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CompletedNCT00882908PILLARUpdated Jun 16, 2014Results posted

A Study of TMC435 in Combination With Pegylated Interferon Alp\Fa-2a and Ribavirin in Patients Infected With Genotype 1 Hepatitis C Virus Who Never Received Treatment

A Phase 2 interventional study of TMC435 and Ribavirin (R) in Hepatitis C, sponsored by Tibotec Pharmaceuticals, Ireland. Completed at 73 sites in 13 countries. Open to participants aged 18 Years to 70 Years. Per ClinicalTrials.gov, last updated 2014-06-16.

Sponsored by Tibotec Pharmaceuticals, Ireland · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
386
Allocation
Randomized
Ages
18 Years to 70 Years
Sex
All
01

Study summary

The purpose of this study is to evaluate the efficacy of 4 different regimens of TMC435 in combination with peginterferon alfa-2a (PegIFNα-2a) and ribavirin (RBV), defined as the proportion of patients with sustained virologic response at Week 72 (patients with undetectable plasma HCV RNA [less than 25 IU per mL undetectable] at the end of treatment and at Week 72), compared to the control group receiving PegIFN and RBV in combination with TMC435-matched placebo.

Read the detailed description

This is a randomized (study medication assigned by chance), 5-arm, double-blind (neither investigator nor the participant knows the treatment that the participant receives), placebo-controlled (an inactive substance that is compared with the study medication to test whether the study medication has a real effect in clinical study) study to compare the efficacy, tolerability and safety of different TMC435 regimens combined with peginterferon alfa-2a (PegIFNα-2a) and ribavirin (RBV) versus PegIFNα-2a plus RBV alone in adult treatment-naive patients with chronic genotype 1 HCV infection. The study mainly consists of 3 phases: screening phase (approximately 6 weeks), treatment phase (up to 48 weeks), and follow up phase (up to 48 weeks). In the treatment phase, patients will be divided in to 5 different arms in a 1:1:1:1:1 randomized ratio. In treatment arms 1 and 2, patients will receive 12 weeks of therapy with TMC435 along with PegIFNα 2a and RBV followed by treatment with PegIFNα 2a, RBV, and TMC435-matched placebo. In treatment arms 3 and 4, patients will receive 24 weeks of therapy with TMC435, PegIFNα 2a, and RBV. In treatment arm 5 (control group), patients will receive PegIFNα 2a and RBV for 48 weeks and TMC435 matched placebo for the first 24 weeks. Collection of blood samples for efficacy evaluations will be done at scheduled visits throughout the study. Safety evaluations for adverse events, clinical laboratory tests, physical examination, vital signs and electrocardiogram will be monitored throughout the study. The total duration of the study will be up to approximately 72 weeks after initiation of treatment.

02

Conditions studied

  • Hepatitis C

Keywords

  • Hepatitis C
  • TMC435
  • Peginterferon alpha-2a
  • PegIFNalpha-2a
  • RBV
  • Ribavirin
  • Placebo
03

In context

Hepatitis A

2,709 studies on the registry are indexed under Hepatitis A; 142 are open to participants now.

This study's enrollment of 386 is above the median of 100 across 1,886 interventional studies indexed under Hepatitis A.

Browse Hepatitis A studies →

Lead sponsor

Tibotec Pharmaceuticals, Ireland is the lead sponsor of 75 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 70 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Patients with documented chronic genotype-1 hepatitis C infection and with plasma HCV RNA of > 100,000 IU/mL at screening
  • Patients that have not been treated before for HCV
  • Patients that are of childbearing potential or have a partner of childbearing potential should agree to use 2 effective methods of contraception

Exclusion criteria

Exclusion Criteria:

  • Patients with cirrhosis or evidence of hepatic decompensation
  • Co-infection with the human immunodeficiency virus (HIV)
  • Any contraindication to Pegasys or Copegus therapy
  • History of, or any current medical condition which could impact the safety of the patient in the study
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
386 participants (actual)

Study arms

  • Experimental
    TMC435 75 mg 12 Wks + PR 24/48

    Participants will receive TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo once daily and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.

    Drug: TMC435 · Drug: Ribavirin (R) · Drug: PegIFNα-2a (P) · Drug: Placebo

  • Experimental
    TMC435 75 mg 24 Wks + PR 24/48

    Participants will receive TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.

    Drug: TMC435 · Drug: Ribavirin (R) · Drug: PegIFNα-2a (P) · Drug: Placebo

  • Experimental
    TMC435 150 mg 12 Wks + PR 24/48

    Participants will receive TMC435 150 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed Placebo and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.

    Drug: TMC435 · Drug: Ribavirin (R) · Drug: PegIFNα-2a (P) · Drug: Placebo

  • Experimental
    TMC435 150 mg 24 Wks + PR 24/48

    Participants will receive TMC435 150 mg once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.

    Drug: TMC435 · Drug: Ribavirin (R) · Drug: PegIFNα-2a (P) · Drug: Placebo

  • Placebo comparator
    Placebo 24 Wks + PR48

    Participants will receive Placebo once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks followed by PR until Week 48.

    Drug: Ribavirin (R) · Drug: PegIFNα-2a (P) · Drug: Placebo

Interventions

  • DrugTMC435

    TMC435 will be administered as one or two 75 mg capsules orally, once daily, for 12 or 24 weeks.

    Also known as: TMC 435

  • DrugRibavirin (R)

    Ribavirin (R) will be administered as 200 mg tablets (5 to 6 tablets) orally, twice daily, for 48 weeks.

    Also known as: COPEGUS

  • DrugPegIFNα-2a (P)

    PegIFNα-2a (P) 180 micrograms will be administered as a subcutaneous (under the skin) injection, once weekly for 48 weeks.

    Also known as: PEGASYS

  • DrugPlacebo

    Placebo capsules identical in appearance to TMC435 capsule will be administered orally, once daily, for 48 weeks.

06

What researchers measure

Primary outcomes

  1. The Percentage of Participants Achieving a Sustained Virologic Response at Week 72 (SVRW72)

    The table below shows the percentage of participants in each treatment group who achieved a SVRW72, defined as the percentage of participants with undetectable plasma Hepatitis C virus ribonucleic acid levels at end of treatment (EOT) and at Week 72.

    Time frame: Week 72

Secondary outcomes

  1. The Percentage of Participants Achieving Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels of Less Than 25 IU/mL Undetectable During Treatment and Follow-up

    The table below shows the percentage of participants in each treatment group who achieved plasma HCV RNA levels of less than 25 IU/mL undetectable at selected time points during treatment, follow-up, and at end of treatment (EOT).

    Time frame: Weeks, 2, 4, 8, 12, 24, 36, 48, 60, 72, and at EOT (up to Week 24 or 48)

  2. The Percentage of Participants Who Achieved Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels of Less Than 25 IU/mL Detectable or Undetectable During Treatment and Follow-up

    The table below shows the percentage of participants in each treatment group who achieved plasma levels of HCV RNA less than 25 IU/mL detectable or undetectable at selected time points during treatment, follow-up, and at end of treatment (EOT).

    Time frame: Weeks 2, 4, 8, 12, 24, 36, 48, 60, 72, and at EOT (up to Week 24 or 48)

  3. The Percentage of Participants Achieving Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels of Greater Than or Equal to 2 log10 Drop During Treatment

    The table below shows the percentage of participants in each treatment group who achieved plasma levels of HCV RNA greater than or equal to 2 log10 drop from Baseline at selected time points during treatment.

    Time frame: Baseline (Day 1) and Weeks, 2, 4, 8, and 12

  4. The Percentage of Participants Who Achieved a Sustained Virologic Response 24 Weeks After the Planned End of Treatment (SVR24)

    The table below shows the percentage of participants in each treatment group who achieved a SVR24, defined as having undetectable plasma Hepatitis C virus ribonucleic acid levels at the end of treatment (EOT) and 24 weeks after the EOT.

    Time frame: Week 48 or 72

  5. The Percentage of Participants Achieving a Rapid Virologic Response (RVR)

    The table below shows the percentage of participants in each treatment group who achieved a RVR, defined as having undetectable plasma Hepatitis C virus ribonucleic acid levels after receiving 4 weeks of treatment.

    Time frame: Week 4

  6. The Percentage of Participants Achieving an Early Virologic Response (EVR)

    The table below shows the percentage of participants who achieved an EVR, defined as having a change from baseline in plasma Hepatitis C virus ribonucleic acid of 2 log10 at Week 12.

    Time frame: Baseline (Day 1) and Week 12

  7. The Percentage of Participants Achieving a Complete Early Virologic Response (cEVR)

    The table below shows the percentage of participants in each treatment group who had a cEVR, defined as having undetectable plasma Hepatitis C Virus ribonucleic acid levels at Week 12.

    Time frame: Week 12

  8. The Percentage of Participants Achieving a Sustained Virologic Response 12 Weeks After the Planned End of Treatment (SVR12)

    The table below shows the percentage of participants who achieved undetectable plasma Hepatitis C virus ribonucleic acid levels at the end of treatment (EOT) and 12 Weeks after the EOT.

    Time frame: Up to Week 36 or 52

  9. Number of Participants With Viral Breakthrough

    The table below shows the number of participants in each treatment group who experienced viral breakthrough during the TMC435 treatment period of the study, defined as a confirmed increase of more 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 more than 100 IU/mL in participants whose plasma HCV RNA level had previously been below the limit of quantification (less than 25 IU/mL detectable or undetectable).

    Time frame: Week 24 or 48

  10. The Number of Participants With Viral Relapse

    The table below shows the number of participants who experienced viral relapse, defined as a confirmed detectable plasma Hepatitis C virus (HCV) ribonucleic acid (RNA) level during the follow-up period in participants with undetectable plasma HCV RNA (less than 25 IU/mL undetectable) at the end of treatment.

    Time frame: Up to Week 72

  11. The Number of Participants With Abnormal Alanine Aminotransferase (ALT) Levels at Baseline Who Achieved Normalized ALT Levels at the End of Treatment (EOT)

    The table below shows the number of participants with abnormal ALT levels at Baseline who achieved ALT levels within the normal range at the EOT.

    Time frame: Baseline (Day 1) up to Week 24 or 48

  12. Plasma Concentrations of TMC435

    The table below shows median (range) predose plasma concentration (C0h) values and median (range) average steady-state plasma concentration (Css,av) values for participants in each of the 4 TMC435 treatment groups.

    Time frame: Two random blood samples taken at least 2 hours apart at Weeks 2, 4, 8, 12, 16, and 24

  13. Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC24h) for TMC435

    The table below shows the median (range) AUC24h values for TMC435 for participants in each of the 4 TMC435 treatment groups. Two blood samples taken at least 2 hours apart from each other for determination of TMC435 plasma pharmacokinetics were obtained in all participants on Weeks 2, 4, 8, 12, 16, and 24 to obtain Bayesian estimates of TMC435 AUC24h (overall exposure).

    Time frame: Two random blood samples taken at least 2 hours apart at Weeks 2, 4, 8, 12, 16, and 24

07

Results

Posted Jun 16, 2014

Participant flow

The study was conducted at 79 sites in 13 countries: Australia, New Zealand, Canada, Austria, Belgium, Germany, Spain, France, Poland, Russia, Norway, Denmark, and the United States. Approximately 68% of participants were enrolled in Europe, 21% in North America, and 11% in Australia/New Zealand.

Participant flow — Overall Study
MilestoneTMC435 75 mg 12 Wks + PR 24/48TMC435 75 mg 24 Wks + PR 24/48TMC435 150 mg 12 Wks + PR 24/48TMC435 150 mg 24 Wks + PR 24/48Placebo 24 Wks + PR48
Started7875777977
Completed7569707271
Not completed36776
Withdrew: Adverse event00101
Withdrew: Lost to follow-up35312
Withdrew: Protocol violation01000
Withdrew: Withdrawal by subject00352
Withdrew: Subject reached a virologic endpoint00001
Withdrew: Study terminated in error00010

Outcome measures

PrimaryThe Percentage of Participants Achieving a Sustained Virologic Response at Week 72 (SVRW72)

The table below shows the percentage of participants in each treatment group who achieved a SVRW72, defined as the percentage of participants with undetectable plasma Hepatitis C virus ribonucleic acid levels at end of treatment (EOT) and at Week 72.

Time frame:
Week 72
Reported as:
Number · Percentage of participants
The Percentage of Participants Achieving a Sustained Virologic Response at Week 72 (SVRW72)
Percentage of participantsTMC435 75 mg 12 Wks + PR 24/48TMC435 75 mg 24 Wks + PR 24/48TMC435 150 mg 12 Wks + PR 24/48TMC435 150 mg 24 Wks + PR 24/48Placebo 24 Wks + PR48
The Percentage of Participants Achieving a Sustained Virologic Response at Week 72 (SVRW72)80.870.777.984.864.9
Statistical analysis
  • TMC435 75 mg 12 Wks + PR 24/48 vs TMC435 75 mg 24 Wks + PR 24/48 vs Placebo 24 Wks + PR48 · Regression, Logistic · p = 0.051 · Difference in proportions of svrw72: 13.0 · 97.5% CI -1.9 to 28.0Difference in percentages of participants in the TMC435 75mg and placebo groups with undetectable plasma Hepatitis C virus ribonucleic acid levels at end of treatment (EOT) and at Week 72 estimated from the logistic regression model.
  • TMC435 150 mg 12 Wks + PR 24/48 vs TMC435 150 mg 24 Wks + PR 24/48 vs Placebo 24 Wks + PR48 · Regression, Logistic · p = 0.004 · Difference in proportions of svrw72: 18.9 · 97.5% CI 4.4 to 33.5Difference in percentages of participants in the TMC435 150mg and placebo groups with undetectable plasma Hepatitis C virus ribonucleic acid levels at end of treatment (EOT) and at Week 72 estimated from the logistic regression model.
SecondaryThe Percentage of Participants Achieving Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels of Less Than 25 IU/mL Undetectable During Treatment and Follow-up

The table below shows the percentage of participants in each treatment group who achieved plasma HCV RNA levels of less than 25 IU/mL undetectable at selected time points during treatment, follow-up, and at end of treatment (EOT).

Time frame:
Weeks, 2, 4, 8, 12, 24, 36, 48, 60, 72, and at EOT (up to Week 24 or 48)
Reported as:
Number · Percentage of participants
The Percentage of Participants Achieving Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels of Less Than 25 IU/mL Undetectable During Treatment and Follow-up
Percentage of participantsTMC435 75 mg 12 Wks + PR 24/48TMC435 75 mg 24 Wks + PR 24/48TMC435 150 mg 12 Wks + PR 24/48TMC435 150 mg 24 Wks + PR 24/48Placebo 24 Wks + PR48
Week 239.730.723.439.22.6
Week 475.668.075.374.75.2
Week 887.290.792.293.726.0
Week 1291.093.393.594.955.8
Week 2492.393.384.487.377.9
Week 3685.981.381.884.876.6
Week 4879.577.379.282.374.0
Week 6079.568.075.383.563.6
Week 7279.570.777.982.364.9
EOT (up to Week 24 or 48)92.397.392.293.779.2
SecondaryThe Percentage of Participants Who Achieved Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels of Less Than 25 IU/mL Detectable or Undetectable During Treatment and Follow-up

The table below shows the percentage of participants in each treatment group who achieved plasma levels of HCV RNA less than 25 IU/mL detectable or undetectable at selected time points during treatment, follow-up, and at end of treatment (EOT).

Time frame:
Weeks 2, 4, 8, 12, 24, 36, 48, 60, 72, and at EOT (up to Week 24 or 48)
Reported as:
Number · Percentage of participants
The Percentage of Participants Who Achieved Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels of Less Than 25 IU/mL Detectable or Undetectable During Treatment and Follow-up
Percentage of participantsTMC435 75 mg 12 Wks + PR 24/48TMC435 75 mg 24 Wks + PR 24/48TMC435 150 mg 12 Wks + PR 24/48TMC435 150 mg 24 Wks + PR 24/48Placebo 24 Wks + PR48
Week 265.466.775.378.55.2
Week 485.988.090.991.115.6
Week 893.694.793.593.749.4
Week 1293.694.796.194.966.2
Week 2492.393.384.489.980.5
Week 3685.981.381.884.879.2
Week 4879.577.379.282.375.3
Week 6079.568.075.383.564.9
Week 7279.570.777.983.564.9
EOT (up to Week 24 or 48)93.697.392.296.283.1
SecondaryThe Percentage of Participants Achieving Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels of Greater Than or Equal to 2 log10 Drop During Treatment

The table below shows the percentage of participants in each treatment group who achieved plasma levels of HCV RNA greater than or equal to 2 log10 drop from Baseline at selected time points during treatment.

Time frame:
Baseline (Day 1) and Weeks, 2, 4, 8, and 12
Reported as:
Number · Percentage of participants
The Percentage of Participants Achieving Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels of Greater Than or Equal to 2 log10 Drop During Treatment
Percentage of participantsTMC435 75 mg 12 Wks + PR 24/48TMC435 75 mg 24 Wks + PR 24/48TMC435 150 mg 12 Wks + PR 24/48TMC435 150 mg 24 Wks + PR 24/48Placebo 24 Wks + PR48
Week 293.698.797.498.740.3
Week 494.998.797.493.771.4
Week 897.497.397.494.984.4
Week 1297.496.096.196.289.6
SecondaryThe Percentage of Participants Who Achieved a Sustained Virologic Response 24 Weeks After the Planned End of Treatment (SVR24)

The table below shows the percentage of participants in each treatment group who achieved a SVR24, defined as having undetectable plasma Hepatitis C virus ribonucleic acid levels at the end of treatment (EOT) and 24 weeks after the EOT.

Time frame:
Week 48 or 72
Reported as:
Number · Percentage of participants
The Percentage of Participants Who Achieved a Sustained Virologic Response 24 Weeks After the Planned End of Treatment (SVR24)
Percentage of participantsTMC435 75 mg 12 Wks + PR 24/48TMC435 75 mg 24 Wks + PR 24/48TMC435 150 mg 12 Wks + PR 24/48TMC435 150 mg 24 Wks + PR 24/48Placebo 24 Wks + PR48
The Percentage of Participants Who Achieved a Sustained Virologic Response 24 Weeks After the Planned End of Treatment (SVR24)82.174.780.586.164.9
SecondaryThe Percentage of Participants Achieving a Rapid Virologic Response (RVR)

The table below shows the percentage of participants in each treatment group who achieved a RVR, defined as having undetectable plasma Hepatitis C virus ribonucleic acid levels after receiving 4 weeks of treatment.

Time frame:
Week 4
Reported as:
Number · Percentage of participants
The Percentage of Participants Achieving a Rapid Virologic Response (RVR)
Percentage of participantsTMC435 75 mg 12 Wks + PR 24/48TMC435 75 mg 24 Wks + PR 24/48TMC435 150 mg 12 Wks + PR 24/48TMC435 150 mg 24 Wks + PR 24/48Placebo 24 Wks + PR48
The Percentage of Participants Achieving a Rapid Virologic Response (RVR)75.668.075.374.75.2
SecondaryThe Percentage of Participants Achieving an Early Virologic Response (EVR)

The table below shows the percentage of participants who achieved an EVR, defined as having a change from baseline in plasma Hepatitis C virus ribonucleic acid of 2 log10 at Week 12.

Time frame:
Baseline (Day 1) and Week 12
Reported as:
Number · Percentage of participants
The Percentage of Participants Achieving an Early Virologic Response (EVR)
Percentage of participantsTMC435 75 mg 12 Wks + PR 24/48TMC435 75 mg 24 Wks + PR 24/48TMC435 150 mg 12 Wks + PR 24/48TMC435 150 mg 24 Wks + PR 24/48Placebo 24 Wks + PR48
The Percentage of Participants Achieving an Early Virologic Response (EVR)97.496.096.196.289.6
SecondaryThe Percentage of Participants Achieving a Complete Early Virologic Response (cEVR)

The table below shows the percentage of participants in each treatment group who had a cEVR, defined as having undetectable plasma Hepatitis C Virus ribonucleic acid levels at Week 12.

Time frame:
Week 12
Reported as:
Number · Percentage of participants
The Percentage of Participants Achieving a Complete Early Virologic Response (cEVR)
Percentage of participantsTMC435 75 mg 12 Wks + PR 24/48TMC435 75 mg 24 Wks + PR 24/48TMC435 150 mg 12 Wks + PR 24/48TMC435 150 mg 24 Wks + PR 24/48Placebo 24 Wks + PR48
The Percentage of Participants Achieving a Complete Early Virologic Response (cEVR)91.093.393.594.955.8
SecondaryThe Percentage of Participants Achieving a Sustained Virologic Response 12 Weeks After the Planned End of Treatment (SVR12)

The table below shows the percentage of participants who achieved undetectable plasma Hepatitis C virus ribonucleic acid levels at the end of treatment (EOT) and 12 Weeks after the EOT.

Time frame:
Up to Week 36 or 52
Reported as:
Number · Percentage of participants
The Percentage of Participants Achieving a Sustained Virologic Response 12 Weeks After the Planned End of Treatment (SVR12)
Percentage of participantsTMC435 75 mg 12 Wks + PR 24/48TMC435 75 mg 24 Wks + PR 24/48TMC435 150 mg 12 Wks + PR 24/48TMC435 150 mg 24 Wks + PR 24/48Placebo 24 Wks + PR48
The Percentage of Participants Achieving a Sustained Virologic Response 12 Weeks After the Planned End of Treatment (SVR12)83.376.080.586.166.2
SecondaryNumber of Participants With Viral Breakthrough

The table below shows the number of participants in each treatment group who experienced viral breakthrough during the TMC435 treatment period of the study, defined as a confirmed increase of more 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 more than 100 IU/mL in participants whose plasma HCV RNA level had previously been below the limit of quantification (less than 25 IU/mL detectable or undetectable).

Time frame:
Week 24 or 48
Reported as:
Number · Participants
Number of Participants With Viral Breakthrough
ParticipantsTMC435 75 mg 12 Wks + PR 24/48TMC435 75 mg 24 Wks + PR 24/48TMC435 150 mg 12 Wks + PR 24/48TMC435 150 mg 24 Wks + PR 24/48Placebo 24 Wks + PR48
Number of Participants With Viral Breakthrough52624
SecondaryThe Number of Participants With Viral Relapse

The table below shows the number of participants who experienced viral relapse, defined as a confirmed detectable plasma Hepatitis C virus (HCV) ribonucleic acid (RNA) level during the follow-up period in participants with undetectable plasma HCV RNA (less than 25 IU/mL undetectable) at the end of treatment.

Time frame:
Up to Week 72
Reported as:
Number · Participants
The Number of Participants With Viral Relapse
ParticipantsTMC435 75 mg 12 Wks + PR 24/48TMC435 75 mg 24 Wks + PR 24/48TMC435 150 mg 12 Wks + PR 24/48TMC435 150 mg 24 Wks + PR 24/48Placebo 24 Wks + PR48
The Number of Participants With Viral Relapse8146611
SecondaryThe Number of Participants With Abnormal Alanine Aminotransferase (ALT) Levels at Baseline Who Achieved Normalized ALT Levels at the End of Treatment (EOT)

The table below shows the number of participants with abnormal ALT levels at Baseline who achieved ALT levels within the normal range at the EOT.

Time frame:
Baseline (Day 1) up to Week 24 or 48
Reported as:
Number · Participants
The Number of Participants With Abnormal Alanine Aminotransferase (ALT) Levels at Baseline Who Achieved Normalized ALT Levels at the End of Treatment (EOT)
ParticipantsTMC435 75 mg 12 Wks + PR 24/48TMC435 75 mg 24 Wks + PR 24/48TMC435 150 mg 12 Wks + PR 24/48TMC435 150 mg 24 Wks + PR 24/48All TMC435 Treatment Groups
The Number of Participants With Abnormal Alanine Aminotransferase (ALT) Levels at Baseline Who Achieved Normalized ALT Levels at the End of Treatment (EOT)39373935150
SecondaryPlasma Concentrations of TMC435

The table below shows median (range) predose plasma concentration (C0h) values and median (range) average steady-state plasma concentration (Css,av) values for participants in each of the 4 TMC435 treatment groups.

Time frame:
Two random blood samples taken at least 2 hours apart at Weeks 2, 4, 8, 12, 16, and 24
Reported as:
Median · ng/mL
Plasma Concentrations of TMC435
ng/mLTMC435 75 mg 12 Wks + PR 24/48TMC435 75 mg 24 Wks + PR 24/48TMC435 150 mg 12 Wks + PR 24/48TMC435 150 mg 24 Wks + PR 24/48
Coh240.9 (0 to 1927)213.6 (40 to 2124)1123.3 (91 to 13771)1176.7 (0 to 9875)
Css, av413.6 (6 to 2091)374.0 (151 to 2385)1661.8 (123 to 15868)1501.6 (47 to 11648)
SecondaryArea Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC24h) for TMC435

The table below shows the median (range) AUC24h values for TMC435 for participants in each of the 4 TMC435 treatment groups. Two blood samples taken at least 2 hours apart from each other for determination of TMC435 plasma pharmacokinetics were obtained in all participants on Weeks 2, 4, 8, 12, 16, and 24 to obtain Bayesian estimates of TMC435 AUC24h (overall exposure).

Time frame:
Two random blood samples taken at least 2 hours apart at Weeks 2, 4, 8, 12, 16, and 24
Reported as:
Median · ng*h/mL
Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC24h) for TMC435
ng*h/mLTMC435 75 mg 12 Wks + PR 24/48TMC435 75 mg 24 Wks + PR 24/48TMC435 150 mg 12 Wks + PR 24/48TMC435 150 mg 24 Wks + PR 24/48
Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC24h) for TMC4359926.4 (138 to 50179)8976.8 (3615 to 57243)39884.0 (2948 to 380830)36038.8 (1134 to 279550)

Adverse events

Collected over 72 weeks. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
TMC435 75 mg 12 Wks + PR 24/48—9/78 (11.5%)76/78 (97.4%)
TMC435 75 mg 24 Wks + PR 24/48—4/75 (5.3%)75/75 (100%)
TMC435 150 mg 12 Wks + PR 24/48—4/77 (5.2%)74/77 (96.1%)
TMC435 150 mg 24 Wks + PR 24/48—3/79 (3.8%)77/79 (97.5%)
Placebo 24 Wks + PR48—10/77 (13%)75/77 (97.4%)
Most frequent serious events
Showing 10 of 35
Most frequent serious events
EventTMC435 75 mg 12 Wks + PR 24/48TMC435 75 mg 24 Wks + PR 24/48TMC435 150 mg 12 Wks + PR 24/48TMC435 150 mg 24 Wks + PR 24/48Placebo 24 Wks + PR48
Upper respiratory tract infectionInfections and infestations0/781/750/770/790/77
NauseaGastrointestinal disorders0/781/750/770/790/77
Small intestinal obstructionGastrointestinal disorders0/781/750/770/790/77
Ocular vasculitisEye disorders0/781/750/770/790/77
HeadacheNervous system disorders0/781/750/770/791/77
AppendicitisInfections and infestations0/780/750/770/791/77
Subcutaneous abscessInfections and infestations0/780/750/770/791/77
Vulval abscessInfections and infestations0/780/750/770/791/77
ColitisGastrointestinal disorders0/780/751/770/790/77
VomitingGastrointestinal disorders0/780/750/770/791/77
Most frequent other events
Showing 10 of 75
Most frequent other events
EventTMC435 75 mg 12 Wks + PR 24/48TMC435 75 mg 24 Wks + PR 24/48TMC435 150 mg 12 Wks + PR 24/48TMC435 150 mg 24 Wks + PR 24/48Placebo 24 Wks + PR48
HeadacheNervous system disorders41/7834/7535/7732/7940/77
FatigueGeneral disorders26/7835/7532/7738/7937/77
PruritusSkin and subcutaneous tissue disorders25/7817/7530/7724/7935/77
Influenza like illnessGeneral disorders21/7832/7518/7727/7929/77
NauseaGastrointestinal disorders26/7816/7520/7724/7921/77
NeutropeniaBlood and lymphatic system disorders15/7823/7519/7718/7916/77
InsomniaPsychiatric disorders19/7814/7523/7713/7923/77
Dry skinSkin and subcutaneous tissue disorders12/7812/7517/7722/7914/77
RashSkin and subcutaneous tissue disorders21/7810/7516/7718/7918/77
AstheniaGeneral disorders20/7812/7518/7713/7916/77

Baseline characteristics

Age, Continuous
Age, Continuous(years)TMC435 75 mg 12 Wks + PR 24/48TMC435 75 mg 24 Wks + PR 24/48TMC435 150 mg 12 Wks + PR 24/48TMC435 150 mg 24 Wks + PR 24/48Placebo 24 Wks + PR48Total
Median47 (19 to 66)46 (18 to 67)47 (18 to 69)47 (18 to 69)45 (21 to 67)46.5 (18 to 69)
Sex: Female, Male
Sex: Female, Male(Participants)TMC435 75 mg 12 Wks + PR 24/48TMC435 75 mg 24 Wks + PR 24/48TMC435 150 mg 12 Wks + PR 24/48TMC435 150 mg 24 Wks + PR 24/48Placebo 24 Wks + PR48Total
Female3828343538173
Male4047434439213
Region of Enrollment
Region of Enrollment(participants)TMC435 75 mg 12 Wks + PR 24/48TMC435 75 mg 24 Wks + PR 24/48TMC435 150 mg 12 Wks + PR 24/48TMC435 150 mg 24 Wks + PR 24/48Placebo 24 Wks + PR48Total
Asia Pacific99713442
Europe5252564458262
North-America171414221582
08

Study locations

73 sites
  • Los Angeles, California, United States
  • Jacksonville, Florida, United States
  • Orlando, Florida, United States
  • Palm Harbor, Florida, United States
  • Chicago, Illinois, United States
  • New Orleans, Louisiana, United States
  • Saint Paul, Minnesota, United States
  • New York, New York, United States
  • Chapel Hill, North Carolina, United States
  • Cincinnati, Ohio, United States
  • Germantown, Tennessee, United States
  • Charlottesville, Virginia, United States
  • Concord, Australia
  • Darlinghurst, Australia
  • Fitzroy, Australia
  • Melbourne, Australia
  • Sydney, Australia
  • Woolloongabba N/A, Australia
  • Wien, Austria
  • Brugge, Belgium
  • Brussels, Belgium
  • Bruxelles, Belgium
  • Edegem, Belgium
  • Gent, Belgium
  • Leuven, Belgium
  • Roeselare, Belgium
  • Calgary, Alberta, Canada
  • Toronto, Ontario, Canada
  • Montreal, Quebec, Canada
  • Aarhus, Denmark
  • Copenhagen, Denmark
  • Hvidovre N/A, Denmark
  • Kolding, Denmark
  • Odense N/A, Denmark
  • Clichy, France
  • Creteil N/A, France
  • Grenoble, France
  • Lyon, France
  • Nice, France
  • Paris, France
  • Vandoeuvre Les Nancy, France
  • Berlin, Germany
  • Düsseldorf, Germany
  • Frankfurt A. M., Germany
  • Freiburg, Germany
  • Hamburg, Germany
  • Hannover, Germany
  • Köln, Germany
  • Stuttgart, Germany
  • Würzburg, Germany
  • Auckland, New Zealand
  • Christchurch, New Zealand
  • Hamilton, New Zealand
  • Bergen, Norway
  • Nordbyhagen, Norway
  • Oslo, Norway
  • Tromsø, Norway
  • Bialystok, Poland
  • Bydgoszcz, Poland
  • Czeladz, Poland
  • Kielce, Poland
  • Lodz, Poland
  • Warschau, Poland
  • Moscow, Russian Federation
  • Nizhny Novgorod, Russian Federation
  • Saint-Petersburg, Russian Federation
  • Samara, Russian Federation
  • Smolensk, Russian Federation
  • St Petersburg, Russian Federation
  • Barcelona, Spain
  • Madrid, Spain
  • Sevilla N/A, Spain
  • Valencia, Spain
09

References and documents

Publications

  • Lenz O, Verbinnen T, Fevery B, Tambuyzer L, Vijgen L, Peeters M, Buelens A, Ceulemans H, Beumont M, Picchio G, De Meyer S. Virology analyses of HCV isolates from genotype 1-infected patients treated with simeprevir plus peginterferon/ribavirin in Phase IIb/III studies. J Hepatol. 2015 May;62(5):1008-14. doi: 10.1016/j.jhep.2014.11.032. Epub 2014 Nov 28. PubMed 25445400 ↗
  • Scott J, Rosa K, Fu M, Cerri K, Peeters M, Beumont M, Zeuzem S, Evon DM, Gilles L. Fatigue during treatment for hepatitis C virus: results of self-reported fatigue severity in two Phase IIb studies of simeprevir treatment in patients with hepatitis C virus genotype 1 infection. BMC Infect Dis. 2014 Aug 26;14:465. doi: 10.1186/1471-2334-14-465. PubMed 25164700 ↗
  • Fried MW, Buti M, Dore GJ, Flisiak R, Ferenci P, Jacobson I, Marcellin P, Manns M, Nikitin I, Poordad F, Sherman M, Zeuzem S, Scott J, Gilles L, Lenz O, Peeters M, Sekar V, De Smedt G, Beumont-Mauviel M. Once-daily simeprevir (TMC435) with pegylated interferon and ribavirin in treatment-naive genotype 1 hepatitis C: the randomized PILLAR study. Hepatology. 2013 Dec;58(6):1918-29. doi: 10.1002/hep.26641. Epub 2013 Oct 11. PubMed 23907700 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jun 16, 2014, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00882908
Lead sponsor
Tibotec Pharmaceuticals, Ireland
Responsible party
Sponsor
First posted
Apr 17, 2009
Start date
Jun 2009
Primary completion
Apr 2010
Completion
Apr 2011
Results posted
Jun 16, 2014
Last update
Jun 16, 2014

Study contacts

Tibotec Pharmaceuticals, Ireland Clinical Trial
study director · Tibotec Pharmaceuticals, Ireland

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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