Hepatitis C Virus Infection
Conditions
Keywords
Hepatitis C Virus Infection, Simeprevir, Sofosbuvir, HCV, Cirrhosis
Brief summary
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.
Detailed description
This is a randomized (the study medication is assigned by chance), open-label (all people know the identity of the intervention), multicenter study. The study will consist of a screening phase up to 6 weeks, open-label treatment phase of 8 weeks or 12 weeks, and post-treatment follow up phase up to 24 weeks after end of treatment. Approximately 300 participants will be randomly allocated in a 1:1 ratio to receive 150 mg simeprevir in combination with 400 mg sofosbuvir once daily either for 12 weeks (Arm 1) or 8 weeks (Arm 2). Safety evaluations will include assessment of adverse events, clinical laboratory tests, vital signs, and physical examination. The maximum study duration for each participant will be approximately 42 weeks.
Interventions
DRUGSimeprevir
150 participants will receive 1 capsule of 150 mg simeprevir orally once daily for 12 weeks in Arm 1.
DRUGSofosbuvir
150 participants will receive 1 tablet of 400 mg sofosbuvir orally once daily for 12 weeks in Arm 1.
Sponsors
Janssen Infectious Diseases BVBA
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving a Sustained Virologic Response 12 Weeks After the Actual End of Treatment (SVR12) | 12 weeks after the end of treatment (EOT) (Week 20 or Week 24) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving a Sustained Virologic Response 24 Weeks After the Actual End of Treatment (SVR24) | 24 weeks after the end of treatment (EOT) (Week 32 or Week 36) | 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. |
| Percentage of Participants Achieving a On-treatment Virologic Response | Day 14, Day 28, End of treatment (Week 8 or Week 12) | Ontreatment virologic response was determined by HCV RNA results satisfying a specified threshold. \<LLOQ undetectable was considered as threshold at any time point. The LLOQ value is 25 IU/mL. EOT=End of Treatment. |
| Percentage of Participants With Viral Breakthrough | Up to Week 24 | 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. |
| Percentage of Participants With Viral Relapse | Up to Week 24 | 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. |
| Percentage of Participants Achieving a Sustained Virologic Response 4 Weeks After the Actual End of Treatment (SVR4) | 4 weeks after the end of treatment (EOT) (Week 12 or Week 16) | 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. |
| Change From Baseline in Fatigue Severity Scale (FSS) Score up to Follow-up Week 24 | Baseline (Day 1), Week 4, Week 8, Week 12, Follow-up Week 4, Follow-up Week 12 and Follow-up Week 24 | 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. |
| Change From Baseline in Center for Epidemiologic Studies Depression Scale (CES-D) Scores | Baseline (Day 1), Week 4, Week 8, Week 12, Follow-up Week 4, Follow-up Week 12 and Follow-up Week 24 | 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. |
| Change From Baseline in EuroQol 5 Dimension (EQ-5D) Visual Analogue Scale | Baseline (Day 1), Week 4, Week 8, Week 12, Follow-up Week 4, Follow-up Week 12 and Follow-up Week 24 | 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. |
| Change From Baseline in Hepatitis C Symptom and Impact Questionnaire 4 (HCV-SIQv4) Overall Body System Score (OBSS) | Baseline (Day 1), Week 4, Week 8, Week 12, Follow-up Week 4, Follow-up Week 12 and Follow-up Week 24 | 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. |
Countries
Canada, United States
Participant flow
Pre-assignment details
A total of 310 participants were randomly allocated to the 2 treatment arms. All participants received at least 1 dose of study drug and were included in intent to treat (ITT) analysis set.
Participants by arm
| Arm | Count |
|---|---|
| Simeprevir and Sofosbuvir for 8 Weeks Participants received 1 capsule of 150 milligram (mg) simeprevir and 1 tablet of 400 mg sofosbuvir orally (by mouth) once daily for 8 weeks. | 155 |
| Simeprevir and Sofosbuvir for 12 Weeks Participants received 1 capsule of 150 mg simeprevir and 1 tablet of 400 mg sofosbuvir orally (by mouth) once daily for 12 weeks. | 155 |
| Total | 310 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 2 |
| Overall Study | Other | 2 | 1 |
| Overall Study | Withdrawal by Subject | 6 | 1 |
Baseline characteristics
| Characteristic | Simeprevir and Sofosbuvir for 8 Weeks | Simeprevir and Sofosbuvir for 12 Weeks | Total |
|---|---|---|---|
| Age, Continuous | 56 years | 56 years | 56 years |
| Sex: Female, Male Female | 68 Participants | 73 Participants | 141 Participants |
| Sex: Female, Male Male | 87 Participants | 82 Participants | 169 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 68 / 155 | 65 / 155 |
| serious Total, serious adverse events | 3 / 155 | 2 / 155 |
Outcome results
Primary
Percentage of Participants Achieving a Sustained Virologic Response 12 Weeks After the Actual End of Treatment (SVR12)
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.
Time frame: 12 weeks after the end of treatment (EOT) (Week 20 or Week 24)
Population: Intent-to-treat (ITT) population included all the randomized participants who took at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Simeprevir and Sofosbuvir for 8 Weeks | Percentage of Participants Achieving a Sustained Virologic Response 12 Weeks After the Actual End of Treatment (SVR12) | 82.6 Percentage of participants |
| Simeprevir and Sofosbuvir for 12 Weeks | Percentage of Participants Achieving a Sustained Virologic Response 12 Weeks After the Actual End of Treatment (SVR12) | 96.8 Percentage of participants |
Secondary
Change From Baseline in Center for Epidemiologic Studies Depression Scale (CES-D) Scores
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.
Time frame: Baseline (Day 1), Week 4, Week 8, Week 12, Follow-up Week 4, Follow-up Week 12 and Follow-up Week 24
Population: The ITT population included all the randomized participants who took at least 1 dose of study drug. Here, N (Number of Participants Analyzed) signifies those participants who were evaluable for this outcome measure and 'n' specifies those participants who were evaluated for this outcome measure at given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Simeprevir and Sofosbuvir for 8 Weeks | Change From Baseline in Center for Epidemiologic Studies Depression Scale (CES-D) Scores | Change at Week 8 (n=141, 144) | -0.6 units on a scale | Standard Error 0.73 |
| Simeprevir and Sofosbuvir for 8 Weeks | Change From Baseline in Center for Epidemiologic Studies Depression Scale (CES-D) Scores | Change at Follow-up Week 4 (n=141, 148) | -2.6 units on a scale | Standard Error 0.64 |
| Simeprevir and Sofosbuvir for 8 Weeks | Change From Baseline in Center for Epidemiologic Studies Depression Scale (CES-D) Scores | Change at Week 4 (n=139, 140) | -0.6 units on a scale | Standard Error 0.67 |
| Simeprevir and Sofosbuvir for 8 Weeks | Change From Baseline in Center for Epidemiologic Studies Depression Scale (CES-D) Scores | Change at Follow-up Week 12 (n=140, 145) | -1.5 units on a scale | Standard Error 0.62 |
| Simeprevir and Sofosbuvir for 8 Weeks | Change From Baseline in Center for Epidemiologic Studies Depression Scale (CES-D) Scores | Change at Week 12 (n=141, 144) | NA units on a scale | — |
| Simeprevir and Sofosbuvir for 8 Weeks | Change From Baseline in Center for Epidemiologic Studies Depression Scale (CES-D) Scores | Change at Follow-up Week 24 (n=131, 143) | -2.8 units on a scale | Standard Error 0.72 |
| Simeprevir and Sofosbuvir for 8 Weeks | Change From Baseline in Center for Epidemiologic Studies Depression Scale (CES-D) Scores | Baseline (n=144, 149) | 8.8 units on a scale | Standard Error 0.72 |
| Simeprevir and Sofosbuvir for 12 Weeks | Change From Baseline in Center for Epidemiologic Studies Depression Scale (CES-D) Scores | Change at Follow-up Week 24 (n=131, 143) | -1.0 units on a scale | Standard Error 0.7 |
| Simeprevir and Sofosbuvir for 12 Weeks | Change From Baseline in Center for Epidemiologic Studies Depression Scale (CES-D) Scores | Baseline (n=144, 149) | 10.2 units on a scale | Standard Error 0.71 |
| Simeprevir and Sofosbuvir for 12 Weeks | Change From Baseline in Center for Epidemiologic Studies Depression Scale (CES-D) Scores | Change at Week 4 (n=139, 140) | -0.8 units on a scale | Standard Error 0.52 |
| Simeprevir and Sofosbuvir for 12 Weeks | Change From Baseline in Center for Epidemiologic Studies Depression Scale (CES-D) Scores | Change at Week 8 (n=141, 144) | -0.3 units on a scale | Standard Error 0.66 |
| Simeprevir and Sofosbuvir for 12 Weeks | Change From Baseline in Center for Epidemiologic Studies Depression Scale (CES-D) Scores | Change at Week 12 (n=141, 144) | 1.0 units on a scale | Standard Error 0.72 |
| Simeprevir and Sofosbuvir for 12 Weeks | Change From Baseline in Center for Epidemiologic Studies Depression Scale (CES-D) Scores | Change at Follow-up Week 4 (n=141, 148) | -0.6 units on a scale | Standard Error 0.68 |
| Simeprevir and Sofosbuvir for 12 Weeks | Change From Baseline in Center for Epidemiologic Studies Depression Scale (CES-D) Scores | Change at Follow-up Week 12 (n=140, 145) | -0.1 units on a scale | Standard Error 0.72 |
Secondary
Change From Baseline in EuroQol 5 Dimension (EQ-5D) Visual Analogue Scale
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.
Time frame: Baseline (Day 1), Week 4, Week 8, Week 12, Follow-up Week 4, Follow-up Week 12 and Follow-up Week 24
Population: The ITT population included all the randomized participants who took at least 1 dose of study drug. Here, N (Number of Participants Analyzed) signifies those participants who were evaluable for this outcome measure and 'n' specifies those participants who were evaluated for this outcome measure at given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Simeprevir and Sofosbuvir for 8 Weeks | Change From Baseline in EuroQol 5 Dimension (EQ-5D) Visual Analogue Scale | Change at Week 8 (n=142, 144) | 4.0 units on a scale | Standard Error 1.21 |
| Simeprevir and Sofosbuvir for 8 Weeks | Change From Baseline in EuroQol 5 Dimension (EQ-5D) Visual Analogue Scale | Change at Follow-up Week 4 (n=141, 148) | 6.9 units on a scale | Standard Error 1.34 |
| Simeprevir and Sofosbuvir for 8 Weeks | Change From Baseline in EuroQol 5 Dimension (EQ-5D) Visual Analogue Scale | Change at Week 4 (n=142, 141) | 4.6 units on a scale | Standard Error 1.31 |
| Simeprevir and Sofosbuvir for 8 Weeks | Change From Baseline in EuroQol 5 Dimension (EQ-5D) Visual Analogue Scale | Change at Follow-up Week 12 (n=138, 145) | 5.5 units on a scale | Standard Error 1.27 |
| Simeprevir and Sofosbuvir for 8 Weeks | Change From Baseline in EuroQol 5 Dimension (EQ-5D) Visual Analogue Scale | Change at Week 12 (n=0, 140) | NA units on a scale | — |
| Simeprevir and Sofosbuvir for 8 Weeks | Change From Baseline in EuroQol 5 Dimension (EQ-5D) Visual Analogue Scale | Change at Follow-up Week 24 (n=131, 143) | 6.2 units on a scale | Standard Error 1.51 |
| Simeprevir and Sofosbuvir for 8 Weeks | Change From Baseline in EuroQol 5 Dimension (EQ-5D) Visual Analogue Scale | Baseline (N=144, 149) | 79.3 units on a scale | Standard Error 1.53 |
| Simeprevir and Sofosbuvir for 12 Weeks | Change From Baseline in EuroQol 5 Dimension (EQ-5D) Visual Analogue Scale | Change at Follow-up Week 24 (n=131, 143) | 5.3 units on a scale | Standard Error 1.28 |
| Simeprevir and Sofosbuvir for 12 Weeks | Change From Baseline in EuroQol 5 Dimension (EQ-5D) Visual Analogue Scale | Baseline (N=144, 149) | 76.7 units on a scale | Standard Error 1.48 |
| Simeprevir and Sofosbuvir for 12 Weeks | Change From Baseline in EuroQol 5 Dimension (EQ-5D) Visual Analogue Scale | Change at Week 4 (n=142, 141) | 2.4 units on a scale | Standard Error 1.05 |
| Simeprevir and Sofosbuvir for 12 Weeks | Change From Baseline in EuroQol 5 Dimension (EQ-5D) Visual Analogue Scale | Change at Week 8 (n=142, 144) | 2.7 units on a scale | Standard Error 0.93 |
| Simeprevir and Sofosbuvir for 12 Weeks | Change From Baseline in EuroQol 5 Dimension (EQ-5D) Visual Analogue Scale | Change at Week 12 (n=0, 140) | 2.5 units on a scale | Standard Error 1.14 |
| Simeprevir and Sofosbuvir for 12 Weeks | Change From Baseline in EuroQol 5 Dimension (EQ-5D) Visual Analogue Scale | Change at Follow-up Week 4 (n=141, 148) | 4.4 units on a scale | Standard Error 1.12 |
| Simeprevir and Sofosbuvir for 12 Weeks | Change From Baseline in EuroQol 5 Dimension (EQ-5D) Visual Analogue Scale | Change at Follow-up Week 12 (n=138, 145) | 3.9 units on a scale | Standard Error 1.37 |
Secondary
Change From Baseline in Fatigue Severity Scale (FSS) Score up to Follow-up Week 24
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.
Time frame: Baseline (Day 1), Week 4, Week 8, Week 12, Follow-up Week 4, Follow-up Week 12 and Follow-up Week 24
Population: The ITT population included all the randomized participants who took at least 1 dose of study drug. Here, N (Number of Participants Analyzed) signifies those participants who were evaluable for this outcome measure and 'n' specifies those participants who were evaluated for this outcome measure at given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Simeprevir and Sofosbuvir for 8 Weeks | Change From Baseline in Fatigue Severity Scale (FSS) Score up to Follow-up Week 24 | Change at Week 8 (n=142, 144) | -0.1 units on a scale | Standard Error 0.11 |
| Simeprevir and Sofosbuvir for 8 Weeks | Change From Baseline in Fatigue Severity Scale (FSS) Score up to Follow-up Week 24 | Change at Follow-up Week 4 (n=141, 148) | -0.4 units on a scale | Standard Error 0.12 |
| Simeprevir and Sofosbuvir for 8 Weeks | Change From Baseline in Fatigue Severity Scale (FSS) Score up to Follow-up Week 24 | Change at Week 4 (n=142, 142) | -0.1 units on a scale | Standard Error 0.09 |
| Simeprevir and Sofosbuvir for 8 Weeks | Change From Baseline in Fatigue Severity Scale (FSS) Score up to Follow-up Week 24 | Change at Follow-up Week 12 (n=140, 145) | -0.5 units on a scale | Standard Error 0.11 |
| Simeprevir and Sofosbuvir for 8 Weeks | Change From Baseline in Fatigue Severity Scale (FSS) Score up to Follow-up Week 24 | Change at Week 12 (n=0, 140) | NA units on a scale | — |
| Simeprevir and Sofosbuvir for 8 Weeks | Change From Baseline in Fatigue Severity Scale (FSS) Score up to Follow-up Week 24 | Change at Follow-up Week 24 (n=132, 143) | -0.6 units on a scale | Standard Error 0.13 |
| Simeprevir and Sofosbuvir for 8 Weeks | Change From Baseline in Fatigue Severity Scale (FSS) Score up to Follow-up Week 24 | Baseline (n=144, 149) | 2.9 units on a scale | Standard Error 0.13 |
| Simeprevir and Sofosbuvir for 12 Weeks | Change From Baseline in Fatigue Severity Scale (FSS) Score up to Follow-up Week 24 | Change at Follow-up Week 24 (n=132, 143) | -0.5 units on a scale | Standard Error 0.14 |
| Simeprevir and Sofosbuvir for 12 Weeks | Change From Baseline in Fatigue Severity Scale (FSS) Score up to Follow-up Week 24 | Baseline (n=144, 149) | 3.2 units on a scale | Standard Error 0.14 |
| Simeprevir and Sofosbuvir for 12 Weeks | Change From Baseline in Fatigue Severity Scale (FSS) Score up to Follow-up Week 24 | Change at Week 4 (n=142, 142) | -0.1 units on a scale | Standard Error 0.13 |
| Simeprevir and Sofosbuvir for 12 Weeks | Change From Baseline in Fatigue Severity Scale (FSS) Score up to Follow-up Week 24 | Change at Week 8 (n=142, 144) | -0.2 units on a scale | Standard Error 0.14 |
| Simeprevir and Sofosbuvir for 12 Weeks | Change From Baseline in Fatigue Severity Scale (FSS) Score up to Follow-up Week 24 | Change at Week 12 (n=0, 140) | -0.1 units on a scale | Standard Error 0.15 |
| Simeprevir and Sofosbuvir for 12 Weeks | Change From Baseline in Fatigue Severity Scale (FSS) Score up to Follow-up Week 24 | Change at Follow-up Week 4 (n=141, 148) | -0.4 units on a scale | Standard Error 0.13 |
| Simeprevir and Sofosbuvir for 12 Weeks | Change From Baseline in Fatigue Severity Scale (FSS) Score up to Follow-up Week 24 | Change at Follow-up Week 12 (n=140, 145) | -0.4 units on a scale | Standard Error 0.15 |
Secondary
Change From Baseline in Hepatitis C Symptom and Impact Questionnaire 4 (HCV-SIQv4) Overall Body System Score (OBSS)
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.
Time frame: Baseline (Day 1), Week 4, Week 8, Week 12, Follow-up Week 4, Follow-up Week 12 and Follow-up Week 24
Population: The ITT population included all the randomized participants who took at least 1 dose of study drug. Here, N (Number of Participants Analyzed) signifies those participants who were evaluable for this outcome measure and 'n' specifies those participants who were evaluated for this outcome measure at given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Simeprevir and Sofosbuvir for 8 Weeks | Change From Baseline in Hepatitis C Symptom and Impact Questionnaire 4 (HCV-SIQv4) Overall Body System Score (OBSS) | Change at Week 8 (n=144, 146) | -0.2 units on a scale | Standard Error 1.06 |
| Simeprevir and Sofosbuvir for 8 Weeks | Change From Baseline in Hepatitis C Symptom and Impact Questionnaire 4 (HCV-SIQv4) Overall Body System Score (OBSS) | Change at Follow-up Week 4 (n=142, 148) | -3.5 units on a scale | Standard Error 0.88 |
| Simeprevir and Sofosbuvir for 8 Weeks | Change From Baseline in Hepatitis C Symptom and Impact Questionnaire 4 (HCV-SIQv4) Overall Body System Score (OBSS) | Change at Week 4 (n=145, 146) | -0.4 units on a scale | Standard Error 0.83 |
| Simeprevir and Sofosbuvir for 8 Weeks | Change From Baseline in Hepatitis C Symptom and Impact Questionnaire 4 (HCV-SIQv4) Overall Body System Score (OBSS) | Change at Follow-up Week 12 (n=141, 145) | -2.0 units on a scale | Standard Error 0.86 |
| Simeprevir and Sofosbuvir for 8 Weeks | Change From Baseline in Hepatitis C Symptom and Impact Questionnaire 4 (HCV-SIQv4) Overall Body System Score (OBSS) | Change at Week 12 (n=0, 141) | NA units on a scale | — |
| Simeprevir and Sofosbuvir for 8 Weeks | Change From Baseline in Hepatitis C Symptom and Impact Questionnaire 4 (HCV-SIQv4) Overall Body System Score (OBSS) | Change at Follow-up Week 24 (n=133, 143) | -3.6 units on a scale | Standard Error 0.99 |
| Simeprevir and Sofosbuvir for 8 Weeks | Change From Baseline in Hepatitis C Symptom and Impact Questionnaire 4 (HCV-SIQv4) Overall Body System Score (OBSS) | Baseline (n=145, 149) | 10.8 units on a scale | Standard Error 0.94 |
| Simeprevir and Sofosbuvir for 12 Weeks | Change From Baseline in Hepatitis C Symptom and Impact Questionnaire 4 (HCV-SIQv4) Overall Body System Score (OBSS) | Change at Follow-up Week 24 (n=133, 143) | -4.4 units on a scale | Standard Error 0.9 |
| Simeprevir and Sofosbuvir for 12 Weeks | Change From Baseline in Hepatitis C Symptom and Impact Questionnaire 4 (HCV-SIQv4) Overall Body System Score (OBSS) | Baseline (n=145, 149) | 13.3 units on a scale | Standard Error 1.01 |
| Simeprevir and Sofosbuvir for 12 Weeks | Change From Baseline in Hepatitis C Symptom and Impact Questionnaire 4 (HCV-SIQv4) Overall Body System Score (OBSS) | Change at Week 4 (n=145, 146) | -0.9 units on a scale | Standard Error 0.89 |
| Simeprevir and Sofosbuvir for 12 Weeks | Change From Baseline in Hepatitis C Symptom and Impact Questionnaire 4 (HCV-SIQv4) Overall Body System Score (OBSS) | Change at Week 8 (n=144, 146) | -0.4 units on a scale | Standard Error 0.9 |
| Simeprevir and Sofosbuvir for 12 Weeks | Change From Baseline in Hepatitis C Symptom and Impact Questionnaire 4 (HCV-SIQv4) Overall Body System Score (OBSS) | Change at Week 12 (n=0, 141) | 0.1 units on a scale | Standard Error 0.97 |
| Simeprevir and Sofosbuvir for 12 Weeks | Change From Baseline in Hepatitis C Symptom and Impact Questionnaire 4 (HCV-SIQv4) Overall Body System Score (OBSS) | Change at Follow-up Week 4 (n=142, 148) | -3.0 units on a scale | Standard Error 0.91 |
| Simeprevir and Sofosbuvir for 12 Weeks | Change From Baseline in Hepatitis C Symptom and Impact Questionnaire 4 (HCV-SIQv4) Overall Body System Score (OBSS) | Change at Follow-up Week 12 (n=141, 145) | -3.5 units on a scale | Standard Error 0.96 |
Secondary
Percentage of Participants Achieving a On-treatment Virologic Response
Ontreatment virologic response was determined by HCV RNA results satisfying a specified threshold. \<LLOQ undetectable was considered as threshold at any time point. The LLOQ value is 25 IU/mL. EOT=End of Treatment.
Time frame: Day 14, Day 28, End of treatment (Week 8 or Week 12)
Population: The ITT population included all the randomized participants who took at least 1 dose of study drug. Here, 'n' specifies those participants who were evaluated for this outcome measure at given time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Simeprevir and Sofosbuvir for 8 Weeks | Percentage of Participants Achieving a On-treatment Virologic Response | Day 14: < 25 IU/mL undetectable (n=154, 152) | 37.66 Percentage of participants |
| Simeprevir and Sofosbuvir for 8 Weeks | Percentage of Participants Achieving a On-treatment Virologic Response | Day 28: < 25 IU/mL detectable (n=154, 153) | 16.2 Percentage of participants |
| Simeprevir and Sofosbuvir for 8 Weeks | Percentage of Participants Achieving a On-treatment Virologic Response | Day 14: < 25 IU/mL detectable (n=154, 152) | 40.26 Percentage of participants |
| Simeprevir and Sofosbuvir for 8 Weeks | Percentage of Participants Achieving a On-treatment Virologic Response | Day 28: < 25 IU/mL undetectable (n=154, 153) | 82.5 Percentage of participants |
| Simeprevir and Sofosbuvir for 8 Weeks | Percentage of Participants Achieving a On-treatment Virologic Response | Day 28: < 100 IU/mL (n=154, 153) | 100 Percentage of participants |
| Simeprevir and Sofosbuvir for 8 Weeks | Percentage of Participants Achieving a On-treatment Virologic Response | EOT: < 100 IU/mL (n=155, 155) | 100 Percentage of participants |
| Simeprevir and Sofosbuvir for 8 Weeks | Percentage of Participants Achieving a On-treatment Virologic Response | Day 14: < 25 IU/mL (n=154, 152) | 77.92 Percentage of participants |
| Simeprevir and Sofosbuvir for 8 Weeks | Percentage of Participants Achieving a On-treatment Virologic Response | EOT: < 25 IU/mL (n=155, 155) | 100 Percentage of participants |
| Simeprevir and Sofosbuvir for 8 Weeks | Percentage of Participants Achieving a On-treatment Virologic Response | Day 28: < 25 IU/mL (n=154, 153) | 98.7 Percentage of participants |
| Simeprevir and Sofosbuvir for 8 Weeks | Percentage of Participants Achieving a On-treatment Virologic Response | EOT: < 25 IU/mL undetectable (n=155, 155) | 100 Percentage of participants |
| Simeprevir and Sofosbuvir for 8 Weeks | Percentage of Participants Achieving a On-treatment Virologic Response | Day 14: < 100 IU/mL (n=154, 152) | 90.9 Percentage of participants |
| Simeprevir and Sofosbuvir for 12 Weeks | Percentage of Participants Achieving a On-treatment Virologic Response | EOT: < 25 IU/mL undetectable (n=155, 155) | 100 Percentage of participants |
| Simeprevir and Sofosbuvir for 12 Weeks | Percentage of Participants Achieving a On-treatment Virologic Response | Day 14: < 100 IU/mL (n=154, 152) | 93.4 Percentage of participants |
| Simeprevir and Sofosbuvir for 12 Weeks | Percentage of Participants Achieving a On-treatment Virologic Response | Day 14: < 25 IU/mL (n=154, 152) | 79.6 Percentage of participants |
| Simeprevir and Sofosbuvir for 12 Weeks | Percentage of Participants Achieving a On-treatment Virologic Response | Day 14: < 25 IU/mL detectable (n=154, 152) | 45.4 Percentage of participants |
| Simeprevir and Sofosbuvir for 12 Weeks | Percentage of Participants Achieving a On-treatment Virologic Response | Day 14: < 25 IU/mL undetectable (n=154, 152) | 34.2 Percentage of participants |
| Simeprevir and Sofosbuvir for 12 Weeks | Percentage of Participants Achieving a On-treatment Virologic Response | Day 28: < 100 IU/mL (n=154, 153) | 100 Percentage of participants |
| Simeprevir and Sofosbuvir for 12 Weeks | Percentage of Participants Achieving a On-treatment Virologic Response | Day 28: < 25 IU/mL (n=154, 153) | 98.7 Percentage of participants |
| Simeprevir and Sofosbuvir for 12 Weeks | Percentage of Participants Achieving a On-treatment Virologic Response | Day 28: < 25 IU/mL detectable (n=154, 153) | 11.1 Percentage of participants |
| Simeprevir and Sofosbuvir for 12 Weeks | Percentage of Participants Achieving a On-treatment Virologic Response | Day 28: < 25 IU/mL undetectable (n=154, 153) | 87.6 Percentage of participants |
| Simeprevir and Sofosbuvir for 12 Weeks | Percentage of Participants Achieving a On-treatment Virologic Response | EOT: < 100 IU/mL (n=155, 155) | 100 Percentage of participants |
| Simeprevir and Sofosbuvir for 12 Weeks | Percentage of Participants Achieving a On-treatment Virologic Response | EOT: < 25 IU/mL (n=155, 155) | 100 Percentage of participants |
Secondary
Percentage of Participants Achieving a Sustained Virologic Response 24 Weeks After the Actual End of Treatment (SVR24)
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.
Time frame: 24 weeks after the end of treatment (EOT) (Week 32 or Week 36)
Population: Intent-to-treat (ITT) population included all the randomized participants who took at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Simeprevir and Sofosbuvir for 8 Weeks | Percentage of Participants Achieving a Sustained Virologic Response 24 Weeks After the Actual End of Treatment (SVR24) | 82.6 Percentage of participants |
| Simeprevir and Sofosbuvir for 12 Weeks | Percentage of Participants Achieving a Sustained Virologic Response 24 Weeks After the Actual End of Treatment (SVR24) | 96.8 Percentage of participants |
Secondary
Percentage of Participants Achieving a Sustained Virologic Response 4 Weeks After the Actual End of Treatment (SVR4)
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.
Time frame: 4 weeks after the end of treatment (EOT) (Week 12 or Week 16)
Population: Intent-to-treat (ITT) population included all the randomized participants who took at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Simeprevir and Sofosbuvir for 8 Weeks | Percentage of Participants Achieving a Sustained Virologic Response 4 Weeks After the Actual End of Treatment (SVR4) | 83.9 Percentage of Participants |
| Simeprevir and Sofosbuvir for 12 Weeks | Percentage of Participants Achieving a Sustained Virologic Response 4 Weeks After the Actual End of Treatment (SVR4) | 96.8 Percentage of Participants |
Secondary
Percentage of Participants With Viral Breakthrough
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.
Time frame: Up to Week 24
Population: The ITT population included all the randomized participants who took at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Simeprevir and Sofosbuvir for 8 Weeks | Percentage of Participants With Viral Breakthrough | 0 Percentage of participants |
| Simeprevir and Sofosbuvir for 12 Weeks | Percentage of Participants With Viral Breakthrough | 0 Percentage of participants |
Secondary
Percentage of Participants With Viral Relapse
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.
Time frame: Up to Week 24
Population: The ITT population included all the randomized participants who took at least 1 dose of study drug. Here, N (Number of Participants Analyzed) signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Simeprevir and Sofosbuvir for 8 Weeks | Percentage of Participants With Viral Relapse | 17.4 Percentage of participants |
| Simeprevir and Sofosbuvir for 12 Weeks | Percentage of Participants With Viral Relapse | 2.6 Percentage of participants |