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    Clinical Trial Results:
    A Phase III open-label study to evaluate the safety, tolerability and efficacy of TMC435 plus PegIFNα-2a (Pegasys®) and ribavirin (Copegus®) triple therapy in chronic hepatitis C genotype-1 infected subjects who are co-infected with Human Immunodeficiency Virus type 1 (HIV-1).

    Due to a system error, the data reported in v1 is not correct and has been removed from public view.
    Summary
    EudraCT number
    2010-021337-31
    Trial protocol
    GB   ES   PT  
    Global end of trial date
    28 Aug 2013

    Results information
    Results version number
    v2(current)
    This version publication date
    30 Jun 2016
    First version publication date
    31 Jul 2015
    Other versions
    v1 (removed from public view)
    Version creation reason
    • Correction of full data set
    Review of data

    Trial information

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    Trial identification
    Sponsor protocol code
    TMC435-TiDP16-C212
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT01479868
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Janssen Sciences Ireland
    Sponsor organisation address
    Eastgate Village, Eastgate, Little Island, Co. Cork, Ireland,
    Public contact
    Clinical Registry Group, Janssen Sciences Ireland, 353 21 4673500, ClinicalTrialsEU@its.jnj.com
    Scientific contact
    Clinical Registry Group, Janssen Sciences Ireland, 353 21 4673500, ClinicalTrialsEU@its.jnj.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    28 Aug 2013
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    28 Aug 2013
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the safety and tolerability of TMC435 plus pegylated interferon alpha-2a (PegIFNα- 2a) and ribavirin (RBV) triple therapy in hepatitis C virus (HCV) genotype-1 infected participants, co-infected with human immunodeficiency virus- 1 (HIV-1). To evaluate the proportion of participants with sustained virologic response (SVR) 12 weeks after the planned end of treatment (SVR12).
    Protection of trial subjects
    Safety and tolerability were evaluated throughout the study by monitoring of adverse events (AEs), Performing laboratory tests, measurement of vital signs, electrocardiogram (ECG) and performing physical examinations throughout the study.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    19 Sep 2011
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Spain: 11
    Country: Number of subjects enrolled
    United Kingdom: 9
    Country: Number of subjects enrolled
    United States: 41
    Country: Number of subjects enrolled
    Canada: 8
    Country: Number of subjects enrolled
    France: 8
    Country: Number of subjects enrolled
    Germany: 17
    Country: Number of subjects enrolled
    Portugal: 12
    Worldwide total number of subjects
    106
    EEA total number of subjects
    57
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    104
    From 65 to 84 years
    2
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    A total of 160 participants were screened, 107 were enrolled of whom 106 participants received at least 1 dose of study drug.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Non-randomised - controlled
    Blinding used
    Not blinded

    Arms
    Arm title
    TMC435 150mg 12Wks PR24/48
    Arm description
    Participants On HAART (n=93) and Not on HAART (n=13) were given TMC435 150 mg once daily plus peginterferon alfa-2a (PegIFN alfa-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alfa-2a (P) and RBV (R) until Week 24/48 (PR24/48). Treatment was to be stopped at Week 24 for HCV treatment-naïve and prior HCV relapsers who met the response guided therapy criteria, and who did not have cirrhosis. All prior HCV non-responders (null and partial), Participants with cirrhosis, and HCV treatment-naïve and prior HCV relapsers who did not meet the response guided therapy criteria had a 48-week treatment period.
    Arm type
    Experimental

    Investigational medicinal product name
    JNJ-38733214-AAA - capsule , hard - 150mg
    Investigational medicinal product code
    TMC435
    Other name
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    Participants were administered JNJ-38733214-AAA - capsule , hard 150 mg orally, once daily.

    Investigational medicinal product name
    Pegasys
    Investigational medicinal product code
    Other name
    PEGINTERFERON ALFA-2A
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants were administered PEGINTERFERON ALFA-2A (PegIFNα-2a) 180 microgram(s)/millilitre (µg/ml) once weekly as subcutaneous injection of 0.5 mL.

    Investigational medicinal product name
    Copegus
    Investigational medicinal product code
    Other name
    Ribavirin
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants were administered Ribavirin 1000 or 1200 milligrams (mg) orally, twice a day.

    Number of subjects in period 1
    TMC435 150mg 12Wks PR24/48
    Started
    106
    Completed
    97
    Not completed
    9
         Sponsor's decision
    1
         Participant initiated new HCV therapy
    1
         Adverse event, serious fatal
    1
         Participant non-compliant
    1
         Consent withdrawn by subject
    1
         Lost to follow-up
    4

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    TMC435 150mg 12Wks PR24/48
    Reporting group description
    Participants On HAART (n=93) and Not on HAART (n=13) were given TMC435 150 mg once daily plus peginterferon alfa-2a (PegIFN alfa-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alfa-2a (P) and RBV (R) until Week 24/48 (PR24/48). Treatment was to be stopped at Week 24 for HCV treatment-naïve and prior HCV relapsers who met the response guided therapy criteria, and who did not have cirrhosis. All prior HCV non-responders (null and partial), Participants with cirrhosis, and HCV treatment-naïve and prior HCV relapsers who did not meet the response guided therapy criteria had a 48-week treatment period.

    Reporting group values
    TMC435 150mg 12Wks PR24/48 Total
    Number of subjects
    106 106
    Title for AgeCategorical
    Units: subjects
        Children (2-11 years)
    0 0
        Adolescents (12-17 years)
    0 0
        Adults (18-64 years)
    104 104
        From 65 to 84 years
    2 2
        85 years and over
    0 0
    Title for AgeContinuous
    Units: years
        median (full range (min-max))
    48 (27 to 67) -
    Title for Gender
    Units: subjects
        Female
    16 16
        Male
    90 90

    End points

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    End points reporting groups
    Reporting group title
    TMC435 150mg 12Wks PR24/48
    Reporting group description
    Participants On HAART (n=93) and Not on HAART (n=13) were given TMC435 150 mg once daily plus peginterferon alfa-2a (PegIFN alfa-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alfa-2a (P) and RBV (R) until Week 24/48 (PR24/48). Treatment was to be stopped at Week 24 for HCV treatment-naïve and prior HCV relapsers who met the response guided therapy criteria, and who did not have cirrhosis. All prior HCV non-responders (null and partial), Participants with cirrhosis, and HCV treatment-naïve and prior HCV relapsers who did not meet the response guided therapy criteria had a 48-week treatment period.

    Primary: Percentage of Participants With Sustained Virologic Response at Week 12 (SVR 12)

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    End point title
    Percentage of Participants With Sustained Virologic Response at Week 12 (SVR 12) [1]
    End point description
    The SVR 12 was defined as hepatitis C virus (HCV) ribonucleic acid (RNA) levels less than (<) 25 international unit per millilitre (IU/mL) undetectable at the planned end of treatment (EOT), and HCV RNA levels <25 IU/mL undetectable or HCV RNA levels <25 IU/mL detectable at 12 Weeks after end of treatment.
    End point type
    Primary
    End point timeframe
    12 weeks after planned end of treatment (Week 24 or 48)
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive statistics were done, no inferential statistical analyses were performed
    End point values
    TMC435 150mg 12Wks PR24/48
    Number of subjects analysed
    106
    Units: Percentage of Participants
        number (not applicable)
    73.6
    No statistical analyses for this end point

    Secondary: Percentage of Participants With Sustained Virologic Response at Week 24 (SVR 24)

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    End point title
    Percentage of Participants With Sustained Virologic Response at Week 24 (SVR 24)
    End point description
    The SVR 24 was defined as hepatitis C virus (HCV) ribonucleic acid (RNA) levels less than (<) 25 international unit per millilitre (IU/mL) undetectable at the planned end of treatment (EOT), and HCV RNA levels <25 IU/mL undetectable or HCV RNA levels <25 IU/mL detectable at 24 weeks after end of treatment.
    End point type
    Secondary
    End point timeframe
    24 weeks after planned end of treatment (Week 24 or 48).
    End point values
    TMC435 150mg 12Wks PR24/48
    Number of subjects analysed
    106
    Units: Percentage of Participants
        number (not applicable)
    72.6
    No statistical analyses for this end point

    Secondary: On treatment data for percentage of Participants With Hepatitis C Virus Ribonucleic Acid (HCV-RNA) Less Than (<) 25 International Units (IU/mL) Undetectable or Detectable/Undetectable

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    End point title
    On treatment data for percentage of Participants With Hepatitis C Virus Ribonucleic Acid (HCV-RNA) Less Than (<) 25 International Units (IU/mL) Undetectable or Detectable/Undetectable
    End point description
    Percentage of participants with HCV RNA less than (<) 25 IU/mL undetectable (undet.) or detectable (det.)/undetectable at specific time points were observed. ITT population included all participants who had at least 1 dose of study drug. Here, "N" (number of participants analysed) is the number of participants analysed for this outcome measure, "n" is the number of participants analysed for this outcome measure at specific time points.
    End point type
    Secondary
    End point timeframe
    Week 4, 12, 24, 36, and 48
    End point values
    TMC435 150mg 12Wks PR24/48
    Number of subjects analysed
    105
    Units: Percentage of Participants
    number (not applicable)
        Week 4: < 25 IU/mL HCV-RNA undet. (n=105)
    65.7
        Week 4:< 25 IU/mL HCV-RNA det./undet. (n=105)
    88.6
        Week 12:< 25 IU/mL HCV-RNA undet. (n=97)
    94.8
        Week 12:< 25 IU/mL HCV-RNA det./undet. (n=97)
    97.9
        Week 24:< 25 IU/mL HCV-RNA undet. (n=90)
    90
        Week 24:< 25 IU/mL HCV-RNA det./undet. (n=90)
    93.3
        Week 48:< 25 IU/mL HCV-RNA undet. (n=28)
    100
        Week 48:< 25 IU/mL HCV-RNA det./undet. (n=28)
    100
    No statistical analyses for this end point

    Secondary: Percentage of Participants With On-treatment Failure

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    End point title
    Percentage of Participants With On-treatment Failure
    End point description
    Participants were considered as an on-treatment failure if, at actual end of treatment (EOT), there was confirmed detectable HCV RNA levels.
    End point type
    Secondary
    End point timeframe
    Actual EOT (Week 24 or Week 48 or Early Withdrawal)
    End point values
    TMC435 150mg 12Wks PR24/48
    Number of subjects analysed
    106
    Units: Percentage of Participants
        number (not applicable)
    17
    No statistical analyses for this end point

    Secondary: Percentage of Participants With Viral Breakthrough

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    End point title
    Percentage of Participants With Viral Breakthrough
    End point description
    Confirmed increase of more than 1 log10 IU per mL in HCV RNA level from the lowest level reached, or a confirmed HCV RNA level of more than 100 IU per mL in participants whose HCV RNA levels had previously been below the limit of quantification (less than 25 IU per mL detectable) or undetectable (less than 25 IU per mL undetectable), while on study therapy.
    End point type
    Secondary
    End point timeframe
    Up to Actual EOT (Week 24 or Week 48 or Early Withdrawal)
    End point values
    TMC435 150mg 12Wks PR24/48
    Number of subjects analysed
    105
    Units: Percentage of Participants
        number (not applicable)
    11.4
    No statistical analyses for this end point

    Secondary: Percentage of Participants With Viral Relapse

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    End point title
    Percentage of Participants With Viral Relapse
    End point description
    Participants were considered to have a viral relapse when, at actual end of treatment, HCV RNA levels were less than 25 IU per mL undetectable; and during the follow-up period, HCV RNA levels were more than or equal to 25 IU per mL. The incidence of viral relapse is only calculated for subjects with undetectable (or unconfirmed detectable) HCV RNA levels at actual end of treatment, and with at least one follow-up HCV RNA measurement.
    End point type
    Secondary
    End point timeframe
    Actual EOT (Week 24 or Week 48 or Early Withdrawal) up to end of follow-up period
    End point values
    TMC435 150mg 12Wks PR24/48
    Number of subjects analysed
    87
    Units: Percentage of Participants
        number (not applicable)
    10.3
    No statistical analyses for this end point

    Secondary: Percentage of Participants With Normalized Alanine Aminotransferase Levels

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    End point title
    Percentage of Participants With Normalized Alanine Aminotransferase Levels
    End point description
    Participants with normalized alanine aminotransferase levels observed whose alanine aminotransferase levels were out of normal range at Baseline.
    End point type
    Secondary
    End point timeframe
    Baseline up to Week 72
    End point values
    TMC435 150mg 12Wks PR24/48
    Number of subjects analysed
    65
    Units: Percentage of Participants
        number (not applicable)
    81.5
    No statistical analyses for this end point

    Secondary: Percentage of Human Immunodeficiency Virus (HIV) Participants With Virologic Failure

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    End point title
    Percentage of Human Immunodeficiency Virus (HIV) Participants With Virologic Failure
    End point description
    Participants had confirmed HIV virologic failure if HIV viral load values were greater than or equal to 50 or 200 copies/mL among those who previously had less than 50 copies/mL for participants on HAART (n=93).
    End point type
    Secondary
    End point timeframe
    Baseline to Week 72.
    End point values
    TMC435 150mg 12Wks PR24/48
    Number of subjects analysed
    93
    Units: Percentage of Participants
    number (not applicable)
        Greater than or equal to 50 copies/mL
    5.4
        Greater than or equal to 200 copies/mL
    2.2
    No statistical analyses for this end point

    Secondary: Mean Change From Baseline in Log10 Plasma Human Immunodeficiency Virus (HIV) Viral Load

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    End point title
    Mean Change From Baseline in Log10 Plasma Human Immunodeficiency Virus (HIV) Viral Load
    End point description
    Participants who received potent anti-HIV treatment with a combination of more than 3 antiretroviral therapies to reduce HIV RNA viral load to undetectable levels were analyzed. Here "n" signifies participants evaluable for this measure at specified time point.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1), Week 2, 4, 8, 12, 16, 20, 24, 28, 36, 42, 48, 52, 60 and 72
    End point values
    TMC435 150mg 12Wks PR24/48
    Number of subjects analysed
    93
    Units: copies per milliliter
    arithmetic mean (standard deviation)
        Baseline (n=93)
    1.3726 ± 0.25796
        Change at Week 2 (n=91)
    -0.0724 ± 0.23857
        Change at Week 4 (n=93)
    -0.0704 ± 0.25817
        Change at Week 8 (n=92)
    -0.0442 ± 0.40974
        Change at Week 12 (n=90)
    -0.0655 ± 0.3051
        Change at Week 16 (n=88)
    -0.0829 ± 0.23986
        Change at Week 20 (n=86)
    -0.0847 ± 0.25111
        Change at Week 24 (n=88)
    -0.0689 ± 0.24785
        Change at Week 28 (n=82)
    -0.0564 ± 0.26319
        Change at Week 36 (n=85)
    0.0004 ± 0.24395
        Change at Week 42 (n=35)
    -0.0623 ± 0.29365
        Change at Week 48 (n=79)
    -0.0041 ± 0.36177
        Change at Week 52 (n=36)
    0.0011 ± 0.20767
        Change at Week 60 (n=40)
    -0.0184 ± 0.2094
        Change at Week 72 (n=38)
    -0.0265 ± 0.18323
        Change at End of study (n=93)
    0.0099 ± 0.33435
    No statistical analyses for this end point

    Secondary: Mean Change From Baseline in CD4+ Cell Count

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    End point title
    Mean Change From Baseline in CD4+ Cell Count
    End point description
    Participants who received potent anti-HIV treatment with a combination of more than 3 antiretroviral therapies to reduce HIV RNA viral load to undetectable levels were analyzed. Here, "n" is the number of participants analysed for this outcome measure at specific time points for participants on HAART (n=93).
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1), Week 2, 4, 8, 12, 16, 20, 24, 28, 36, 42, 48, 52, 60 and 72
    End point values
    TMC435 150mg 12Wks PR24/48
    Number of subjects analysed
    93
    Units: cell counts per microliter
    arithmetic mean (standard deviation)
        Baseline (n=93)
    640.3 ± 243.11
        Change at Week 2 (n=89)
    -95 ± 190.34
        Change at Week 4 (n=91)
    -171.5 ± 170.67
        Change at Week 8 (n=92)
    -244.2 ± 185.04
        Change at Week 12 (n=91)
    -271.7 ± 194.49
        Change at Week 16 (n=88)
    -275.5 ± 183.96
        Change at Week 20 (n=84)
    -283.5 ± 175.27
        Change at Week 24 (n=89)
    -288.8 ± 202.31
        Change at Week 28 (n=82)
    -252.3 ± 203.45
        Change at Week 36 (n=83)
    -198.7 ± 225.62
        Change at Week 42 (n=33)
    -336.8 ± 240.64
        Change at Week 48 (n=77)
    -166.6 ± 248.25
        Change at Week 52 (n=35)
    -202.7 ± 222.89
        Change at Week 60 (n=40)
    -90.6 ± 189.74
        Change at Week 72 (n=38)
    -62.9 ± 175.61
        Change at End of Study (n=93)
    -51.1 ± 178.2
    No statistical analyses for this end point

    Secondary: Change From Baseline in CD4+ Cell Count in Percentage

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    End point title
    Change From Baseline in CD4+ Cell Count in Percentage
    End point description
    Participants who received potent anti-HIV treatment with a combination of more than 3 antiretroviral therapies to reduce HIV RNA viral load to undetectable levels were analysed. Here, "n" is the number of participants analysed for this outcome measure at specific time points for participants on HAART (n=93).
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1), Week 2, 4, 8, 12, 16, 20, 24, 28, 36, 42, 48, 52, 60 and 72
    End point values
    TMC435 150mg 12Wks PR24/48
    Number of subjects analysed
    93
    Units: percentage of lymphocyte
    arithmetic mean (standard deviation)
        Baseline (n=93)
    31.65 ± 8.39
        Change at Week 2 (n=89)
    0.42 ± 6.49
        Change at Week 4 (n=91)
    2.5 ± 5.943
        Change at Week 8 (n=92)
    3.85 ± 5.93
        Change at Week 12 (n=91)
    3.93 ± 6.264
        Change at Week 16 (n=88)
    5.47 ± 6.301
        Change at Week 20 (n=84)
    5.27 ± 6.961
        Change at Week 24 (n=89)
    5.5 ± 7.029
        Change at Week 28 (n=82)
    3.79 ± 6.759
        Change at Week 36 (n=83)
    2.75 ± 6.492
        Change at Week 42 (n=33)
    6.41 ± 6.213
        Change at Week 48 (n=77)
    2.09 ± 7.356
        Change at Week 52 (n=35)
    3.26 ± 6.838
        Change at Week 60 (n=40)
    0.25 ± 5.296
        Change at Week 72 (n=38)
    0.7 ± 4.406
        Change at End of study (n=93)
    0.13 ± 6.169
    No statistical analyses for this end point

    Secondary: Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)

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    End point title
    Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
    End point description
    An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between administration of study drug and up to Day 126 that were absent before treatment or that worsened relative to pre-treatment state.
    End point type
    Secondary
    End point timeframe
    Baseline up to End of Treatment (EOT: Week 24 or Week 48 or Early Withdrawal) +4 weeks.
    End point values
    TMC435 150mg 12Wks PR24/48
    Number of subjects analysed
    106
    Units: Participants
    number (not applicable)
        TEAEs
    102
        TESAEs
    6
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Baseline up to End of Treatment (EOT: Week 24 or Week 48 or Early Withdrawal) +4 weeks.
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    14.1
    Reporting groups
    Reporting group title
    TMC435 150mg 12Wks PR24/48
    Reporting group description
    Participants On HAART (n=93) and Not on HAART (n=13) were given TMC435 150 mg once daily plus peginterferon alfa-2a (PegIFN alfa-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alfa-2a (P) and RBV (R) until Week 24/48 (PR24/48). Treatment was to be stopped at Week 24 for HCV treatment-naïve and prior HCV relapsers who met the response guided therapy criteria, and who did not have cirrhosis. All prior HCV non-responders (null and partial), subjects with cirrhosis, and HCV treatment-naïve and prior HCV relapsers who did not meet the response guided therapy criteria had a 48-week treatment period.

    Serious adverse events
    TMC435 150mg 12Wks PR24/48
    Total subjects affected by serious adverse events
         subjects affected / exposed
    11 / 106 (10.38%)
         number of deaths (all causes)
    1
         number of deaths resulting from adverse events
    Injury, poisoning and procedural complications
    Thoracic vertebral fracture
         subjects affected / exposed
    1 / 106 (0.94%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Investigations
    Aspartate aminotransferase increased
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 106 (0.94%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cardiac disorders
    Angina pectoris
         subjects affected / exposed
    1 / 106 (0.94%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 106 (0.94%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    2 / 106 (1.89%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Pneumothorax
         subjects affected / exposed
    1 / 106 (0.94%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    General disorders and administration site conditions
    General physical health deterioration
         subjects affected / exposed
    1 / 106 (0.94%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Psychiatric disorders
    Mental status changes
         subjects affected / exposed
    1 / 106 (0.94%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Psychotic disorder
         subjects affected / exposed
    1 / 106 (0.94%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal disorders
    Anal haemorrhage
         subjects affected / exposed
    1 / 106 (0.94%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Colitis
         subjects affected / exposed
    1 / 106 (0.94%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hepatobiliary disorders
    Hyperbilirubinaemia
         subjects affected / exposed
    1 / 106 (0.94%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Musculoskeletal and connective tissue disorders
    Cervical spinal stenosis
         subjects affected / exposed
    1 / 106 (0.94%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Intervertebral disc protrusion
         subjects affected / exposed
    1 / 106 (0.94%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Metabolism and nutrition disorders
    Malnutrition
         subjects affected / exposed
    1 / 106 (0.94%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Infections and infestations
    Catheter site infection
         subjects affected / exposed
    1 / 106 (0.94%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    TMC435 150mg 12Wks PR24/48
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    103 / 106 (97.17%)
    Investigations
    Weight decreased
         subjects affected / exposed
    13 / 106 (12.26%)
         occurrences all number
    13
    Neutrophil count decreased
         subjects affected / exposed
    6 / 106 (5.66%)
         occurrences all number
    8
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    11 / 106 (10.38%)
         occurrences all number
    13
    Dyspnoea
         subjects affected / exposed
    10 / 106 (9.43%)
         occurrences all number
    10
    Oropharyngeal pain
         subjects affected / exposed
    9 / 106 (8.49%)
         occurrences all number
    9
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    30 / 106 (28.30%)
         occurrences all number
    47
    Neutropenia
         subjects affected / exposed
    33 / 106 (31.13%)
         occurrences all number
    76
    Thrombocytopenia
         subjects affected / exposed
    6 / 106 (5.66%)
         occurrences all number
    14
    Nervous system disorders
    Headache
         subjects affected / exposed
    35 / 106 (33.02%)
         occurrences all number
    48
    Dizziness
         subjects affected / exposed
    13 / 106 (12.26%)
         occurrences all number
    13
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    48 / 106 (45.28%)
         occurrences all number
    57
    Influenza like illness
         subjects affected / exposed
    25 / 106 (23.58%)
         occurrences all number
    37
    Asthenia
         subjects affected / exposed
    24 / 106 (22.64%)
         occurrences all number
    29
    Pyrexia
         subjects affected / exposed
    12 / 106 (11.32%)
         occurrences all number
    12
    Chills
         subjects affected / exposed
    9 / 106 (8.49%)
         occurrences all number
    10
    Injection site erythema
         subjects affected / exposed
    6 / 106 (5.66%)
         occurrences all number
    6
    Injection site reaction
         subjects affected / exposed
    8 / 106 (7.55%)
         occurrences all number
    8
    Pain
         subjects affected / exposed
    7 / 106 (6.60%)
         occurrences all number
    9
    Gastrointestinal disorders
    Vomiting
         subjects affected / exposed
    14 / 106 (13.21%)
         occurrences all number
    17
    Nausea
         subjects affected / exposed
    31 / 106 (29.25%)
         occurrences all number
    34
    Diarrhoea
         subjects affected / exposed
    25 / 106 (23.58%)
         occurrences all number
    33
    Constipation
         subjects affected / exposed
    12 / 106 (11.32%)
         occurrences all number
    13
    Psychiatric disorders
    Depression
         subjects affected / exposed
    19 / 106 (17.92%)
         occurrences all number
    20
    Mood altered
         subjects affected / exposed
    20 / 106 (18.87%)
         occurrences all number
    26
    Insomnia
         subjects affected / exposed
    27 / 106 (25.47%)
         occurrences all number
    27
    Anxiety
         subjects affected / exposed
    13 / 106 (12.26%)
         occurrences all number
    14
    Sleep disorder
         subjects affected / exposed
    6 / 106 (5.66%)
         occurrences all number
    6
    Skin and subcutaneous tissue disorders
    Pruritus
         subjects affected / exposed
    19 / 106 (17.92%)
         occurrences all number
    21
    Eczema
         subjects affected / exposed
    8 / 106 (7.55%)
         occurrences all number
    8
    Dry skin
         subjects affected / exposed
    16 / 106 (15.09%)
         occurrences all number
    17
    Alopecia
         subjects affected / exposed
    7 / 106 (6.60%)
         occurrences all number
    8
    Rash
         subjects affected / exposed
    7 / 106 (6.60%)
         occurrences all number
    7
    Musculoskeletal and connective tissue disorders
    Myalgia
         subjects affected / exposed
    17 / 106 (16.04%)
         occurrences all number
    17
    Back pain
         subjects affected / exposed
    8 / 106 (7.55%)
         occurrences all number
    8
    Arthralgia
         subjects affected / exposed
    15 / 106 (14.15%)
         occurrences all number
    16
    Pain in extremity
         subjects affected / exposed
    6 / 106 (5.66%)
         occurrences all number
    6
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    21 / 106 (19.81%)
         occurrences all number
    21
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    7 / 106 (6.60%)
         occurrences all number
    8
    Upper respiratory tract infection
         subjects affected / exposed
    7 / 106 (6.60%)
         occurrences all number
    8

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    19 Jan 2012
    The amendment was created to implement the changes to the protocol based on the feedback from the Health Authorities, mainly on primary efficacy endpoint for ongoing and future TMC435 Phase III trials could be changed from SVR24 to SVR12. SVR24 became a secondary endpoint.

    Interruptions (globally)

    Were there any global interruptions to the trial? No

    Limitations and caveats

    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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