Efficacy and Safety Study of Simeprevir in Combination With Sofosbuvir in Participants With Chronic Hepatitis C Virus Infection Without Cirrhosis

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase 3, Multicenter, Randomized, Open-Label Study to Investigate the Efficacy and Safety of a 12- or 8-Week Treatment Regimen of Simeprevir in Combination With Sofosbuvir in Treatment-Naïve and -Experienced Subjects With Chronic Genotype 1 Hepatitis C Virus Infection Without Cirrhosis

Conditions
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Hepatitis C Virus Infection

Intervention / Treatment
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* Drug: Simeprevir
* Drug: Simeprevir
* Drug: Sofosbuvir
* Drug: Sofosbuvir


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1 (Simeprevir/Sofosbuvir)<br>150 participants will receive 1 capsule of 150 mg simeprevir and 1 tablet of 400 mg sofosbuvir orally (by mouth) once daily for 12 weeks. | Drug: Simeprevir<br>* 150 participants will receive 1 capsule of 150 mg simeprevir orally once daily for 12 weeks in Arm 1.<br>Drug: Sofosbuvir<br>* 150 participants will receive 1 tablet of 400 mg sofosbuvir orally once daily for 12 weeks in Arm 1.<br>|
| Experimental: Arm 2 (Simeprevir/Sofosbuvir)<br>150 participants will receive 1 capsule of 150 mg simeprevir and 1 tablet of 400 mg sofosbuvir orally once daily for 8 weeks. | Drug: Simeprevir<br>* 150 participants will receive 1 capsule of 150 mg simeprevir orally once daily for 8 weeks in Arm 2<br>Drug: Sofosbuvir<br>* 150 participants will receive 1 tablet of 400 mg sofosbuvir orally once daily for 8 weeks in Arm 2.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 12 weeks after the end of treatment (EOT) (Week 20 or Week 24) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 4 weeks after the end of treatment (EOT) (Week 12 or Week 16) | 
| 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. | 24 weeks after the end of treatment (EOT) (Week 32 or Week 36) | 
| 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. | Day 14, Day 28, End of treatment (Week 8 or Week 12) | 
| 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. | Up to Week 24 | 
| 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. | Up to Week 24 | 
| 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. | Baseline (Day 1), Week 4, Week 8, Week 12, Follow-up Week 4, Follow-up Week 12 and Follow-up Week 24 | 
| 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. | Baseline (Day 1), Week 4, Week 8, Week 12, Follow-up Week 4, Follow-up Week 12 and Follow-up Week 24 | 
| 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. | Baseline (Day 1), Week 4, Week 8, Week 12, Follow-up Week 4, Follow-up Week 12 and Follow-up Week 24 | 
| 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. | Baseline (Day 1), Week 4, Week 8, Week 12, Follow-up Week 4, Follow-up Week 12 and Follow-up Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatitis C Virus Infection, Simeprevir, Sofosbuvir, HCV, Cirrhosis