12) represents the median exposure estimate using all available data for each participant in the study.

  • Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC24h) for TMC435 [ Time Frame: Overall (Up to Week 12) ] [ Designated as safety issue: No ]
    The table below shows the median (range) AUC24h values for TMC435 for all participants in the TMC435 treatment group who received TMC435 for up to 12 weeks. The time frame of "Overall" (up to Week 12) represents the median exposure estimate using all available data for each participant in the study.


Enrollment: 183
Study Start Date: February 2011
Study Completion Date: October 2012
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TMC435 100 mg 12 Wks + PR 24/48
Participants received TMC435 100 mg once daily with PegIFNα-2a and ribavirin (PR) for 12 weeks (Wks) followed by PR until Week 24. Treatment was stopped at Week 24 for participants who achieved HCV RNA < 1.2 log10 IU/mL detectable or undetectable at Week 4, and undetectable HCV RNA at Week 12. All other participants continued PR until Week 48.
Drug: TMC435
100-mg capsule taken by mouth once daily for 12 weeks
Drug: Peginterferon alfa-2a (pegIFN alfa-2a)
PegIFN alfa-2a (PEGASYS) will be administered according to the manufacturer's prescribing information as 180 mcg once weekly injected subcutaneous (under the skin) for up to 24-48 weeks for patients randomized to TMC435 and for up to 48 weeks for patients randomized to placebo.
Other Name: PEGASYS
Drug: Ribavirin (RBV)
RBV (COPEGUS) will be administered according to the manufacturer's prescribing information. If body weight is > 80 kg the total daily dose of RBV will be 1000 mg, taken by mouth as 400 mg (2 tablets of 200 mg) after breakfast and 600 mg (3 tablets of 200 mg) after supper. If body weight is > 60 kg to <=80 kg the total daily dose will be 800 mg, taken by mouth as 400 mg (2 tablets of 200 mg per intake) after breakfast and supper. If body weight is <=60 kg the total daily dose of RBV will be 600 mg, taken by mouth as 200 mg (1 tablet of 200 mg) after breakfast and 400 mg (2 tablets of 200 mg) after supper. Total duration of RBV will be 24-48 weeks.
Other Name: COPEGUS
Experimental: PBO 12 Wks + PR 48
Participants received placebo (PBO) once daily with PegIFNα-2a and ribavirin (PR) for 12 weeks (Wks) followed by PR until Week 48.
Drug: Placebo
Placebo capsule taken by mouth once daily for 12 weeks
Drug: Peginterferon alfa-2a (pegIFN alfa-2a)
PegIFN alfa-2a (PEGASYS) will be administered according to the manufacturer's prescribing information as 180 mcg once weekly injected subcutaneous (under the skin) for up to 24-48 weeks for patients randomized to TMC435 and for up to 48 weeks for patients randomized to placebo.
Other Name: PEGASYS
Drug: Ribavirin (RBV)
RBV (COPEGUS) will be administered according to the manufacturer's prescribing information. If body weight is > 80 kg the total daily dose of RBV will be 1000 mg, taken by mouth as 400 mg (2 tablets of 200 mg) after breakfast and 600 mg (3 tablets of 200 mg) after supper. If body weight is > 60 kg to <=80 kg the total daily dose will be 800 mg, taken by mouth as 400 mg (2 tablets of 200 mg per intake) after breakfast and supper. If body weight is <=60 kg the total daily dose of RBV will be 600 mg, taken by mouth as 200 mg (1 tablet of 200 mg) after breakfast and 400 mg (2 tablets of 200 mg) after supper. Total duration of RBV will be 24-48 weeks.
Other Name: COPEGUS

Detailed Description:

This is a randomized (study drug assigned by chance), 2-arm, double-blind study to evaluate the efficacy and safety of TMC435 (also referred to as jnj-38733214-aaa) versus placebo in combination with the standard of care (SoC) therapy (peginterferon alfa-2a [pegIFN alfa-2a] and ribavirin) in adult treatment-naïve patients (who never received treatment for HCV) with chronic genotype 1 HCV infection in Japan. The study objective is to evaluate and compare the efficacy of TMC435 vs placebo by the proportion of the patients with undetectable HCV ribonucleic acid (RNA). In the TMC435 treatment group, patients will receive 12 weeks of treatment with TMC435 (100 mg) once daily plus SoC followed by an additional 12 or 36 weeks of treatment with SoC. In the placebo treatment group, patients will receive 12 weeks of treatment with placebo once daily plus SoC followed by an additional 36 weeks of treatment with SoC. TMC435 is a 100-mg capsule and will be taken orally by mouth. The SoC treatment will be given for 24 or 48 weeks. Pegylated interferon is supplied as a vial containing 1.0 mL solution with 180 mcg pegIFN alpha-2a and administered subcutaneously (injected by a syringe under the skin) once weekly. Ribavirin is given as 200-mg tablets (daily dose: 600-1000 mg based on body weight), and taken orally by mouth two times a day after meals.

  Eligibility

Ages Eligible for Study:   20 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient must have chronic genotype 1 HCV infection with HCV RNA level >= 5.0 log10 IU/mL
  • Patient has never received treatment for HCV
  • Patient must be willing to use contraceptive measures from the time of informed consent to 6 months after last dose of study medication

Exclusion Criteria:

  • Co-infection with any other HCV genotype or co-infection with the human immunodeficiency virus (HIV)
  • Diagnosed with hepatic cirrhosis or hepatic failure
  • A medical condition which is a contraindication to pegIFN or ribavirin therapy
  • History of, or any current medical condition which could impact the safety of the patient in the study
  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: NCT01292239

Locations
Japan
Amagasaki, Japan
Chiba, Japan
Chuo, Japan
Hiroshima, Japan
Ichikawa, Japan
Ikeda, Japan
Inashiki, Japan
Iruma, Japan
Kagoshima, Japan
Kanazawa, Japan
Kitakyushu, Japan
Kumamoto, Japan
Kurume, Japan
Kyoto, Japan
Matsumoto, Japan
Musashino, Japan
Nagoya, Japan
Niigata, Japan
Nishinomiya, Japan
Ohmura, Japan
Osaka, Japan
Osaka-Sayama, Japan
Sakai, Japan
Sapporo, Japan
Sendai, Japan
Tokyo, Japan
Touon, Japan
Yokohama, Japan
Sponsors and Collaborators
Janssen Pharmaceutical K.K.
Investigators
Study Director: Janssen Pharmaceutical K.K. Clinical Trial Janssen Pharmaceutical K.K.
  More Information

No publications provided

Responsible Party: Janssen Pharmaceutical K.K.
ClinicalTrials.gov Identifier: NCT01292239     History of Changes
Other Study ID Numbers: CR017686, TMC435HPC3003
Study First Received: February 1, 2011
Results First Received: October 15, 2013
Last Updated: December 16, 2013
Health Authority: Japan: Japan Pharmaceuticals And Medical Devices Evaluation Center
Japan: Pharmaceuticals and Medical Devices Agency

Keywords provided by Janssen Pharmaceutical K.K.:
Hepatitis C, Chronic
Hepatitis C
Hepatitis C virus
Interferon Alfa-2a
Ribavirin
Viral RNA

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
Interferon-alpha
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 01, 2014