Hepatitis C, ChronicPhase 2NCT00561353
A Study of TMC435350 Administered With or Without Standard of Care Therapy in Participants With Genotype 1 Hepatitis C Virus Infection
A Phase 2 study testing TMC435, Peginterferon (PegIFNα-2a) and Ribavirin in people with Hepatitis C, Chronic, run by Tibotec Pharmaceuticals, Ireland at 24 sites in 6 countries.
Trial summary
The purpose of this study is to investigate how efficient TMC435350 will work against the Hepatitis C virus genotype 1 (genotypes refer to the genetic constitution of the virus) and what the concentrations of TMC435350 in the blood are with or without pegylated interferon alpha-2a (PegIFNa-2a) or PegIFNa-2a plus… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Hepatitis C, Chronic
- What is being tested?
- TMC435, Peginterferon (PegIFNα-2a) and Ribavirin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 121 participants
- Where
- 24 sitesin 6 countries
- Study dates
- Jan 2008to May 2010
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Inclusion Criteria: - Documented chronic genotype 1 Hepatitis C infection - Able to comply with the protocol requirements and having good accessible veins - Amount of virus in the blood (HCV RNA) >= 10.000 IU/mL, at screening - Bodyweight as defined by a Quetelet Index (Body Mass Index [BMI]) between 18 and 32 kg/m², extremes included Exclusion Criteria: - Evidence of liver cirrhosis or decompensated liver disease or any other form of non-viral hepatitis - Participants receiving or having received treatment with polymerase inhibitor or protease inhibitor, or Standard of Care therapy with COPEGUS (ribavirin) and PEGASYS (peginterferon alpha-2a) for treatment for HCV during the 6 months before screening - Male participants with female partners of childbearing potential not agreeing to use a reliable birth control method, Female, except if postmenopausal for over 2 years, or posthysterectomy, or post-tubal ligation (without reversal operation) - History or evidence of current use of alcohol, barbiturate, amphetamine, recreational or narcotic drug use, which would compromise the participant 's safety and/or compliance. A positive urine drug test at screening. Urine will be tested to check the current use of amphetamines, cocaine, and opioids (with the exclusion of methadone) - Participants having at least one lab toxicity that is found to be clinically significant - Participants co-infected with HIV, or Hepatitis A or B, or hepatitis B surface antigen, or active tuberculosis at screening, participants with prolonged QTc (>480 ms) value or any cardiac disease at screening, or any active clinically significant disease (e.g., cardiac dysfunction, cardio(myo)pathy, cardiac insufficiency), or medical history or physical examination findings during screening that, in the Investigator's opinion, would compromise the outcome of the trial - Participants having uncontrolled/unstable diabetes, epilepsy, a manifest psychiatric disease, non-stable methadone (or equivalent drug) use or participants having any other unstable disease, participants enrolled in another clinical trial within 90 days prior to screening
Trial locations and contacts
24 sites in 6 countries.
24 sites in 6 countries
Germany7 sites
Study site
Berlin
Study site
Düsseldorf
Study site
Freiburg im Breisgau
Study site
Hamburg
Study site
Hanover
Study site
Kiel
Study site
München
France6 sites
Study site
Clichy
Study site
Lyon
Study site
Marseille
Study site
Paris
Study site
Pessac
Study site
Vandœuvre-lès-Nancy
Belgium4 sites
Study site
Bruges
Study site
Brussels
Study site
Edegem
Study site
Ghent
Poland4 sites
Study site
Bialystok
Study site
Kielce
Study site
Lodz
Study site
Warsaw
About this study
Official title: A Blinded, Randomized, Placebo-controlled Trial in Genotype 1 Hepatitis C-Infected Subjects to Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of Repeated Doses of TMC435350, With or Without Peginterferon Alpha-2a and Ribavirin
The purpose of this study is to investigate how efficient TMC435350 will work against the Hepatitis C virus genotype 1 (genotypes refer to the genetic constitution of the virus) and what the concentrations of TMC435350 in the blood are with or without pegylated interferon alpha-2a (PegIFNa-2a) or PegIFNa-2a plus ribavirin.
Read the detailed description
This is a blinded (participant and study staff will not know the identity of assigned treatments), randomized (participants assigned to treatment by chance), placebo-controlled (a term used to describe a method of research in which an inactive substance referred to as a placebo is given to one group of participants, while the treatment being tested is given to another group) study to assess the effectiveness, safety, tolerability, and pharmacokinetics (to test the concentration of study drug in the blood over time) of different dose regimens of TMC435350 (hereafter referred to as TMC435) given alone or in combination with peginterferon alpha-2a (PegIFNa-2a) and ribavirin. TMC435 is a new drug that is development for the treatment of Hepatitis C virus (HCV) infection and belongs to a class of drugs that work by blocking an enzyme (protease) that the HCV needs to replicate. The combination of PegIFNa-2a and ribavirin are current standard of care (SoC) therapy for patients with chronic HCV infection. Approximately 72 participants with HCV infection who have never been treated for HCV infection (referred to as treatment-naïve participants) and 36 participants who have been treated for HCV infection (referred to as treatment-experienced participants) who did not respond to previous therapy with interferon (IFN) and who did not discontinue previous anti-HCV therapy because of adverse events [AEs]) will be included in this study. Two blinded placebo-controlled groups (referred to as "cohorts") of treatment-naïve participants will be sequentially initiated TMC435 to ensure that a higher dose is only administered if the previous lower dose is found safe and tolerable. The first group (Cohort 1) of treatment-naïve participants will receive low-doses of TMC435 or placebo for 7 days followed by 21 days of combined tritherapy with PegIFNa-2a and ribavirin OR participants will receive 28 days of tritherapy (TMC435 or placebo + PegIFNa-2a and ribavirin). After review of data from Cohort 1, a second group (Cohort 2) of treatment-naïve participants will be given higher doses of TMC435 or placebo in the same manner described for the first cohort. A third group (Cohort 3) of participants previously planned in the study will not be enrolled. After review of data from Cohort 2, a fourth group (Cohort 4) of treatment-experienced participants will be given 28 days of TMC435 (or placebo) as tritherapy with PegIFNa-2a and ribavirin to determine the maximum tolerated dose of TMC435. In addition, up to 10 HCV-infected individuals (who participated in study TMC435350-TiDP16-C101 (ClinicalTrials.gov registry number NCT00938899) will comprise Cohort 5 and will be given 28 days of TMC435 at a dose previously determined to be safe and efficacious as tritherapy with PegIFNa-2a and ribavirin. Blood samples will be taken from participants at protocol-specified time points to determine plasma concentrations of TMC435 and ribavirin and safety will be monitored throughout the study. Individuals will participate in this study for up 54 weeks (includes up to 6 weeks during the screening period followed by up to 4 weeks of study treatment with TMC435 (or placebo) and up to a maximum of 44 weeks of treatment with PegIFNa-2a and ribavirin.
- Conditions
- Hepatitis C, Chronic
- Being tested
- TMC435, Placebo, Peginterferon (PegIFNα-2a), Ribavirin
- Keywords
- Hepatitis C, Chronic, Tibotec, TMC435350-TiDP16-C201, TMC435350-C201, TMC435, PEGASYS (peginterferon alpha-2a, PegIFNα-2a), COPEGUS (ribavirin)
- Medical subject headings
- Hepatitis C, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TMC435Drug
TMC435 25 mg, 75 mg, 150 mg, or 200 mg capsules taken orally (by mouth) once daily for 21 or 28 days.
PlaceboDrug
Placebo capsules identical in appearance to TMC435 capsules taken orally (by mouth) once daily for 28 days.
Peginterferon (PegIFNα-2a)Drug
Also called PEGASYS
One subcutaneous (under the skin) injection containing 0.5 mL solution with 180 mcg PegIFNα-2a on Days 1, 8, 15, and 22
RibavirinDrug
Also called COPEGUS
200-mg tablets of ribavirin (body-weight adjusted dose) taken orally (by mouth) twice daily for 21 or 28 days in Cohorts 1 and 2 and for 28 days in Cohorts 4 and 5.
| Study group | Role | What they receive |
|---|---|---|
| TMC435 25 mg (Cohort 1/Panel A and B) | Experimental | Treatment-naïve participants received TMC435 25 mg once daily for 7 days followed by TMC435 25 mg once daily coadministered with peginterferon alpha-2a (PegIFNα-2a) (P) and ribavirin (R) for 21 days (Panel A) OR TMC435 25 mg once daily coadministered with PR for 28 days (Panel B). Receives: Drug: TMC435; Drug: Peginterferon (PegIFNα-2a); Drug: Ribavirin |
| TMC435 75mg (Cohort 1/Panel A and B) | Experimental | Treatment-naïve participants received TMC435 75 mg once daily for 7 days followed by TMC435 75 mg once daily for 21 days with PegIFNα-2a (P) and ribavirin (R) OR TMC435 75 mg once daily coadministered with PR for 28 days (Panel B). Receives: Drug: TMC435; Drug: Peginterferon (PegIFNα-2a); Drug: Ribavirin |
| Placebo (Cohort 1/Panel A and B) | Placebo comparator | Treatment-naïve participants received placebo (identical in appearance to TMC435 25/75 mg) once daily for 7 days followed by placebo once daily coadministered with PegIFNα-2a (P) and ribavirin (R) for 21 days (Panel A) OR and Placebo once daily coadministered with PR for 28 days (Panel B). Receives: Drug: Placebo; Drug: Peginterferon (PegIFNα-2a); Drug: Ribavirin |
| TMC435 200 mg (Cohort 2, Panel A and B) | Experimental | Treatment-naïve participants received TMC435 200 mg once daily for 7 days followed by TMC435 200 mg once daily coadministered with PegIFNα-2a (P) and ribavirin (R) for 21 days (Panel A) OR TMC435 200 mg once daily coadministered with PR for 28 days (Panel B). Receives: Drug: TMC435; Drug: Peginterferon (PegIFNα-2a); Drug: Ribavirin |
| Placebo (Cohort 2/Panel A and B) | Placebo comparator | Treatment-naïve participants received placebo (identical in appearance to TMC435 200 mg) once daily for 7 days followed by placebo once daily coadministered with PegIFNα-2a (P) and ribavirin (R) for 21 days (Panel A) OR placebo once daily coadministered with PR for 28 days (Panel B). Receives: Drug: Placebo; Drug: Peginterferon (PegIFNα-2a); Drug: Ribavirin |
| TMC435 75 mg (Cohort 4/Panel C) | Experimental | Treatment-experienced non-responders received TMC435 75 mg once daily coadministered with PegIFNα-2a and ribavirin for 28 days. Receives: Drug: TMC435; Drug: Peginterferon (PegIFNα-2a); Drug: Ribavirin |
| TMC435 150 mg (Cohort 4/Panel C) | Experimental | Treatment-experienced non-responders received TMC435 150 mg once daily coadministered with PegIFNα-2a and ribavirin for 28 days. Receives: Drug: TMC435; Drug: Peginterferon (PegIFNα-2a); Drug: Ribavirin |
| TMC435 200 mg (Cohort 4/Panel C) | Experimental | Treatment-experienced non-responders received TMC435 200 mg once daily coadministered with PegIFNα-2a and ribavirin for 28 days. Receives: Drug: TMC435; Drug: Peginterferon (PegIFNα-2a); Drug: Ribavirin |
| Placebo (Cohort 4/Panel C) | Placebo comparator | Treatment-experienced non-responders received placebo once daily coadministered with PegIFNα-2a and ribavirin for 28 days. Receives: Drug: Placebo; Drug: Peginterferon (PegIFNα-2a); Drug: Ribavirin |
| TMC435 200 mg (Cohort 5/Panel D) | Experimental | Treatment-experienced relapsers received TMC435 200 mg once daily coadministered with PegIFNα-2a and ribavirin for 28 days. Receives: Drug: TMC435; Drug: Peginterferon (PegIFNα-2a); Drug: Ribavirin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) at Week 4 in Treatment-Naïve HCV-Infected Participants (Cohort 1 and 2, Panel A)
The table below shows the change from Baseline in plasma levels of HCV RNA at Week 4 following treatment with TMC435 or placebo as for 7 days followed by TMC435 or placebo coadministered with ribavirin for 21 days + peginterferon alpha-2a (PegIFNα-2a) on Days 1, 8, 15, and 22 in treatment-naïve HCV-infected participants. (A treatment-naive participant is someone who has never taken drugs for their HCV infection).
Measured: Week 4
Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) at Week 4 in Treatment-Naïve HCV-Infected Participants (Cohort 1 and 2, Panel B)
The table below shows the change from Baseline in plasma levels of HCV RNA at Week 4 following treatment with TMC435 or placebo coadministered with ribavirin for 28 days + peginterferon alpha-2a (PegIFNα-2a) on Days 1, 8, 15, and 22 in treatment-naïve HCV-infected participants. (A treatment-naive participant is someone who has never taken drugs for their HCV infection).
Measured: Week 4
Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) at Week 4 in Treatment-Experienced HCV-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D)
The table below shows the change from Baseline in plasma levels of HCV RNA at Week 4 following treatment with TMC435 or placebo coadministered with ribavirin for 28 days + peginterferon alpha-2a (PegIFNα-2a) on Days 1, 8, 15, and 22 in treatment-experienced participants considered non-responders (defined as participants who achieved less than a 2 log10 IU/mL decline from baseline in plasma HCV RNA levels after 12 weeks of previous interferon [IFN]-based therapy [pegylated or non-pegylated]) or relapsers (defined as a participant with undetectable plasma HCV RNA at the end of treatment of previous IFN-based therapy and subsequent confirmed detectable plasma HCV RNA levels during follow-up).
Measured: Week 4
Secondary outcomes (25)
Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) on Day 7 in Treatment-Naïve HCV-Infected Participants (Cohort 1 and 2, Panel A)
The table below shows the change from Baseline in plasma levels of HCV RNA on Day 7 (at Week 1) following treatment with TMC435 or placebo for 7 days followed by TMC435 or placebo coadministered with ribavirin for 21 days + peginterferon alpha-2a (PegIFNα-2a) on Days 8, 15, and 22 in treatment-naïve HCV-infected participants. (A treatment-naive participant is someone who has never taken drugs for their HCV infection).
Measured: Day 7
Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) on Day 7 in Treatment-Naïve HCV-Infected Participants (Cohort 1 and 2, Panel B)
The table below shows the change from Baseline in plasma levels of HCV RNA on Day 7 (at Week 1) following treatment with TMC435 or placebo coadministered with ribavirin for 28 days + peginterferon alpha-2a (PegIFNα-2a) on Days 1, 8, 15, and 22 in treatment-naïve HCV-infected participants (A treatment-naive participant is someone who has never taken drugs for their HCV infection).
Measured: Day 7
Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) on Day 7 in Treatment-Experienced HCV-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D)
The table below shows the change from Baseline in plasma levels of HCV RNA on Day 7 (Week 1) following treatment with TMC435 or placebo coadministered with ribavirin for 28 days + peginterferon alpha-2a (PegIFNα-2a) on Days 1, 8, 15, and 22 in treatment-experienced participants considered non-responders (defined as participants who achieved less than a 2 log10 IU/mL decline from baseline in plasma HCV RNA levels after 12 weeks of previous interferon [IFN]-based therapy [pegylated or non-pegylated]) or relapsers (defined as a participant with undetectable plasma HCV RNA at the end of treatment of previous IFN-based therapy and subsequent confirmed detectable plasma HCV RNA levels during follow-up).
Measured: Day 7
Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A)
The table below shows the number of treatment-naïve HCV-infected participants treated with TMC435 or placebo for 7 days followed by TMC435 or placebo coadministered with ribavirin for 21 days + peginterferon alpha-2a (PegIFNα-2a) on Days 8, 15, and 22 who had the following virologic responses: plasma levels of HCV ribonucleic acid (RNA) of greater than or equal to 2 log10 decline from Baseline; plasma levels of HCV RNA below the limit of quantification (ie, less than [<] 25 IU/mL detectable or undetectable); plasma levels of HCV RNA below the limit of detection (ie, <25 IU/mL undetectable); plasma levels of HCV RNA <100 IU/mL; and plasma levels of HCV RNA <1000 at the time points listed. See "treatment-naive" defined above.
Measured: Day 2 or 3, Day 7, and Day 28
Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B)
The table below shows the number of treatment-naive HCV-Infected participants with the following virologic responses to treatment with TMC435 or placebo coadministered with ribavirin for 28 days + peginterferon alpha-2a (PegIFNα-2a) on Days 8, 15, and 22: plasma levels of HCV ribonucleic acid (RNA) of greater than or equal to 2 log10 decline from Baseline; plasma levels of HCV RNA below the limit of quantification (ie, less than [<] 25 IU/mL detectable or undetectable); plasma levels of HCV RNA below the limit of detection (ie, <25 IU/mL undetectable); plasma levels of HCV RNA <100 IU/mL; and plasma levels of HCV RNA <1000 at the time points listed. See "treatment-naive" defined above.
Measured: Day 2 or 3, Day 7, and Day 28
Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D)
The table below shows the number of treatment-experienced participants (non-responders and relapsers, see defined above) with the following virologic responses to treatment with TMC435 or placebo coadministered with ribavirin for 28 days + peginterferon alpha-2a (PegIFNα-2a) on Days 1, 8, 15, and 22: plasma levels of HCV ribonucleic acid (RNA) of greater than or equal to 2 log10 decline from Baseline; plasma levels of HCV RNA below the limit of quantification (ie, less than [<] 25 IU/mL detectable or undetectable); plasma levels of HCV RNA below the limit of detection (ie, <25 IU/mL undetectable); plasma levels of HCV RNA <100 IU/mL; and plasma levels of HCV RNA <1000 at the time points listed. Note: in the table below, the number of participants (n) analyzed in the TMC435 200 mg (Cohort 4, Panel B) on Day 28 (Week 4) was n=4.
Measured: Day 2 or 3, Day 7, and Day 28
Virologic Response Parameters in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined)
The table below shows the number of treatment-naïve participants in the treatment groups for Cohort 1 (Panel A and B combined) and in Cohort 2 (Panel A and B combined) who met the following virologic response parameters: rapid virological response (RVR) defined as having undetectable plasma HCV ribonucleic acid (RNA) at Week 4; early virologic response (EVR) defined as change from baseline in plasma HCV RNA of greater than or equal to 2 log 10 at Week 12); a complete EVR (cEVR) defined as a complete EVR having undetectable plasma HCV RNA at Week 12); an extended RVR (eRVR) defined as undetectable plasma HCV RNA at Week 4 and 12; and a partial response defined as EVR but not reaching undetectability while on treatment.
Measured: Week 4 (RVR), Week 12 (EVR, cEVR, and partial response), and Week 4 and 12 (eRVR)
Virologic Response Parameters Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D)
The table below shows the number of treatment-experienced participants (non-responders and relapsers, see defined above) treated with TMC435 or placebo coadministered with ribavirin for 28 days + peginterferon alpha-2a (PegIFNα-2a) on Days 1, 8, 15, and 22 who met the following virologic response parameters: rapid virological response (RVR) defined as having undetectable plasma HCV ribonucleic acid (RNA) at Week 4; early virologic response (EVR) defined as change from baseline in plasma HCV RNA of greater than or equal to 2 log 10 at Week 12; a complete EVR (cEVR) defined as a EVR having undetectable plasma HCV RNA at Week 12; an extended RVR (eRVR) defined as undetectable plasma HCV RNA at Week 4 and 12; and a partial response defined as EVR but not reaching undetectability while on treatment.
Measured: Week 4 (RVR), Week 12 (EVR, cEVR, and partial response), and Week 4 and 12 (eRVR)
Initial Suboptimal Responses Following Treatment With TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A)
The table below shows the number of treatment-naïve participants with an initial suboptimal response defined as less than 2 log10 change in plasma level of hepatitis C virus (HCV) ribonucleic acid (RNA) on Day 2 or 3 (depending when visit was scheduled) following treatment with TMC435 or placebo for 7 days followed by TMC435 or placebo coadministered with ribavirin for 21 days + peginterferon alpha-2a (PegIFNα-2a) on Days 8, 15, and 22. See "treatment-naive" defined above.
Measured: Day 2 or 3
Initial Suboptimal Responses Following Treatment With TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B)
The table below shows the number of treatment-naïve participants with an initial suboptimal response defined as less than 2 log10 change in plasma plasma level of hepatitis C virus (HCV) ribonucleic acid (RNA) on Day 2 or 3 (depending when visit was scheduled) after treatment with TMC435 or placebo coadministered with ribavirin for 28 days + peginterferon alpha-2a (PegIFNα-2a) on Days 1, 8, 15, and 22. See "treatment-naive" defined above.
Measured: Day 2 or 3
Initial Suboptimal Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D)
The table below shows the number of treatment-experienced participants (non-responders and relapsers, see defined above) with an initial suboptimal response defined as less than 2 log10 change of plasma in plasma level of HCV ribonucleic acid (RNA) at Day 2 or 3 (depending when visit was scheduled) treated with TMC435 or placebo coadministered with ribavirin for 28 days + peginterferon alpha-2a (PegIFNα-2a) on Days 1, 8, 15, and 22.
Measured: Day 2 or 3
Viral Breakthrough in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1, Panel A and B)
The table below shows the number of treatment-naïve participants with viral breakthrough, defined as a confirmed increase of greater than 1 log10 IU/mL in plasma HCV ribonucleic acid (RNA) level from the lowest level reached, or a confirmed plasma HCV RNA level of greater than 100 IU/mL in participants whose plasma HCV RNA had previously been below the limit of quantification (25 IU/mL detectable) or undetectable (less than 25 IU/mL undetectable) after treatment with TMC435 or placebo for 7 days followed by TMC435 or placebo coadministered with ribavirin for 21 days + peginterferon alpha-2a (PegIFNα-2a) on days 8, 15, and 22 (Panel A) and after treatment with TMC435 or placebo coadministered with ribavirin for 28 days + PegIFNα-2a on Days 1, 8, 15, and 22 (Panel B).
Measured: 4 Weeks (Wks), 44 Wks, and 48 Wks
Viral Breakthrough in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D)
The table below shows the number of treatment-experienced participants (non-responders and relapsers, see defined above) with viral breakthrough, defined as a confirmed increase of greater than 1 log10 IU/mL in plasma HCV ribonucleic acid (RNA) level from the lowest level reached), or a confirmed plasma HCV RNA level of greater than 100 IU/mL in participants whose plasma HCV RNA had previously been below the limit of quantification (25 IU/mL detectable) or undetectable (less than 25 IU/mL undetectable) treated with TMC435 or placebo coadministered with ribavirin for 28 days + peginterferon alpha-2a (PegIFNα-2a) on Days 1, 8, 15, and 22.
Measured: 4 Weeks (Wks), 44 Wks, and 48 Wks
Viral Relapse in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined)
The table below shows the number of treatment-naïve participants with viral relapse (defined as having confirmed detectable plasma level of HCV ribonucleic acid [RNA] during the follow-up period in participants with undetectable plasma HCV RNA [less than 25 IU/mL undetectable] at the end of treatment) for the treatment groups in Cohort 1 (Panel A and B combined) and in Cohort 2 (Panel A and B combined). See "treatment-naïve" defined above.
Measured: Up to Week 72
Viral Relapse in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D)
The table below shows the number of treatment-experienced participants combined (non-responders and relapsers, see defined above) with viral relapse, defined as having confirmed detectable plasma level of HCV ribonucleic acid (RNA) during the follow-up period in participants with undetectable plasma HCV RNA (less than 25 IU/mL undetectable) at the end of treatment who received TMC435 or placebo coadministered with ribavirin for 28 days + peginterferon alpha-2a (PegIFNα-2a) on Days 1, 8, 15, and 22.
Measured: Up to Week 72
Sustained Virologic Response (SVR) in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined)
The table below shows the number of treatment-naïve participants with an SVR to treatment (defined as having an undetectable plasma level of HCV ribonucleic acid after the last planned dose of treatment) for the treatment groups in Cohort 1 (Panel A and B combined) and in Cohort 2 (Panel A and B combined). SVR was measured at 4, 8, 12, and 24 weeks after the last dose of treatment (SVR4, SVR8, SVR12, and SVR24, respectively). See "treatment-naïve" defined above.
Measured: SVR4 (Week 52), SVR8 (Week 56), SVR12 (Week 60), and SVR24 (Week 72)
Sustained Virologic Response (SVR) in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D)
The table below shows the number of treatment-experienced participants (non-responders and relapsers, see defined above) in each treatment group in Cohort 4, Panel C and in Cohort 5, Panel D with an SVR to treatment defined as having an undetectable plasma level of HCV ribonucleic acid after the last planned dose of the entire treatment regimen. SVR was measured at 4, 8, 12, and 24 weeks after the last dose of treatment (SVR4, SVR8, SVR12, and SVR24, respectively).
Measured: SVR4 (Week 52), SVR8 (Week 56), SVR12 (Week 60), and SVR24 (Week 72)
Maximum Plasma Concentration (Cmax) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B)
The table below shows the mean (standard deviation) Cmax for treatment-naïve participants at selected time points who were treated with TMC435 for 7 days followed by TMC435 coadministered with ribavirin for 21 days + peginterferon alpha-2a (PegIFNα-2a) on Days 8, 15, and 22 (Panel A) and with TMC435 coadministered with ribavirin for 28 days + PegIFNα-2a on Days 1, 8, 15, and 22 (Panel B). See "treatment-naïve" defined above. The number of participants analyzed at Day 28 in the 6 treatment groups listed below from left to right were 9, 8, 7, 9, 9, and 10.
Measured: Days 1 and 28 (predose and 0.5, 1, 2, 4, 6, 8, and 10 hours postdose)
Maximum Plasma Concentration (Cmax) of TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D)
The table below shows the mean (standard deviation) Cmax for treatment-experienced participants (non-responders and relapsers, see defined above) following treatment with TMC435 coadministered with ribavirin for 28 days + peginterferon alpha-2a (PegIFNα-2a) on Days 1, 8, 15, and 22. The number of participants analyzed at Day 28 in the 4 treatment groups listed below from left to right were 8, 8, 10, and 3.
Measured: Days 1 and 28 (predose and 0.5, 1, 2, 4, 6, 8, and 10 hours postdose)
Predose Plasma Concentration (C0h) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B)
The table below shows mean (standard deviation) of C0h of TMC435 at selected time points following treatment with TMC435 for 7 days followed by TMC435 coadministered with ribavirin for 21 days + peginterferon alpha-2a (PegIFNα-2a) on Days 8, 15, and 22 (Panel A) or with TMC435 coadministered with ribavirin for 28 days + PegIFNα-2a on Days 1, 8, 15, and 22 (Panel B) in treatment-naïve participants (see "treatment-naïve" defined above).The number of participants analyzed at Day 28 in the 6 treatment groups listed below from left to right were 9, 9, 8, 9, 9, and 10.
Measured: Day 2 (predose) and Day 28 (predose and 0.5, 1, 2, 4, 6, 8, and 10 hours postdose)
Predose Plasma Concentration (C0h) of TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D)
The table below shows mean (standard deviation) of C0h for treatment-experienced participants (non-responders and relapsers, see defined above) following treatment with TMC435 coadministered with ribavirin for 28 days + peginterferon alpha-2a (PegIFNα-2a) on Days 1, 8, 15, and 22. The number of participants analyzed at Day 2 and Day 28 differed as follows: At Day 2, the number of participants in the 4 treatment groups (from left to right) were 8, 7, 10, and 5; the number of participants analyzed at Day 28 in the 4 treatment groups (from left to right) were 9, 8, 10, and 4.
Measured: Day 2 (predose) and Day 28 (predose and 0.5, 1, 2, 4, 6, 8, and 10 hours postdose)
Average Steady-state Plasma Concentration (Css,av) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B)
The table below shows mean (standard deviation)of Css,av for TMC435 in treatment-naïve HCV-infected participants at selected time points administered TMC435 for 7 days followed by TMC435 coadministered with ribavirin for 21 days + peginterferon alpha-2a (PegIFNα-2a) on Days 8, 15, and 22 (Panel A) and with TMC435 coadministered with ribavirin for 28 days + PegIFNα-2a on Days 1, 8, 15, and 22 (Panel B). See "treatment-naïve" defined above. The number of participants analyzed at Day 28 in the 6 treatment groups listed below from left to right were 9, 8, 7, 9, 9, and 10.
Measured: Day 7 (predose); Day 28 (predose and 0.5, 1, 2, 4, 6, 8, and 10 hours postdose) (Panel A, Cohorts 1 and 2) and Day 28 (predose and 0.5, 1, 2, 4, 6, 8, and 10 hours postdose) (Panel B, Cohorts 1 and 2)
Average Steady-state Plasma Concentration (Css,av) of TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D)
The table below shows mean (standard deviation) of Css,av for TMC435 in treatment-experienced HCV-infected participants (non-responders and relapsers, see defined above) at selected time points following treatment with TMC435 coadministered with ribavirin for 28 days + peginterferon alpha-2a (PegIFNα-2a) on Days 1, 8, 15, and 22.
Measured: Day 28 (predose and 0.5, 1, 2, 4, 6, 8, and 10 hours postdose)
Area Under the Plasma Concentration-time Curve From the Time of Administration to 24 Hours After Dosing (AUC24h) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B)
The table below shows mean (standard deviation) values of the area under the plasma concentration-time curve from time of administration to 24 hours after dosing for TMC435 in treatment-naïve HCV-infected participants administered TMC435 for 7 days followed by TMC435 coadministered with ribavirin for 21 days + peginterferon alpha-2a (PegIFNα-2a) on Days 8, 15, and 22 (Panel A) and with TMC435 coadministered with ribavirin for 28 days + PegIFNα-2a on Days 1, 8, 15, and 22 (Panel B).The number of participants analyzed at Day 28 in the 6 treatment groups listed below from left to right were 9, 8, 7, 9, 9, and 10.
Measured: Days 1 and 28 (predose and 0.5, 1, 2, 4, 6, 8, and 10 hours postdose)
Area Under the Plasma Concentration-time Curve From the Time of Administration to 24 Hours After Dosing (AUC24h) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D)
The table below shows mean (standard deviation) values of the area under the plasma concentration-time curve from time of administration to 24 hours after dosing for TMC435 in treatment-experienced HCV-infected participants considered non-responders (participants who achieved less than a 2 log10 IU/mL decline from baseline in plasma HCV ribonucleic acid (RNA) levels after 12 weeks of previous interferon [IFN]-based therapy [pegylated or non-pegylated]) or relapsers (defined as a participant with undetectable plasma HCV RNA at the end of treatment of previous IFN-based therapy and subsequent confirmed detectable plasma HCV RNA levels during follow-up at selected time points following treatment with TMC435 coadministered with ribavirin (RBV) for 28 days + peginterferon alpha-2a (PegIFNα-2a) on Days 1, 8, 15, and 22. The number of participants analyzed at Day 28 in the 4 treatment groups listed below from left to right was 8, 7, 10, and 3.
Measured: Days 1 and 28 (predose and 0.5, 1, 2, 4, 6, 8, and 10 hours postdose)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Nov 2007 (estimated)
- Study startJan 2008
- Primary completionDec 2008
- Study completionMay 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Hepatitis C, ChronicStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 121 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tibotec Pharmaceuticals, Ireland
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Tibotec Pharmaceuticals, Ireland Clinical Trial, Study director, Tibotec Pharmaceuticals, Ireland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00561353
- Sponsor's protocol ID
- CR012607
- Other IDs
- TMC435350-TiDP16-C201
- Status last verified
- May 2014
- First submitted
- 19 Nov 2007
- Last updated
- 20 May 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Benguigui L, Le Gouzouguec S, Balanca B, Ristovski M, Putet G, Butin M, Guillois B, Beissel A. A Customizable Digital Cognitive Aid for Neonatal Resuscitation: A Simulation-Based Randomized Controlled Trial. Simul Healthc. 2024 Oct 1;19(5):302-308. doi: 10.1097/SIH.0000000000000790. Epub 2024 Apr 8.
PubMed 38587329Lenz O, de Bruijne J, Vijgen L, Verbinnen T, Weegink C, Van Marck H, Vandenbroucke I, Peeters M, Simmen K, Fanning G, Verloes R, Picchio G, Reesink H. Efficacy of re-treatment with TMC435 as combination therapy in hepatitis C virus-infected patients following TMC435 monotherapy. Gastroenterology. 2012 Nov;143(5):1176-1178.e6. doi: 10.1053/j.gastro.2012.07.117. Epub 2012 Aug 8.
PubMed 22885330Manns M, Reesink H, Berg T, Dusheiko G, Flisiak R, Marcellin P, Moreno C, Lenz O, Meyvisch P, Peeters M, Sekar V, Simmen K, Verloes R. Rapid viral response of once-daily TMC435 plus pegylated interferon/ribavirin in hepatitis C genotype-1 patients: a randomized trial. Antivir Ther. 2011;16(7):1021-33. doi: 10.3851/IMP1894.
PubMed 22024518
Study at a glance
From the registry record, last updated by the sponsor on 20 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Blinded, Randomized, Placebo-controlled Trial in Genotype 1 Hepatitis C-Infected Subjects to Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of Repeated Doses of TMC435350, With or Without Peginterferon Alpha-2a and Ribavirin
- ClinicalTrials.gov ID
- NCT00561353
- Acronym / sponsor ID
- CR012607
- Conditions
- Hepatitis C, Chronic
- Keywords
- Hepatitis C, Chronic, Tibotec, TMC435350-TiDP16-C201, TMC435350-C201, TMC435, PEGASYS (peginterferon alpha-2a, PegIFNα-2a), COPEGUS (ribavirin)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 121 participants (actual)
- Lead sponsor
- Tibotec Pharmaceuticals, IrelandIndustry (pharma, biotech, devices)
- Study start
- Jan 2008
- Primary completion
- Dec 2008 (actual)
- Study completion
- May 2010 (actual)
- First posted
- 20 Nov 2007 (estimated)
- Results
- Posted 6 Feb 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to investigate how efficient TMC435350 will work against the Hepatitis C virus genotype 1 (genotypes refer to the genetic constitution of the virus) and what the concentrations of TMC435350 in the blood are with or without pegylated interferon alpha-2a (PegIFNa-2a) or PegIFNa-2a plus ribavirin.
Detailed description
This is a blinded (participant and study staff will not know the identity of assigned treatments), randomized (participants assigned to treatment by chance), placebo-controlled (a term used to describe a method of research in which an inactive substance referred to as a placebo is given to one group of participants, while the treatment being tested is given to another group) study to assess the effectiveness, safety, tolerability, and pharmacokinetics (to test the concentration of study drug in the blood over time) of different dose regimens of TMC435350 (hereafter referred to as TMC435) given alone or in combination with peginterferon alpha-2a (PegIFNa-2a) and ribavirin. TMC435 is a new drug that is development for the treatment of Hepatitis C virus (HCV) infection and belongs to a class of drugs that work by blocking an enzyme (protease) that the HCV needs to replicate. The combination of PegIFNa-2a and ribavirin are current standard of care (SoC) therapy for patients with chronic HCV infection. Approximately 72 participants with HCV infection who have never been treated for HCV infection (referred to as treatment-naïve participants) and 36 participants who have been treated for HCV infection (referred to as treatment-experienced participants) who did not respond to previous therapy with interferon (IFN) and who did not discontinue previous anti-HCV therapy because of adverse events [AEs]) will be included in this study. Two blinded placebo-controlled groups (referred to as "cohorts") of treatment-naïve participants will be sequentially initiated TMC435 to ensure that a higher dose is only administered if the previous lower dose is found safe and tolerable. The first group (Cohort 1) of treatment-naïve participants will receive low-doses of TMC435 or placebo for 7 days followed by 21 days of combined tritherapy with PegIFNa-2a and ribavirin OR participants will receive 28 days of tritherapy (TMC435 or placebo + PegIFNa-2a and ribavirin). After review of data from Cohort 1, a second group (Cohort 2) of treatment-naïve participants will be given higher doses of TMC435 or placebo in the same manner described for the first cohort. A third group (Cohort 3) of participants previously planned in the study will not be enrolled. After review of data from Cohort 2, a fourth group (Cohort 4) of treatment-experienced participants will be given 28 days of TMC435 (or placebo) as tritherapy with PegIFNa-2a and ribavirin to determine the maximum tolerated dose of TMC435. In addition, up to 10 HCV-infected individuals (who participated in study TMC435350-TiDP16-C101 (ClinicalTrials.gov registry number NCT00938899) will comprise Cohort 5 and will be given 28 days of TMC435 at a dose previously determined to be safe and efficacious as tritherapy with PegIFNa-2a and ribavirin. Blood samples will be taken from participants at protocol-specified time points to determine plasma concentrations of TMC435 and ribavirin and safety will be monitored throughout the study. Individuals will participate in this study for up 54 weeks (includes up to 6 weeks during the screening period followed by up to 4 weeks of study treatment with TMC435 (or placebo) and up to a maximum of 44 weeks of treatment with PegIFNa-2a and ribavirin.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 10
| Arm | Type | Receives |
|---|---|---|
| TMC435 25 mg (Cohort 1/Panel A and B) | Experimental | Drug: TMC435, Drug: Peginterferon (PegIFNα-2a), Drug: RibavirinTreatment-naïve participants received TMC435 25 mg once daily for 7 days followed by TMC435 25 mg once daily coadministered with peginterferon alpha-2a (PegIFNα-2a) (P) and ribavirin (R) for 21 days (Panel A) OR TMC435 25 mg once daily coadministered with PR for 28 days (Panel B). |
| TMC435 75mg (Cohort 1/Panel A and B) | Experimental | Drug: TMC435, Drug: Peginterferon (PegIFNα-2a), Drug: RibavirinTreatment-naïve participants received TMC435 75 mg once daily for 7 days followed by TMC435 75 mg once daily for 21 days with PegIFNα-2a (P) and ribavirin (R) OR TMC435 75 mg once daily coadministered with PR for 28 days (Panel B). |
| Placebo (Cohort 1/Panel A and B) | Placebo comparator | Drug: Placebo, Drug: Peginterferon (PegIFNα-2a), Drug: RibavirinTreatment-naïve participants received placebo (identical in appearance to TMC435 25/75 mg) once daily for 7 days followed by placebo once daily coadministered with PegIFNα-2a (P) and ribavirin (R) for 21 days (Panel A) OR and Placebo once daily coadministered with PR for 28 days (Panel B). |
| TMC435 200 mg (Cohort 2, Panel A and B) | Experimental | Drug: TMC435, Drug: Peginterferon (PegIFNα-2a), Drug: RibavirinTreatment-naïve participants received TMC435 200 mg once daily for 7 days followed by TMC435 200 mg once daily coadministered with PegIFNα-2a (P) and ribavirin (R) for 21 days (Panel A) OR TMC435 200 mg once daily coadministered with PR for 28 days (Panel B). |
| Placebo (Cohort 2/Panel A and B) | Placebo comparator | Drug: Placebo, Drug: Peginterferon (PegIFNα-2a), Drug: RibavirinTreatment-naïve participants received placebo (identical in appearance to TMC435 200 mg) once daily for 7 days followed by placebo once daily coadministered with PegIFNα-2a (P) and ribavirin (R) for 21 days (Panel A) OR placebo once daily coadministered with PR for 28 days (Panel B). |
| TMC435 75 mg (Cohort 4/Panel C) | Experimental | Drug: TMC435, Drug: Peginterferon (PegIFNα-2a), Drug: RibavirinTreatment-experienced non-responders received TMC435 75 mg once daily coadministered with PegIFNα-2a and ribavirin for 28 days. |
| TMC435 150 mg (Cohort 4/Panel C) | Experimental | Drug: TMC435, Drug: Peginterferon (PegIFNα-2a), Drug: RibavirinTreatment-experienced non-responders received TMC435 150 mg once daily coadministered with PegIFNα-2a and ribavirin for 28 days. |
| TMC435 200 mg (Cohort 4/Panel C) | Experimental | Drug: TMC435, Drug: Peginterferon (PegIFNα-2a), Drug: RibavirinTreatment-experienced non-responders received TMC435 200 mg once daily coadministered with PegIFNα-2a and ribavirin for 28 days. |
| Placebo (Cohort 4/Panel C) | Placebo comparator | Drug: Placebo, Drug: Peginterferon (PegIFNα-2a), Drug: RibavirinTreatment-experienced non-responders received placebo once daily coadministered with PegIFNα-2a and ribavirin for 28 days. |
| TMC435 200 mg (Cohort 5/Panel D) | Experimental | Drug: TMC435, Drug: Peginterferon (PegIFNα-2a), Drug: RibavirinTreatment-experienced relapsers received TMC435 200 mg once daily coadministered with PegIFNα-2a and ribavirin for 28 days. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TMC435TMC435 25 mg, 75 mg, 150 mg, or 200 mg capsules taken orally (by mouth) once daily for 21 or 28 days. | Drug | TMC435 150 mg (Cohort 4/Panel C), TMC435 200 mg (Cohort 2, Panel A and B), TMC435 200 mg (Cohort 4/Panel C), TMC435 200 mg (Cohort 5/Panel D), TMC435 25 mg (Cohort 1/Panel A and B), TMC435 75 mg (Cohort 4/Panel C), TMC435 75mg (Cohort 1/Panel A and B) |
| PlaceboPlacebo capsules identical in appearance to TMC435 capsules taken orally (by mouth) once daily for 28 days. | Drug | Placebo (Cohort 1/Panel A and B), Placebo (Cohort 2/Panel A and B), Placebo (Cohort 4/Panel C) |
| Peginterferon (PegIFNα-2a)Also: PEGASYSOne subcutaneous (under the skin) injection containing 0.5 mL solution with 180 mcg PegIFNα-2a on Days 1, 8, 15, and 22 | Drug | Placebo (Cohort 1/Panel A and B), Placebo (Cohort 2/Panel A and B), Placebo (Cohort 4/Panel C), TMC435 150 mg (Cohort 4/Panel C), TMC435 200 mg (Cohort 2, Panel A and B), TMC435 200 mg (Cohort 4/Panel C), TMC435 200 mg (Cohort 5/Panel D), TMC435 25 mg (Cohort 1/Panel A and B), TMC435 75 mg (Cohort 4/Panel C), TMC435 75mg (Cohort 1/Panel A and B) |
| RibavirinAlso: COPEGUS200-mg tablets of ribavirin (body-weight adjusted dose) taken orally (by mouth) twice daily for 21 or 28 days in Cohorts 1 and 2 and for 28 days in Cohorts 4 and 5. | Drug | Placebo (Cohort 1/Panel A and B), Placebo (Cohort 2/Panel A and B), Placebo (Cohort 4/Panel C), TMC435 150 mg (Cohort 4/Panel C), TMC435 200 mg (Cohort 2, Panel A and B), TMC435 200 mg (Cohort 4/Panel C), TMC435 200 mg (Cohort 5/Panel D), TMC435 25 mg (Cohort 1/Panel A and B), TMC435 75 mg (Cohort 4/Panel C), TMC435 75mg (Cohort 1/Panel A and B) |
Primary outcome
Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) at Week 4 in Treatment-Naïve HCV-Infected Participants (Cohort 1 and 2, Panel A)
Time frame: Week 4
The table below shows the change from Baseline in plasma levels of HCV RNA at Week 4 following treatment with TMC435 or placebo as for 7 days followed by TMC435 or placebo coadministered with ribavirin for 21 days + peginterferon alpha-2a (PegIFNα-2a) on Days 1, 8, 15, and 22 in treatment-naïve HCV-infected participants. (A treatment-naive participant is someone who has never taken drugs for their HCV infection).
Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) at Week 4 in Treatment-Naïve HCV-Infected Participants (Cohort 1 and 2, Panel B)
Time frame: Week 4
The table below shows the change from Baseline in plasma levels of HCV RNA at Week 4 following treatment with TMC435 or placebo coadministered with ribavirin for 28 days + peginterferon alpha-2a (PegIFNα-2a) on Days 1, 8, 15, and 22 in treatment-naïve HCV-infected participants. (A treatment-naive participant is someone who has never taken drugs for their HCV infection).
Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) at Week 4 in Treatment-Experienced HCV-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D)
Time frame: Week 4
The table below shows the change from Baseline in plasma levels of HCV RNA at Week 4 following treatment with TMC435 or placebo coadministered with ribavirin for 28 days + peginterferon alpha-2a (PegIFNα-2a) on Days 1, 8, 15, and 22 in treatment-experienced participants considered non-responders (defined as participants who achieved less than a 2 log10 IU/mL decline from baseline in plasma HCV RNA levels after 12 weeks of previous interferon [IFN]-based therapy [pegylated or non-pegylated]) or relapsers (defined as a participant with undetectable plasma HCV RNA at the end of treatment of previous IFN-based therapy and subsequent confirmed detectable plasma HCV RNA levels during follow-up).
25 secondary outcomes
Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) on Day 7 in Treatment-Naïve HCV-Infected Participants (Cohort 1 and 2, Panel A)
Time frame: Day 7
Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) on Day 7 in Treatment-Naïve HCV-Infected Participants (Cohort 1 and 2, Panel B)
Time frame: Day 7
Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) on Day 7 in Treatment-Experienced HCV-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D)
Time frame: Day 7
Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A)
Time frame: Day 2 or 3, Day 7, and Day 28
Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B)
Time frame: Day 2 or 3, Day 7, and Day 28
Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D)
Time frame: Day 2 or 3, Day 7, and Day 28
Virologic Response Parameters in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined)
Time frame: Week 4 (RVR), Week 12 (EVR, cEVR, and partial response), and Week 4 and 12 (eRVR)
Virologic Response Parameters Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D)
Time frame: Week 4 (RVR), Week 12 (EVR, cEVR, and partial response), and Week 4 and 12 (eRVR)
Initial Suboptimal Responses Following Treatment With TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A)
Time frame: Day 2 or 3
Initial Suboptimal Responses Following Treatment With TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B)
Time frame: Day 2 or 3
Initial Suboptimal Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D)
Time frame: Day 2 or 3
Viral Breakthrough in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1, Panel A and B)
Time frame: 4 Weeks (Wks), 44 Wks, and 48 Wks
Viral Breakthrough in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D)
Time frame: 4 Weeks (Wks), 44 Wks, and 48 Wks
Viral Relapse in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined)
Time frame: Up to Week 72
Viral Relapse in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D)
Time frame: Up to Week 72
Sustained Virologic Response (SVR) in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined)
Time frame: SVR4 (Week 52), SVR8 (Week 56), SVR12 (Week 60), and SVR24 (Week 72)
Sustained Virologic Response (SVR) in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D)
Time frame: SVR4 (Week 52), SVR8 (Week 56), SVR12 (Week 60), and SVR24 (Week 72)
Maximum Plasma Concentration (Cmax) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B)
Time frame: Days 1 and 28 (predose and 0.5, 1, 2, 4, 6, 8, and 10 hours postdose)
Maximum Plasma Concentration (Cmax) of TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D)
Time frame: Days 1 and 28 (predose and 0.5, 1, 2, 4, 6, 8, and 10 hours postdose)
Predose Plasma Concentration (C0h) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B)
Time frame: Day 2 (predose) and Day 28 (predose and 0.5, 1, 2, 4, 6, 8, and 10 hours postdose)
Predose Plasma Concentration (C0h) of TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D)
Time frame: Day 2 (predose) and Day 28 (predose and 0.5, 1, 2, 4, 6, 8, and 10 hours postdose)
Average Steady-state Plasma Concentration (Css,av) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B)
Time frame: Day 7 (predose); Day 28 (predose and 0.5, 1, 2, 4, 6, 8, and 10 hours postdose) (Panel A, Cohorts 1 and 2) and Day 28 (predose and 0.5, 1, 2, 4, 6, 8, and 10 hours postdose) (Panel B, Cohorts 1 and 2)
Average Steady-state Plasma Concentration (Css,av) of TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D)
Time frame: Day 28 (predose and 0.5, 1, 2, 4, 6, 8, and 10 hours postdose)
Area Under the Plasma Concentration-time Curve From the Time of Administration to 24 Hours After Dosing (AUC24h) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B)
Time frame: Days 1 and 28 (predose and 0.5, 1, 2, 4, 6, 8, and 10 hours postdose)
Area Under the Plasma Concentration-time Curve From the Time of Administration to 24 Hours After Dosing (AUC24h) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D)
Time frame: Days 1 and 28 (predose and 0.5, 1, 2, 4, 6, 8, and 10 hours postdose)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 May 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38587329Benguigui L, Le Gouzouguec S, Balanca B, Ristovski M, Putet G, Butin M, Guillois B, Beissel A. A Customizable Digital Cognitive Aid for Neonatal Resuscitation: A Simulation-Based Randomized Controlled Trial. Simul Healthc. 2024 Oct 1;19(5):302-308. doi: 10.1097/SIH.0000000000000790. Epub 2024 Apr 8.
- Derived from this study: PubMed 22885330Lenz O, de Bruijne J, Vijgen L, Verbinnen T, Weegink C, Van Marck H, Vandenbroucke I, Peeters M, Simmen K, Fanning G, Verloes R, Picchio G, Reesink H. Efficacy of re-treatment with TMC435 as combination therapy in hepatitis C virus-infected patients following TMC435 monotherapy. Gastroenterology. 2012 Nov;143(5):1176-1178.e6. doi: 10.1053/j.gastro.2012.07.117. Epub 2012 Aug 8.
- Derived from this study: PubMed 22024518Manns M, Reesink H, Berg T, Dusheiko G, Flisiak R, Marcellin P, Moreno C, Lenz O, Meyvisch P, Peeters M, Sekar V, Simmen K, Verloes R. Rapid viral response of once-daily TMC435 plus pegylated interferon/ribavirin in hepatitis C genotype-1 patients: a randomized trial. Antivir Ther. 2011;16(7):1021-33. doi: 10.3851/IMP1894.
Related trials for Hepatitis C, Chronic
RecruitingObservational study
Evaluation of Patients With Liver Disease
Hepatitis D, Hepatitis C
Active, not recruitingPhase 4
People With CHC Who Achieved a Sustained Virological Response Following Therapy With Direct Acting Antiviral Agents
Diabetes Mellitus, Hepatitis C, Chronic
RecruitingObservational study
"Constitution of a Biological Collection to Establish Preclinical Translational Models for the Study of Tumors and Chronic Liver Diseases".
Chronic Liver Disease and Cirrhosis, Liver Cancer
Active, not recruitingPhase 4
Sofosbuvir/Velpatasvir Treatment of Chronic Hepatitis C During Pregnancy
Hepatitis C, Chronic, Pregnancy; Infection
Enrolling by invitationObservational study
Comparative Autoantibody and Immunologic Cell Marker Study
Autoimmune Diseases, Lupus Erythematosus, Systemic
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tibotec Pharmaceuticals, Ireland Clinical Trial study director
Tibotec Pharmaceuticals, Ireland
24 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing TMC435, Peginterferon (PegIFNα-2a) and Ribavirin in people with Hepatitis C, Chronic, run by Tibotec Pharmaceuticals, Ireland at 24 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 May 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 24 sites in Germany, France, Belgium, Poland, United Kingdom and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Feb 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) at Week 4 in Treatment-Naïve HCV-Infected Participants (Cohort 1 and 2, Panel A) (time frame: Week 4). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00561353, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 May 2014.