A Study to Assess the Effectiveness, Safety, and Pharmacokinetics of TMC435 in Combination With Peginterferon Alfa-2a and Ribavirin in Hepatitis-C Infected Patients

NCT00996476 | Completed Phase 2 Results

• 2 other identifiers: CR016402TMC435-TiDP16-C215
• Study Type: interventional
• Target: 92
• Locations: 1 country
• Sites: 19

Brief Summary

The purpose of this study is to evaluate effectiveness, safety and pharmacokinetics (Explores what the body does to the medication) of TMC435350 in combination with Peginterferon Alfa-2a and Ribavirin in genotype 1 hepatitis C virus infected Japanese participants who have never received treatment for their hepatitis C infection.

Conditions

Hepatitis C, Chronic

Keywords

Hepatitis C; Hepatitis C virus; Interferon Alfa-2a; Ribavirin; Viral RNA

Outcome Measures

Primary Outcomes (14)

• Change in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels From Baseline to Week 4

  The table below shows the least-squares (LS) mean change and 95% confidence intervals (CI) change from baseline at Week 4 in HCV RNA levels for participants in the 2 TMC435 50 mg treatment groups combined (TMC12/PR24 50 mg and TMC24/PR24 50 mg) and for participants in the 2 TMC435 100 mg treatment groups combined (TMC12/PR24 100 mg and TMC24/PR24 100 mg). The statistical analyses show the difference in LS mean change from baseline from the PR48 control group and the 95% CI for each dose group (ie, each TMC435 dose group minus PR48 control). NOTE: All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated (refer to Limits and Caveats).

  Day 1 (Baseline) and Week 4

• The Percentage of Participants With Undetectable Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels During the Study

  The table below shows the percentage of participants in each treatment group with undetectable plasma HCV RNA levels at Weeks 4, 12, 24, 48, and end of treatment (EOT, up to Week 24 or 48). The number of participants analyzed is listed at each time point in order of the treatment groups from left to right in the table (ie, Week x, n=x, x, x, x, and x) if different from the "Number of Participants Analyzed."NOTE: All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated (refer to Limits and Caveats).

  Weeks 4, 12, 24 or 48, and EOT (up to Week 24 or 48)

• The Percentage of Participants With a Decrease of Greater Than or Equal to 2 log10 IU/mL From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Through the Post-treatment Follow-up Period

  The table below shows the percentage of participants in each treatment group with a decrease of greater than (\>) or equal (=) to 2 log10 IU/mL from baseline in plasma HCV RNA levels at time points during the treatment period and post treatment follow-up period. The number of participants analyzed is listed at each time point in order of the treatment groups from left to right in the table (ie, Week x, n=x, x, x, x, and x) if different from the "Number of Participants Analyzed." NOTE: All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated (refer to Limits and Caveats).

  Days 1 (4 hr), 1 (8 hr), 3, Weeks 1, 2, 3, 4, 6, 8, 12, 16, 20, 24,28, 36, 42, 48, 52, 60, 72, and EOT (up to Week 24 or 48)

• The Percentage of Participants With Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels Undetectable or Below the Limit of Quantification (<1.2 log10 IU/mL Detectable) During Treatment and During Post Treatment Follow-up

  The table below shows the percentage of participants in each treatment group with plasma HCV RNA levels undetectable or below the limit of quantification (\<1.2 log10 IU/mL detectable ) at time points during treatment and post treatment follow-up.The number of participants analyzed is listed at each time point in order of the treatment groups from left to right in the table (ie, Week x, n=x, x, x, x, and x) if different from the "Number of Participants Analyzed." NOTE: All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated (refer to Limits and Caveats).

  Week 4, 12, 24, 36, 48, EOT (up to Week 24 or 48), and Week 60 and 72

• The Number of Participants With Viral Breakthrough

  The table below shows the number of participants in each treatment group who experienced viral breakthrough during the 48 week treatment period with at least one study medication (TMC435 or PegIFNα-2a and ribavirin). Viral breakthrough is defined as a confirmed increase of greater than (\>) 1 log10 IU/mL in plasma hepatitis C virus (HCV) ribonucleic acid (RNA) level 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 reported below 1.2 log10 IU/mL detectable or undetectable during the treatment period. The number of participants analyzed is listed at each time point in order of the treatment groups from left to right in the table (ie, Week x, n=x, x, x, x, and x) if different from the "Number of Participants Analyzed." NOTE: All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated (refer to Limits and Caveats).

  Up to EOT (up to Week 24 or 48)

• The Percentage of Participants With Viral Relapse

  The table below shows the percentage of participants in each treatment group who experienced viral relapse within 12 weeks (ie, at Week 36 or 60) after actual end of treatment (EOT) (up to Week 24 or 48). Viral relapse was defined as confirmed detectable plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels during the post treatment follow-up period at Weeks 36 or 60 in participants with undetectable plasma HCV RNA at EOT. The statistical analysis shows the difference in treatments (ie, each TMC435 group minus PR48 control) in viral relapse. NOTE: All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated (refer to Limits and Caveats).

  Week 36 or 60

• Actual Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Values up to Week 24 in the Post-treatment Follow-up Period

  The table below shows the mean (standard deviation) of the actual HCV RNA values by treatment group at Baseline and Weeks 4, 12, 24, 48, end of treatment (EOT, up to Weeks 24 or 48), Weeks 60 and 72 (Week 24 in the post-treatment follow-up period). The number of participants analyzed is listed at each time point in order of the treatment groups from left to right in the table (ie, Week x, n=x, x, x, x, and x) if different from the "Number of Participants Analyzed." NOTE: All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated (refer to Limits and Caveats).

  Baseline, Week 4, 12, 24, 48, EOT (up to Week 24 or 48), and Weeks 60 and 72

• The Number of Participants With Alanine Aminotransaminase (ALT) Values Within the Normal Range at the End-of-treatment (EOT)

  The table below shows the number of participants whose ALT results were within the normal range on Day 1 (initial day of treatment), Week 24, 48, and EOT (up to Weeks 24 or 48).The number of participants analyzed is listed at each time point in order of the treatment groups from left to right in the table (ie, Week x, n=x, x, x, x, and x) if different from the "Number of Participants Analyzed." NOTE: All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated (refer to Limits and Caveats).

  Day 1, Weeks 24, 48, and EOT (up to Weeks 24 or 48)

• The Percentage of Participants With Sustained Virologic Response (SVR)

  The table below shows the percentage of participants with a SVR4, SVR12, and SVR24 defined as undetectable plasma hepatitis C virus (HCV) ribonucleic acid (RNA) at the end of treatment (EOT) (up to Weeks 24 or 48) and at 4, 12, and 24 weeks, respectively, after the last dose of treatment. NOTE: All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated (refer to Limits and Caveats).

  SVR4 (up to Week 28 or Week 52), SVR12 (up to Weeks 36 or 60), and SVR24 (up to Weeks 48 or 72)

• Predose Plasma Concentrations (C0h) of TMC435 (Sparse Blood Sampling)

  The table below shows the mean (standard deviation) predose plasma concentration (C0h) for participants in each treatment group at Weeks 4, 12, and 24. The number of participants analyzed is listed at each time point in order of the treatment groups from left to right in the table (ie, Week x, n=x, x, x, x, and x) if different from the "Number of Participants Analyzed." NOTE: All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated (refer to Limits and Caveats).

  Weeks 4, 12, and 24

• Predose Plasma Concentrations (C0h) of TMC435 (Intensive Blood Sampling)

  The table below shows the mean predose plasma concentration (C0h) for participants in the 2 TMC435 50 mg treatment groups combined and for participants in the 2 TMC435 100 mg treatment groups combined who had intensive blood samples collected at Weeks 4 to 6. NOTE: All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated (refer to Limits and Caveats).

  Weeks 4 to 6

• The Area Under the Plasma Concentration-time Curve From the Time of Administration up to 24 Hours After Dosing (AUC24) for TMC435

  The table below shows the mean AUC24 of TMC435 for participants in the 2 TMC435 50 mg treatment groups combined (TMC12/PR24 50 mg and TMC24/PR24 50 mg) and for participants in the 2 TMC435 100 mg treatment groups combined (TMC12/PR24 100 mg and TMC24/PR24 100 mg) who had intensive blood samples collected at Weeks 4 to 6. NOTE: All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated (refer to Limits and Caveats).

  within 15 minutes and at 1, 2, 4, 6, 8, 12, and 24 hours post-dose between Week 4 and Week 6 after the initiation of treatment

• Time to Reach the Maximum Plasma Concentration (Tmax) of TMC435

  The table below shows the median time in hours to reach the maximum plasma concentration (tmax) of TMC435 for participants in the 2 TMC435 50 mg treatment groups combined (TMC12/PR24 50 mg and TMC24/PR24 50 mg) and for participants in the 2 TMC435 100 mg treatment groups combined (TMC12/PR24 100 mg and TMC24/PR24 100 mg) who had intensive blood samples collected at Weeks 4 to 6. NOTE: All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated (refer to Limits and Caveats).

  within 15 minutes and at 1, 2, 4, 6, 8, 12, and 24 hours post-dose between Week 4 and Week 6 after the initiation of treatment

• The Number of Participants Who Met Virologic Stopping/Continuation Rules and Completed All Study Medications

  The table below shows the number of participants who met response-guided treatment (RGT) stopping criteria in the TMC435 treatment groups. Participants who achieved plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels less than 1.4 log10 IU/mL at Week 4 and had undetectable plasma HCV RNA at Weeks 12, 16 and 20 were to stop all study medication (TMC435, PegIFNα-2a, and ribavirin) at Week 24. All other participants continued PegIFNα-2a and ribavirin until Week 48. NOTE: All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated (refer to Limits and Caveats).

  Week 24

Study Arms (5)

TMC12/PR24 50 mg

EXPERIMENTAL

Participants received TMC435 50 mg once daily with PegIFNa-2a and ribavirin (PR) for 12 weeks followed by PR until Week 24 Participants who achieved plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels \<1.4 log10 IU/mL at Week 4 and had undetectable plasma HCV RNA at Weeks 12, 16 and 20, discontinued all study treatment (TMC435 and PR) at Week 24. All other participants continued PR until Week 48.

Drug: TMC435; Drug: PegIFNα-2a; Drug: RBV

TMC12/PR24 100 mg

EXPERIMENTAL

Participants received TMC435 100 mg once daily plus PegIFNa-2a and ribavirin (PR) for 12 weeks followed by PR until Week 24. Participants who achieved plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels \<1.4 log10 IU/mL at Week 4 and had undetectable plasma HCV RNA at Weeks 12, 16 and 20, discontinued all study treatment (TMC435 and PR) at Week 24. All other participants continued PR until Week 48.

Drug: TMC435; Drug: PegIFNα-2a; Drug: RBV

TMC24/PR24 50 mg

EXPERIMENTAL

Participants received TMC435 50 mg once daily plus PegIFNa-2a and ribavirin (PR) for 24 weeks. Participants who achieved plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels \<1.4 log10 IU/mL at Week 4 and had undetectable plasma HCV RNA at Weeks 12, 16 and 20, discontinued all study treatment (TMC435, PR) at Week 24. All other participants continued PR until Week 48.

Drug: TMC435; Drug: PegIFNα-2a; Drug: RBV

TMC24/PR24 100 mg

EXPERIMENTAL

Participants received TMC435 100 mg once daily plus PegIFNa-2a and ribavirin (PR) for 24 weeks. Participants who achieved plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels \<1.4 log10 IU/mL at Week 4 and had undetectable plasma HCV RNA at Weeks 12, 16 and 20, discontinued all study treatment (TMC435 and PR) at Week 24. All other participants continued PR until Week 48.

Drug: TMC435; Drug: PegIFNα-2a; Drug: RBV

PR48 Control

EXPERIMENTAL

Participants received PegIFNa-2a and ribavirin (PR) for 48 weeks (PR48 control group)

Drug: TMC435; Drug: PegIFNα-2a; Drug: RBV

Interventions

TMC435 DRUG

One 50 or 100-mg capsule orally (by mouth), once daily for 12 or 24 weeks

PR48 Control; TMC12/PR24 100 mg; TMC12/PR24 50 mg; TMC24/PR24 100 mg; TMC24/PR24 50 mg

PegIFNα-2a DRUG

One subcutaneous injection of PegIFNα-2a 180 μg once weekly for 12, 24, or 48 weeks.

PR48 Control; TMC12/PR24 100 mg; TMC12/PR24 50 mg; TMC24/PR24 100 mg; TMC24/PR24 50 mg

RBV DRUG

300, 400, or 500-mg tablets orally twice daily for 12, 24, or 48 weeks.

PR48 Control; TMC12/PR24 100 mg; TMC12/PR24 50 mg; TMC24/PR24 100 mg; TMC24/PR24 50 mg

Eligibility Criteria

• Age: 20 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants with documented chronic hepatitis C infection as evidenced by presence of HCV antibody at least 6 months (180 days) prior to the informed consent. - Participants with genotype 1 HCV infection. - Participants with plasma HCV RNA level of ≥ 5.0 log10 IU/mL at screening.

You may not qualify if:

• Participants diagnosed with hepatic cirrhosis or hepatic failure. - Participants with any other liver disease than hepatitis C. - Participants with infection/co-infection with non-genotype 1 HCV.

Sponsors & Collaborators

• Janssen Pharmaceutical K.K.: lead

Study Sites (19)

Unknown Facility

Amagasaki, Japan

Location

Unknown Facility

Hiroshima, Japan

Location

Unknown Facility

Kagoshima, Japan

Location

Unknown Facility

Kawasaki, Japan

Location

Unknown Facility

Kitakyushu, Japan

Location

Unknown Facility

Kurume, Japan

Location

Unknown Facility

Kyoto, Japan

Location

Unknown Facility

Matsumoto, Japan

Location

Unknown Facility

Musashino, Japan

Location

Unknown Facility

Nishinomiya, Japan

Location

Unknown Facility

Ohmura, Japan

Location

Unknown Facility

Osaka, Japan

Location

Unknown Facility

Ōsaka-sayama, Japan

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Unknown Facility

Sakai, Japan

Location

Unknown Facility

Sapporo, Japan

Location

Unknown Facility

Suita, Japan

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Unknown Facility

Tokyo, Japan

Location

Unknown Facility

Touon, Japan

Location

Unknown Facility

Yokohama, Japan

Location

Related Publications (1)

• Hayashi N, Seto C, Kato M, Komada Y, Goto S. Once-daily simeprevir (TMC435) with peginterferon/ribavirin for treatment-naive hepatitis C genotype 1-infected patients in Japan: the DRAGON study. J Gastroenterol. 2014 Jan;49(1):138-47. doi: 10.1007/s00535-013-0875-1. Epub 2013 Sep 5.

  PMID: 24005956 DERIVED

MeSH Terms

Conditions

Hepatitis C, Chronic; Hepatitis C

Interventions

Simeprevir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sulfonamides; Sulfones; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated. "Primary" was chosen for each outcome measure because "Exploratory" is not available as an outcome measure type.

Results Point of Contact

• Title: DIrector
• Organization: Janssen Pharmaceutical K.K., Japan

81 3 44115639

Study Officials

• Janssen Pharmaceutical K.K. Clinical Trial

  Janssen Pharmaceutical K.K.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 15, 2009
• First Posted: October 16, 2009
• Study Start: July 1, 2009
• Primary Completion: January 1, 2011
• Study Completion: January 1, 2011
• Last Updated: April 17, 2014
• Results First Posted: April 17, 2014

Record last verified: 2014-03

Locations

JP (19)