Hepatitis C Virus Genotype-1
Conditions
Keywords
Hepatitis C virus genotype-1, Human immunodeficiency virus-type 1, HCV-1, HIV-1, TMC435, Pegylated interferon alpha-2a, PegIFNα-2a, Pegasys, Ribavirin, RBV, Copegus
Brief summary
The purpose of this study is to evaluate the safety and tolerability of TMC435 along with pegylated interferon alpha-2a (PegIFNα-2a) and ribavirin (RBV) triple therapy in hepatitis C virus genotype-1 infected subjects, co-infected with human immunodeficiency virus-type 1, and to evaluate the number of patients with sustained virologic response (SVR) at 12 weeks after the planned end of treatment.
Detailed description
This is an open-label (all the people know the identity of the intervention), single arm (study will be conducted in a single group) clinical study, to evaluate the safety, tolerability and efficacy of TMC435 along with pegylated interferon alpha-2a (PegIFNα-2a) and ribavirin (RBV) triple therapy in adult chronic hepatitis C (CHC) genotype-1 infected patients who are co-infected with human immunodeficiency virus-type 1 (HIV-1). The study consists of 3 phases, screening phase (Week -6), treatment phase, and a follow-up phase (up to 24 weeks). In the treatment phase, patients will be classified based on their experience with previous hepatitis C virus (HCV) treatment as follows: 1) HCV treatment-naive (patients who never received medication for the treatment of HCV); 2) prior HCV relapsers (patients who received at least 24 weeks of a PegIFNα-2a and RBV-based therapy and relapsed within 1 year after the last medication intake); and 3) prior HCV non-responders (can be further classified as, null responders: patients having at least 1 prior documented course of PegIFNα-2a and RBV therapy for at least 12 consecutive weeks; or partial responders: patients having at least 20 consecutive weeks which has not been discontinued due to intolerability to PegIFNα-2a and RBV therapy). All patients will receive TMC435 once daily along with PegIFNα-2a and RBV for 12 weeks. Patients who are continuing treatment only with PegIFNα-2a and RBV will follow until 24 or 48 weeks. Pharmacokinetics will be measured after collection of blood samples. Safety evaluations for adverse events, clinical laboratory tests, electrocardiogram, vital signs, physical examinations, and specific toxicities will be performed throughout the study. The total duration of treatment is approximately of 24 weeks.
Interventions
DRUGTMC435
TMC435 150 mg will be administered once daily for 12 weeks along with peginterferon alpha-2a and ribavirin.
Pegylated interferon alpha-2a 180 microgram will be administered as subcutaneous injection of 0.5 mL until 24 to 48 weeks.
DRUGRibavirin
Ribavirin 1000 or 1200 mg twice daily will be administered each day until 24 to 48 weeks.
Sponsors
Janssen R&D Ireland
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* A liver biopsy required within 3 years prior to screening unless the patient has a contraindication for a liver biopsy * Patients with bridging fibrosis or cirrhosis and without a liver biopsy result within 2 years prior screening must have an ultrasound taken within 2 months prior to the screening visit or during screening with no findings suspicious for hepatocellular carcinoma (HCC) * Genotype-1 hepatitis C virus (HCV) infection * Plasma HCV ribonucleic acid (RNA) of more than 10,000 IU per mL * Documented human immunodeficiency virus-type 1 (HIV-1) infection at least 6 months prior to screening
Exclusion criteria
* Patient showing evidence of hepatic decompensation (ie, history or current evidence of ascites, bleeding varices or hepatic encephalopathy, albumin serum concentration less than 3.3 gm per dL, prolonged prothrombin time \[PT\] expressed as international normalized ratio \[INR\] more than 1.5) * Any liver disease of non-HCV etiology * Co-infection with hepatitis B virus (hepatitis B surface antigen \[HBsAg\] positive) * An acute HIV-1 infection; or HIV-2 infection * Change in antiretroviral (ARV) regimen within the last 4 weeks prior screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Sustained Virologic Response at Week 12 (SVR 12) | 12 weeks after end of treatment (Week 24 or 48) | The SVR 12 was defined as hepatitis C virus (HCV) ribonucleic acid (RNA) levels less than (\<) 25 international unit per milliliter (IU/mL) undetectable at the actual 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Hepatitis C Virus Ribonucleic Acid (HCV-RNA) Less Than (<) 25 International Units (IU/mL) Undetectable or Detectable/Undetectable | Week 4, 12, 24, 36, and 48 | Percentage of participants with HCV RNA less than (\<) 25 IU/mL undetectable (undet.) or detectable (det.)/undetectable at specific time points were observed. |
| Percentage of Participants With On-treatment Failure | Week 1 to 48 | Participants were considered as an on-treatment failure if, at actual end of treatment (EOT), there was confirmed detectable HCV RNA levels. |
| Percentage of Participants With Viral Breakthrough | Week 1 to 48 | 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. |
| Percentage of Participants With Viral Relapse | Week 1 to 72 | 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. |
| Percentage of Participants With Normalized Alanine Aminotransferase Levels | Baseline up to Week 72 | Participants with normalized alanine aminotransferase levels observed whose alanine aminotransferase levels were out of range at Baseline. |
| Percentage of Participants With Sustained Virologic Response at Week 24 (SVR 24) | 24 weeks after end of treatment (Week 24 or 48) | The SVR 24 was defined as hepatitis C virus (HCV) ribonucleic acid (RNA) levels less than (\<) 25 international unit per milliliter (IU/mL) undetectable at the actual 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. |
| Mean Change From Baseline in Log10 Plasma Human Immunodeficiency Virus (HIV) Viral Load | Baseline (Day 1), Week 2, 4, 8, 12, 16, 20, 24, 28, 36, 42, 48, 52, 60 and 72 | — |
| Mean Change From Baseline in CD4+ Cell Count | Baseline (Day 1), Week 2, 4, 8, 12, 16, 20, 24, 28, 36, 42, 48, 52, 60 and 72 | — |
| Change From Baseline in CD4+ Cell Count in Percentage | Baseline (Day 1), Week 2, 4, 8, 12, 16, 20, 24, 28, 36, 42, 48, 52, 60 and 72 | — |
| Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | Week 1 to Week 72 | 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. |
| Percentage of Human Immunodeficiency Virus (HIV) Participants With Virologic Failure | Baseline to Week 72. | 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. |
Countries
Canada, France, Germany, Portugal, Puerto Rico, Spain, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| TMC435 150mg 12Wks PR24/48 Participants received TMC435, 150 mg once daily plus peginterferon alfa-2a (PegIFN alfa-2a) and ribavirin (RBV) for 12 Weeks, 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. | 106 |
| Total | 106 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Initiation of new HCV Therapy | 1 |
| Overall Study | Lost to Follow-up | 4 |
| Overall Study | Protocol Violation | 1 |
| Overall Study | Sponsor's Decision | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | TMC435 150mg 12Wks PR24/48 |
|---|---|
| Age, Continuous | 48 years |
| Sex: Female, Male Female | 16 Participants |
| Sex: Female, Male Male | 90 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 103 / 106 |
| serious Total, serious adverse events | 11 / 106 |
Outcome results
Primary
Percentage of Participants With Sustained Virologic Response at Week 12 (SVR 12)
The SVR 12 was defined as hepatitis C virus (HCV) ribonucleic acid (RNA) levels less than (\<) 25 international unit per milliliter (IU/mL) undetectable at the actual 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.
Time frame: 12 weeks after end of treatment (Week 24 or 48)
Population: Intent to treat (ITT) population included all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TMC435 150mg 12Wks PR24/48 | Percentage of Participants With Sustained Virologic Response at Week 12 (SVR 12) | 73.6 percentage of participants |
Secondary
Change From Baseline in CD4+ Cell Count in Percentage
Time frame: Baseline (Day 1), Week 2, 4, 8, 12, 16, 20, 24, 28, 36, 42, 48, 52, 60 and 72
Population: 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 analyzed for this outcome measure at spcific time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TMC435 150mg 12Wks PR24/48 | Change From Baseline in CD4+ Cell Count in Percentage | Change at Week 60 (n=40) | 0.25 percentage of lymphocyte | Standard Deviation 5.296 |
| TMC435 150mg 12Wks PR24/48 | Change From Baseline in CD4+ Cell Count in Percentage | Baseline (n=93) | 31.65 percentage of lymphocyte | Standard Deviation 8.39 |
| TMC435 150mg 12Wks PR24/48 | Change From Baseline in CD4+ Cell Count in Percentage | Change at Week 2 (n=89) | 0.42 percentage of lymphocyte | Standard Deviation 6.49 |
| TMC435 150mg 12Wks PR24/48 | Change From Baseline in CD4+ Cell Count in Percentage | Change at Week 4 (n=91) | 2.50 percentage of lymphocyte | Standard Deviation 5.943 |
| TMC435 150mg 12Wks PR24/48 | Change From Baseline in CD4+ Cell Count in Percentage | Change at Week 8 (n=92) | 3.85 percentage of lymphocyte | Standard Deviation 5.93 |
| TMC435 150mg 12Wks PR24/48 | Change From Baseline in CD4+ Cell Count in Percentage | Change at Week 12 (n=91) | 3.93 percentage of lymphocyte | Standard Deviation 6.264 |
| TMC435 150mg 12Wks PR24/48 | Change From Baseline in CD4+ Cell Count in Percentage | Change at Week 16 (n=88) | 5.47 percentage of lymphocyte | Standard Deviation 6.301 |
| TMC435 150mg 12Wks PR24/48 | Change From Baseline in CD4+ Cell Count in Percentage | Change at Week 20 (n=84) | 5.27 percentage of lymphocyte | Standard Deviation 6.961 |
| TMC435 150mg 12Wks PR24/48 | Change From Baseline in CD4+ Cell Count in Percentage | Change at Week 24 (n=89) | 5.50 percentage of lymphocyte | Standard Deviation 7.029 |
| TMC435 150mg 12Wks PR24/48 | Change From Baseline in CD4+ Cell Count in Percentage | Change at Week 28 (n=82) | 3.79 percentage of lymphocyte | Standard Deviation 6.759 |
| TMC435 150mg 12Wks PR24/48 | Change From Baseline in CD4+ Cell Count in Percentage | Change at Week 36 (n=83) | 2.75 percentage of lymphocyte | Standard Deviation 6.492 |
| TMC435 150mg 12Wks PR24/48 | Change From Baseline in CD4+ Cell Count in Percentage | Change at Week 42 (n=33) | 6.41 percentage of lymphocyte | Standard Deviation 6.213 |
| TMC435 150mg 12Wks PR24/48 | Change From Baseline in CD4+ Cell Count in Percentage | Change at Week 48 (n=77) | 2.09 percentage of lymphocyte | Standard Deviation 7.356 |
| TMC435 150mg 12Wks PR24/48 | Change From Baseline in CD4+ Cell Count in Percentage | Change at Week 52 (n=35) | 3.26 percentage of lymphocyte | Standard Deviation 6.838 |
| TMC435 150mg 12Wks PR24/48 | Change From Baseline in CD4+ Cell Count in Percentage | Change at Week 72 (n=38) | 0.70 percentage of lymphocyte | Standard Deviation 4.406 |
| TMC435 150mg 12Wks PR24/48 | Change From Baseline in CD4+ Cell Count in Percentage | Change at End of study (n=93) | 0.13 percentage of lymphocyte | Standard Deviation 6.169 |
Secondary
Mean Change From Baseline in CD4+ Cell Count
Time frame: Baseline (Day 1), Week 2, 4, 8, 12, 16, 20, 24, 28, 36, 42, 48, 52, 60 and 72
Population: 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 analyzed for this outcome measure at spcific time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TMC435 150mg 12Wks PR24/48 | Mean Change From Baseline in CD4+ Cell Count | Baseline (n=93) | 640.3 cell counts per microliter | Standard Deviation 243.11 |
| TMC435 150mg 12Wks PR24/48 | Mean Change From Baseline in CD4+ Cell Count | Change at Week 2 (n=89) | -95.0 cell counts per microliter | Standard Deviation 190.34 |
| TMC435 150mg 12Wks PR24/48 | Mean Change From Baseline in CD4+ Cell Count | Change at Week 4 (n=91) | -171.5 cell counts per microliter | Standard Deviation 170.67 |
| TMC435 150mg 12Wks PR24/48 | Mean Change From Baseline in CD4+ Cell Count | Change at Week 8 (n=92) | -244.2 cell counts per microliter | Standard Deviation 185.04 |
| TMC435 150mg 12Wks PR24/48 | Mean Change From Baseline in CD4+ Cell Count | Change at Week 12 (n=91) | -271.7 cell counts per microliter | Standard Deviation 194.49 |
| TMC435 150mg 12Wks PR24/48 | Mean Change From Baseline in CD4+ Cell Count | Change at Week 16 (n=88) | -275.5 cell counts per microliter | Standard Deviation 183.96 |
| TMC435 150mg 12Wks PR24/48 | Mean Change From Baseline in CD4+ Cell Count | Change at Week 20 (n=84) | -283.5 cell counts per microliter | Standard Deviation 175.27 |
| TMC435 150mg 12Wks PR24/48 | Mean Change From Baseline in CD4+ Cell Count | Change at Week 24 (n=89) | -288.8 cell counts per microliter | Standard Deviation 202.31 |
| TMC435 150mg 12Wks PR24/48 | Mean Change From Baseline in CD4+ Cell Count | Change at Week 28 (n=82) | -252.3 cell counts per microliter | Standard Deviation 203.45 |
| TMC435 150mg 12Wks PR24/48 | Mean Change From Baseline in CD4+ Cell Count | Change at Week 36 (n=83) | -198.7 cell counts per microliter | Standard Deviation 225.62 |
| TMC435 150mg 12Wks PR24/48 | Mean Change From Baseline in CD4+ Cell Count | Change at Week 42 (n=33) | -336.8 cell counts per microliter | Standard Deviation 240.64 |
| TMC435 150mg 12Wks PR24/48 | Mean Change From Baseline in CD4+ Cell Count | Change at Week 48 (n=77) | -166.6 cell counts per microliter | Standard Deviation 248.25 |
| TMC435 150mg 12Wks PR24/48 | Mean Change From Baseline in CD4+ Cell Count | Change at Week 52 (n=35) | -202.7 cell counts per microliter | Standard Deviation 222.89 |
| TMC435 150mg 12Wks PR24/48 | Mean Change From Baseline in CD4+ Cell Count | Change at Week 60 (n=40) | -90.6 cell counts per microliter | Standard Deviation 189.74 |
| TMC435 150mg 12Wks PR24/48 | Mean Change From Baseline in CD4+ Cell Count | Change at Week 72 (n=38) | -62.9 cell counts per microliter | Standard Deviation 175.61 |
| TMC435 150mg 12Wks PR24/48 | Mean Change From Baseline in CD4+ Cell Count | Change at End of Study (n=93) | -51.1 cell counts per microliter | Standard Deviation 178.2 |
Secondary
Mean Change From Baseline in Log10 Plasma Human Immunodeficiency Virus (HIV) Viral Load
Time frame: Baseline (Day 1), Week 2, 4, 8, 12, 16, 20, 24, 28, 36, 42, 48, 52, 60 and 72
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TMC435 150mg 12Wks PR24/48 | Mean Change From Baseline in Log10 Plasma Human Immunodeficiency Virus (HIV) Viral Load | Baseline (n=93) | 1.3726 copies per milliliter | Standard Deviation 0.25796 |
| TMC435 150mg 12Wks PR24/48 | Mean Change From Baseline in Log10 Plasma Human Immunodeficiency Virus (HIV) Viral Load | Change at Week 2 (n=91) | -0.0724 copies per milliliter | Standard Deviation 0.23857 |
| TMC435 150mg 12Wks PR24/48 | Mean Change From Baseline in Log10 Plasma Human Immunodeficiency Virus (HIV) Viral Load | Change at Week 4 (n=93) | -0.0704 copies per milliliter | Standard Deviation 0.25817 |
| TMC435 150mg 12Wks PR24/48 | Mean Change From Baseline in Log10 Plasma Human Immunodeficiency Virus (HIV) Viral Load | Change at Week 8 (n=92) | -0.0442 copies per milliliter | Standard Deviation 0.40974 |
| TMC435 150mg 12Wks PR24/48 | Mean Change From Baseline in Log10 Plasma Human Immunodeficiency Virus (HIV) Viral Load | Change at Week 12 (n=90) | -0.0655 copies per milliliter | Standard Deviation 0.3051 |
| TMC435 150mg 12Wks PR24/48 | Mean Change From Baseline in Log10 Plasma Human Immunodeficiency Virus (HIV) Viral Load | Change at Week 16 (n=88) | -0.0829 copies per milliliter | Standard Deviation 0.23986 |
| TMC435 150mg 12Wks PR24/48 | Mean Change From Baseline in Log10 Plasma Human Immunodeficiency Virus (HIV) Viral Load | Change at Week 20 (n=86) | -0.0847 copies per milliliter | Standard Deviation 0.25111 |
| TMC435 150mg 12Wks PR24/48 | Mean Change From Baseline in Log10 Plasma Human Immunodeficiency Virus (HIV) Viral Load | Change at Week 24 (n=88) | -0.0689 copies per milliliter | Standard Deviation 0.24785 |
| TMC435 150mg 12Wks PR24/48 | Mean Change From Baseline in Log10 Plasma Human Immunodeficiency Virus (HIV) Viral Load | Change at Week 28 (n=82) | -0.0564 copies per milliliter | Standard Deviation 0.26319 |
| TMC435 150mg 12Wks PR24/48 | Mean Change From Baseline in Log10 Plasma Human Immunodeficiency Virus (HIV) Viral Load | Change at Week 36 (n=85) | 0.0004 copies per milliliter | Standard Deviation 0.24395 |
| TMC435 150mg 12Wks PR24/48 | Mean Change From Baseline in Log10 Plasma Human Immunodeficiency Virus (HIV) Viral Load | Change at Week 42 (n=35) | -0.0623 copies per milliliter | Standard Deviation 0.29365 |
| TMC435 150mg 12Wks PR24/48 | Mean Change From Baseline in Log10 Plasma Human Immunodeficiency Virus (HIV) Viral Load | Change at Week 48 (n=79) | -0.0041 copies per milliliter | Standard Deviation 0.36177 |
| TMC435 150mg 12Wks PR24/48 | Mean Change From Baseline in Log10 Plasma Human Immunodeficiency Virus (HIV) Viral Load | Change at Week 52 (n=36) | 0.0011 copies per milliliter | Standard Deviation 0.20767 |
| TMC435 150mg 12Wks PR24/48 | Mean Change From Baseline in Log10 Plasma Human Immunodeficiency Virus (HIV) Viral Load | Change at Week 60 (n=40) | -0.0184 copies per milliliter | Standard Deviation 0.2094 |
| TMC435 150mg 12Wks PR24/48 | Mean Change From Baseline in Log10 Plasma Human Immunodeficiency Virus (HIV) Viral Load | Change at Week 72 (n=38) | -0.0265 copies per milliliter | Standard Deviation 0.18323 |
| TMC435 150mg 12Wks PR24/48 | Mean Change From Baseline in Log10 Plasma Human Immunodeficiency Virus (HIV) Viral Load | Change at End of study (n=93) | 0.0099 copies per milliliter | Standard Deviation 0.33435 |
Secondary
Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
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.
Time frame: Week 1 to Week 72
Population: Safety population included all participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TMC435 150mg 12Wks PR24/48 | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TEAEs | 102 participants |
| TMC435 150mg 12Wks PR24/48 | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TESAEs | 6 participants |
Secondary
Percentage of Human Immunodeficiency Virus (HIV) Participants With Virologic Failure
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.
Time frame: Baseline to Week 72.
Population: Participants who received potent anti-HIV treatment with a combination of more than 3 anti-antiretroviral therapies to reduce HIV RNA viral load to undetectable levels were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TMC435 150mg 12Wks PR24/48 | Percentage of Human Immunodeficiency Virus (HIV) Participants With Virologic Failure | Greater than or equal to 50 copies/mL | 5.4 percentage of participants |
| TMC435 150mg 12Wks PR24/48 | Percentage of Human Immunodeficiency Virus (HIV) Participants With Virologic Failure | Greater than or equal to 200 copies/mL | 2.2 percentage of participants |
Secondary
Percentage of Participants With Hepatitis C Virus Ribonucleic Acid (HCV-RNA) Less Than (<) 25 International Units (IU/mL) Undetectable or Detectable/Undetectable
Percentage of participants with HCV RNA less than (\<) 25 IU/mL undetectable (undet.) or detectable (det.)/undetectable at specific time points were observed.
Time frame: Week 4, 12, 24, 36, and 48
Population: ITT population included all participants who had at least 1 dose of study drug. Here, N (number of participants analyzed) is the number of participants analyzed for this outcome measure, n is the number of participants analyzed for this outcome measure at specific time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TMC435 150mg 12Wks PR24/48 | Percentage of Participants With Hepatitis C Virus Ribonucleic Acid (HCV-RNA) Less Than (<) 25 International Units (IU/mL) Undetectable or Detectable/Undetectable | Week 4: < 25 IU/mL HCV-RNA undet. (n=105) | 65.7 percentage of participants |
| TMC435 150mg 12Wks PR24/48 | Percentage of Participants With Hepatitis C Virus Ribonucleic Acid (HCV-RNA) Less Than (<) 25 International Units (IU/mL) Undetectable or Detectable/Undetectable | Week 4:< 25 IU/mL HCV-RNA det./undet. (n=105) | 88.6 percentage of participants |
| TMC435 150mg 12Wks PR24/48 | Percentage of Participants With Hepatitis C Virus Ribonucleic Acid (HCV-RNA) Less Than (<) 25 International Units (IU/mL) Undetectable or Detectable/Undetectable | Week 12:< 25 IU/mL HCV-RNA undet. (n=97) | 94.8 percentage of participants |
| TMC435 150mg 12Wks PR24/48 | Percentage of Participants With Hepatitis C Virus Ribonucleic Acid (HCV-RNA) Less Than (<) 25 International Units (IU/mL) Undetectable or Detectable/Undetectable | Week 12:< 25 IU/mL HCV-RNA det./undet. (n=97) | 97.9 percentage of participants |
| TMC435 150mg 12Wks PR24/48 | Percentage of Participants With Hepatitis C Virus Ribonucleic Acid (HCV-RNA) Less Than (<) 25 International Units (IU/mL) Undetectable or Detectable/Undetectable | Week 24:< 25 IU/mL HCV-RNA undet. (n=90) | 90.0 percentage of participants |
| TMC435 150mg 12Wks PR24/48 | Percentage of Participants With Hepatitis C Virus Ribonucleic Acid (HCV-RNA) Less Than (<) 25 International Units (IU/mL) Undetectable or Detectable/Undetectable | Week 24:< 25 IU/mL HCV-RNA det./undet. (n=90) | 93.3 percentage of participants |
| TMC435 150mg 12Wks PR24/48 | Percentage of Participants With Hepatitis C Virus Ribonucleic Acid (HCV-RNA) Less Than (<) 25 International Units (IU/mL) Undetectable or Detectable/Undetectable | Week 48:< 25 IU/mL HCV-RNA undet. (n=20) | 100 percentage of participants |
| TMC435 150mg 12Wks PR24/48 | Percentage of Participants With Hepatitis C Virus Ribonucleic Acid (HCV-RNA) Less Than (<) 25 International Units (IU/mL) Undetectable or Detectable/Undetectable | Week 48:< 25 IU/mL HCV-RNA det./undet. (n=20) | 100 percentage of participants |
Secondary
Percentage of Participants With Normalized Alanine Aminotransferase Levels
Participants with normalized alanine aminotransferase levels observed whose alanine aminotransferase levels were out of range at Baseline.
Time frame: Baseline up to Week 72
Population: The ITT population included all participants who received at least 1 dose of study drug. Here N signifies participants evaluable for this measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TMC435 150mg 12Wks PR24/48 | Percentage of Participants With Normalized Alanine Aminotransferase Levels | 81.5 percentage of participants |
Secondary
Percentage of Participants With On-treatment Failure
Participants were considered as an on-treatment failure if, at actual end of treatment (EOT), there was confirmed detectable HCV RNA levels.
Time frame: Week 1 to 48
Population: The ITT population included all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TMC435 150mg 12Wks PR24/48 | Percentage of Participants With On-treatment Failure | 17 percentage of participants |
Secondary
Percentage of Participants With Sustained Virologic Response at Week 24 (SVR 24)
The SVR 24 was defined as hepatitis C virus (HCV) ribonucleic acid (RNA) levels less than (\<) 25 international unit per milliliter (IU/mL) undetectable at the actual 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.
Time frame: 24 weeks after end of treatment (Week 24 or 48)
Population: The ITT population included all perticipants who had at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TMC435 150mg 12Wks PR24/48 | Percentage of Participants With Sustained Virologic Response at Week 24 (SVR 24) | 72.6 percentage of participants |
Secondary
Percentage of Participants With Viral Breakthrough
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.
Time frame: Week 1 to 48
Population: The ITT population included all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TMC435 150mg 12Wks PR24/48 | Percentage of Participants With Viral Breakthrough | 11.4 percentage of participants |
Secondary
Percentage of Participants With Viral Relapse
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.
Time frame: Week 1 to 72
Population: The ITT population included all participants who received at least 1 dose of study drug. Here, N (number of participants analyzed) is the number of participants analyzed for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TMC435 150mg 12Wks PR24/48 | Percentage of Participants With Viral Relapse | 10.3 percentage of participants |