There are 4 clinical trials
1. Achieve sustained virologic response (SVR) in patients infected with HCV genotype 1, cirrhosis, and early clinical decompensation using 12 weeks of Olysio/Sovaldi/Ribavirin (or known as: Simeprevir(SMV)/Sofosbuvir(SOF)/Ribavirin (RBV). 2. Hepatic improvement during and after Simeprevir(SMV)/Sofosbuvir(SOF)/Ribavirin(RBV) treatment using a new test of liver function, HepQuant-SHUNT.
Inclusion Criteria: 1. HCV genotype 1 infection (all subtypes and Q80K a type of mutation are allowed), and have been approved by a third party payer for the FDA-approved combination of sofosbuvir (SOF) plus ribavirin. --- Q80K ---
The purpose of this study is to investigate durability of SVR in chronic HCV patients who achieved SVR in the previous study with TMC435-containing regimen and time for resistance associated mutations to return to baseline in chronic HCV patients who did not achieve SVR in the previous study with TMC435-containing regimen.
AEM and NEM represents any emerging mutation and no emerging mutation at time of failure of the previous study.. Percentage of Participants With Change in Sequence of HCV NS3/4A Region Over Time in Participants With Confirmed Detectable HCV RNA (With Q80K at Baseline) at the Last Visit of the Previous Study. --- Q80K ---
AEM and NEM represents any emerging mutation and no emerging mutation at time of failure of the previous study.. Percentage of Participants With Change in Sequence of HCV NS3/4A Region Over Time in Participants With Confirmed Detectable HCV RNA (Without Q80K at Baseline) at the Last Visit of the Previous Study. --- Q80K ---
Description: The SVR rate is the proportion (%) of participants with HCV RNA less than (<) 25 International Units/milliliter (IU/mL).
Measure: Percentage of Participants Maintaining SVR at the Last Available Visit Time: Last Available Visit (Month 36 for subjects completing the study)Description: Sequencing was performed to assess changes in the sequence of the HCV NS3/4A protein region over time in participants with no SVR at LPVPS (ie confirmed detectable HCV RNA at the last visit of the previous study). EOS defined as last available sequencing sample. AEM and NEM represents any emerging mutation and no emerging mutation at time of failure of the previous study.
Measure: Overall Percentage of Participants With Change in Sequence of HCV NS3/4A Region Over Time in Participants With Confirmed Detectable HCV RNA at the Last Visit of the Previous Study Time: Baseline and Month 36Description: Sequencing was performed to assess changes in the sequence of the HCV NS3/4A protein region over time in participants with no SVR at LPVPS (ie confirmed detectable HCV RNA at the last visit of the previous study). EOS defined as last available sequencing sample. AEM and NEM represents any emerging mutation and no emerging mutation at time of failure of the previous study.
Measure: Percentage of Participants With Change in Sequence of HCV NS3/4A Region Over Time in Participants With Confirmed Detectable HCV RNA (With Q80K at Baseline) at the Last Visit of the Previous Study Time: Baseline and Month 36Description: Sequencing was performed to assess changes in the sequence of the HCV NS3/4A protein region over time in participants with no SVR at LPVPS (ie confirmed detectable HCV RNA at the last visit of the previous study). EOS defined as last available sequencing sample. AEM and NEM represents any emerging mutation and no emerging mutation at time of failure of the previous study.
Measure: Percentage of Participants With Change in Sequence of HCV NS3/4A Region Over Time in Participants With Confirmed Detectable HCV RNA (Without Q80K at Baseline) at the Last Visit of the Previous Study Time: Baseline and Month 36Description: Relapse at any time after the LPVPS until the last individual visit of this study. All participants maintained SVR until the last available visit. No late viral relapse was therefore observed.
Measure: Percentage of Participants With Late Viral Relapse Time: End of study (at month 36)The purpose of this study is to evaluate the efficacy of 6 or 8 weeks of treatment regimen containing simeprevir (SMV), daclatasvir (DCV) and sofosbuvir (SOF) in treatment-naive (not having received treatment with any approved or investigational drug) participants with chronic hepatitis (inflammation of the liver) C virus (HCV) genotype 1 infection with early stages of liver fibrosis or with cirrhosis.
Sequencing of the HCV nonstructural protein 3/4A (NS3/4A), nonstructural protein 5A (NS5A) and nonstructural protein 5B (NS5B) genes was done to identify preexisting sequence polymorphisms and characterize emerging HCV viral variants in participants not achieving SVR.. Percentage of Participants With or Without an NS3 Q80K Polymorphism at Baseline Achieving SVR. --- Q80K ---
The Q80K polymorphism, associated with low level SMV in vitro resistance. --- Q80K ---
Percentage of participants who achieved SVR with or without an NS3 Q80K polymorphism at baseline were reported.. Inclusion Criteria: - HCV genotype 1 infection and HCV RNA plasma level greater than (>) 10,000 international units per milliliter (IU/mL), both determined at Screening - Participants of Arm A should have evidence of early stages of liver fibrosis, defined by a FibroSURE score less than or equal to (<=) 0.48 and aspartate aminotransferase to platelet ratio index (APRI) score <=1 - Participants of Arm B should have evidence of cirrhosis, defined by a FibroSURE score >0.75 and APRI score >2, OR a previous (historical) biopsy documenting a METAVIR score F4. --- Q80K ---
Description: Participants were considered to have achieved SVR12 if the hepatitis C virus ribonucleic acid (HCV RNA) was less than (<) lower limit of quantification (LLOQ; 15 international unit per milliliter [IU/mL]) detectable or undetectable at 12 weeks after the end of study drug treatment.
Measure: Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After End of Study Drug Treatment (SVR12) Time: 12 weeks after end of study drug treatment (week 18 for Arm A and week 20 for Arm B)Description: On-treatment virologic response was determined by hepatitis C virus (HCV) ribonucleic acid (RNA) results satisfying a specified threshold.
The following thresholds were considered at any time point:
Description: Participants were considered to have achieved SVR4 and SVR24 if the HCV RNA was
Description: Participants who did not achieve SVR12 and with confirmed detectable HCV RNA at the actual end of treatment. Includes participants with: 1) viral breakthrough, defined as a confirmed increase of greater than (>)1 log10 in HCV RNA from nadir, or confirmed HCV RNA 2) confirmed detectable HCV RNA at the actual end of treatment (example, completed treatment, discontinued due to adverse events, withdrawal of consent) of >100 IU/mL in participants whose HCV RNA had previously been
Description: Viral Relapse: Participants who did not achieve SVR12, with undetectable HCV RNA at the actual end of study drug treatment and confirmed HCV RNA greater than or equal to (>=) LLOQ during followup.
Measure: Number of Participants With Viral Relapse Time: From Week 6 to Week 18 (for Arm A) and From Week 8 to Week 20 (for Arm B)Description: Late Viral Relapse: Participant who achieved SVR12 and the post treatment HCV RNA measurement fulfilled 1 the following conditions: a) at least 2 consecutive measurements not lesser than (<)15 IU/mL undetectable, of which at least the second measurement was >=15 IU/mL quantifiable or b) the last available measurement was >=15 IU/mL quantifiable.
Measure: Number of Participants With Late Viral Relapse Time: From Week 18 to Week 30 (for Arm A), From Week 20 to Week 32 (for Arm B)Description: Sequencing of the HCV nonstructural protein 3/4A (NS3/4A), nonstructural protein 5A (NS5A) and nonstructural protein 5B (NS5B) genes was done to identify preexisting sequence polymorphisms and characterize emerging HCV viral variants in participants not achieving SVR.
Measure: Number of Participants With HCV Nonstructural Protein 3/4A (NS3/4A), NS5A and NS5B Sequence in Participants Not Achieving SVR Time: Up to Week 30 for Arm A and up to Week 32 for Arm BDescription: The Q80K polymorphism, associated with low level SMV in vitro resistance. Percentage of participants who achieved SVR with or without an NS3 Q80K polymorphism at baseline were reported.
Measure: Percentage of Participants With or Without an NS3 Q80K Polymorphism at Baseline Achieving SVR Time: up to Week 30 for Arm A and Week 32 for Arm BThe purpose of the study is to evaluate the efficacy and safety of a treatment regimen of 12 weeks or 8 weeks of simeprevir in combination with sofosbuvir in chronic hepatitis C virus (HCV) genotype 1 infected men and women without cirrhosis who are HCV treatment-naïve or treatment-experienced.
Lower scores indicate worsening.. Inclusion Criteria: - Hepatitis C virus (HCV) genotype 1a or 1b infection confirmed before randomization - Documentation of the presence or absence of a NS3 Q80K polymorphism in HCV genotype 1a infected participants before randomization - Documentation of the IL28B genotype before randomization - HCV ribonucleic acid level greater than 10,000 IU/mL at screening - Treatment-experienced participants must have at least 1 documented previous course of interferon-based regimen with or without ribavirin - Absence of cirrhosis in participants Exclusion Criteria: - Evidence of clinical hepatic decompensation (history or current evidence of ascites, bleeding varices or hepatic encephalopathy) - Infection/co-infection with HCV non-genotype 1a or 1b - Co-infection with human immunodeficiency virus (HIV) type 1 or type 2 (HIV-1 or HIV-2) (positive HIV-1 or HIV-2 antibodies test at screening) - Co-infection with hepatitis-B virus (hepatitis-B-surface-antigen positive) - Previously been treated with any direct acting anti-HCV agent (approved or investigational) for chronic HCV infection Inclusion Criteria: - Hepatitis C virus (HCV) genotype 1a or 1b infection confirmed before randomization - Documentation of the presence or absence of a NS3 Q80K polymorphism in HCV genotype 1a infected participants before randomization - Documentation of the IL28B genotype before randomization - HCV ribonucleic acid level greater than 10,000 IU/mL at screening - Treatment-experienced participants must have at least 1 documented previous course of interferon-based regimen with or without ribavirin - Absence of cirrhosis in participants Exclusion Criteria: - Evidence of clinical hepatic decompensation (history or current evidence of ascites, bleeding varices or hepatic encephalopathy) - Infection/co-infection with HCV non-genotype 1a or 1b - Co-infection with human immunodeficiency virus (HIV) type 1 or type 2 (HIV-1 or HIV-2) (positive HIV-1 or HIV-2 antibodies test at screening) - Co-infection with hepatitis-B virus (hepatitis-B-surface-antigen positive) - Previously been treated with any direct acting anti-HCV agent (approved or investigational) for chronic HCV infection Hepatitis C Virus Infection Infection Communicable Diseases Hepatitis Hepatitis A Hepatitis C Fibrosis Liver Cirrhosis Virus Diseases This is a randomized (the study medication is assigned by chance), open-label (all people know the identity of the intervention), multicenter study. --- Q80K ---
Lower scores indicate worsening.. Inclusion Criteria: - Hepatitis C virus (HCV) genotype 1a or 1b infection confirmed before randomization - Documentation of the presence or absence of a NS3 Q80K polymorphism in HCV genotype 1a infected participants before randomization - Documentation of the IL28B genotype before randomization - HCV ribonucleic acid level greater than 10,000 IU/mL at screening - Treatment-experienced participants must have at least 1 documented previous course of interferon-based regimen with or without ribavirin - Absence of cirrhosis in participants Exclusion Criteria: - Evidence of clinical hepatic decompensation (history or current evidence of ascites, bleeding varices or hepatic encephalopathy) - Infection/co-infection with HCV non-genotype 1a or 1b - Co-infection with human immunodeficiency virus (HIV) type 1 or type 2 (HIV-1 or HIV-2) (positive HIV-1 or HIV-2 antibodies test at screening) - Co-infection with hepatitis-B virus (hepatitis-B-surface-antigen positive) - Previously been treated with any direct acting anti-HCV agent (approved or investigational) for chronic HCV infection Inclusion Criteria: - Hepatitis C virus (HCV) genotype 1a or 1b infection confirmed before randomization - Documentation of the presence or absence of a NS3 Q80K polymorphism in HCV genotype 1a infected participants before randomization - Documentation of the IL28B genotype before randomization - HCV ribonucleic acid level greater than 10,000 IU/mL at screening - Treatment-experienced participants must have at least 1 documented previous course of interferon-based regimen with or without ribavirin - Absence of cirrhosis in participants Exclusion Criteria: - Evidence of clinical hepatic decompensation (history or current evidence of ascites, bleeding varices or hepatic encephalopathy) - Infection/co-infection with HCV non-genotype 1a or 1b - Co-infection with human immunodeficiency virus (HIV) type 1 or type 2 (HIV-1 or HIV-2) (positive HIV-1 or HIV-2 antibodies test at screening) - Co-infection with hepatitis-B virus (hepatitis-B-surface-antigen positive) - Previously been treated with any direct acting anti-HCV agent (approved or investigational) for chronic HCV infection Hepatitis C Virus Infection Infection Communicable Diseases Hepatitis Hepatitis A Hepatitis C Fibrosis Liver Cirrhosis Virus Diseases This is a randomized (the study medication is assigned by chance), open-label (all people know the identity of the intervention), multicenter study. --- Q80K --- --- Q80K ---
Description: Participants considered to have achieved SVR12, if the hepatitis C virus ribonucleic acid (HCV RNA) is less than (<) lower limit of quantification (LLOQ; 25 international unit per milliliter [IU/mL]) detectable or undetectable at 12 weeks after the actual end of study drug treatment.
Measure: Percentage of Participants Achieving a Sustained Virologic Response 12 Weeks After the Actual End of Treatment (SVR12) Time: 12 weeks after the end of treatment (EOT) (Week 20 or Week 24)Description: Participants considered to have achieved SVR4, if the hepatitis C virus ribonucleic acid (HCV RNA) is less than (<) lower limit of quantification (LLOQ; 25 international unit per milliliter [IU/mL]) detectable or undetectable at 4 weeks after the actual end of study drug treatment.
Measure: Percentage of Participants Achieving a Sustained Virologic Response 4 Weeks After the Actual End of Treatment (SVR4) Time: 4 weeks after the end of treatment (EOT) (Week 12 or Week 16)Description: Participants considered to have achieved SVR24, if the hepatitis C virus ribonucleic acid (HCV RNA) is less than (<) lower limit of quantification (LLOQ; 25 international unit per milliliter [IU/mL]) detectable or undetectable at 24 weeks after the Actual end of study drug treatment.
Measure: Percentage of Participants Achieving a Sustained Virologic Response 24 Weeks After the Actual End of Treatment (SVR24) Time: 24 weeks after the end of treatment (EOT) (Week 32 or Week 36)Description: Ontreatment virologic response was determined by HCV RNA results satisfying a specified threshold.
Description: Percentage of participants with greater than 1 log10 IU/mL increase in plasma Hepatitis C virus ribonucleic acid level from the lowest level reached (ie, lowest value measured in between baseline and current value), or a confirmed plasma HCV RNA level of greater than 100 IU/mL in participants whose plasma HCV RNA had previously been less than 25 IU/mL.
Measure: Percentage of Participants With Viral Breakthrough Time: Up to Week 24Description: Percentage of participants who did not achieve sustained virologic response 12, have less than 25 IU/mL undetectable plasma HCV RNA at end of treatment, and greater than or equal to 25 IU/mL plasma HCV RNA during the follow-up phase.
Measure: Percentage of Participants With Viral Relapse Time: Up to Week 24Description: HCVSIQv4 OBSS was a self-administered questionnaire that contained 33 items: 29 questions developed to assess severity or frequency of symptoms associated with HCV or its treatment, 3 questions regarding the impact of symptoms on work/school attendance, and 1 question regarding the impact of symptoms on daily activities. A symptom severity score (the mean of responses to the 29 symptom items); each symptom score was transformed to have a range from 0 to 100 (most severe). Higher HCV SIQv4 scores indicates worse symptom severity, more time missed from work/school, and more impairment in daily activities, respectively.
Measure: Change From Baseline in Hepatitis C Symptom and Impact Questionnaire 4 (HCV-SIQv4) Overall Body System Score (OBSS) Time: Baseline (Day 1), Week 4, Week 8, Week 12, Follow-up Week 4, Follow-up Week 12 and Follow-up Week 24Description: The FSS was a self-administered questionnaire with 9 items developed to assess disabling fatigue that has been used extensively in studies of chronic HCV infection. Item responses were measured on a 7point Likert scale ranging from strongly disagree (1 point) to strongly agree (7 points). The 9 items were averaged to produce a total score; a lower total score indicates less severe fatigue. FSS scores have a range from 1 to 7 where higher scores indicate more severe fatigue.
Measure: Change From Baseline in Fatigue Severity Scale (FSS) Score up to Follow-up Week 24 Time: Baseline (Day 1), Week 4, Week 8, Week 12, Follow-up Week 4, Follow-up Week 12 and Follow-up Week 24Description: The CES-D scale assesses how often during the past week participants experienced 20 symptoms commonly associated with major depression. CES-D scores range from 0 (no symptoms) to 60 (all 20 symptoms most or all of the time during the past 5-7 days). The CES-D scores between 16 and 23 points indicate mild to moderate depressive illness while CES-D scores greater than or equal to 23 indicate probable major depressive illness.
Measure: Change From Baseline in Center for Epidemiologic Studies Depression Scale (CES-D) Scores Time: Baseline (Day 1), Week 4, Week 8, Week 12, Follow-up Week 4, Follow-up Week 12 and Follow-up Week 24Description: The EQ-5D questionnaire is a brief, generic health-related quality of life assessment (HRQOL) that can also be used to incorporate participant preferences into health economic evaluations. The EQ-5D questionnaire assesses HRQOL in terms of degree of limitation on 5 health dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) and as overall health using a "thermometer" visual analog scale with response options ranging from 0 (worst imaginable health) to 100 (best imaginable health). Lower scores indicate worsening.
Measure: Change From Baseline in EuroQol 5 Dimension (EQ-5D) Visual Analogue Scale Time: Baseline (Day 1), Week 4, Week 8, Week 12, Follow-up Week 4, Follow-up Week 12 and Follow-up Week 24