The 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.
Name: Simeprevir
Description: 150 participants will receive 1 capsule of 150 mg simeprevir orally once daily for 12 weeks in Arm 1.Type: DrugArm 1 (Simeprevir/Sofosbuvir)
Name: Simeprevir
Description: 150 participants will receive 1 capsule of 150 mg simeprevir orally once daily for 8 weeks in Arm 2Type: DrugArm 2 (Simeprevir/Sofosbuvir)
Name: Sofosbuvir
Description: 150 participants will receive 1 tablet of 400 mg sofosbuvir orally once daily for 12 weeks in Arm 1.Type: DrugArm 1 (Simeprevir/Sofosbuvir)
Name: Sofosbuvir
Description: 150 participants will receive 1 tablet of 400 mg sofosbuvir orally once daily for 8 weeks in Arm 2.Type: DrugArm 2 (Simeprevir/Sofosbuvir)
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 24Allocation: Randomized
Parallel Assignment
There is one SNP
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 ---