A Study to Assess the Efficacy and Safety of the Combination of Simeprevir and Daclatasvir in Chronic Hepatitis C Genotype 1b-Infected Participants

Study Overview
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Brief Summary
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The purpose of this study is to determine the efficacy of a 12- or 24-week treatment regimen of simeprevir in combination with daclatasvir, as measured by sustain virologic response 12 (SVR12), in treatment-naive, chronic hepatitis C virus (HCV) genotype 1b-infected participants who have advanced fibrosis or compensated cirrhosis (METAVIR F3/F4).

Detailed Description
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This is an open-label (all people know which treatment the participants receive) study to investigate the efficacy, safety and tolerability of simeprevir and daclatasvir in chronic Hepatitis (inflammation of the liver) C virus (HCV) genotype 1b infected participants who are treatment-naive. The total study duration for each participant will be approximately 40 weeks or approximately 52 weeks. The study will consist of 4 parts: Screening Phase (approximately 4 weeks) and open-label treatment Phase (12 weeks), optional open label treatment phase extension (12 Weeks) and follow-up Phase (up to Week 40 or Week 52). Participants will receive simeprevir (150 milligram [mg] capsule) and daclatasvir (60 mg tablet) orally once daily for 12 or 24 weeks. Efficacy will be primarily evaluated by percentage of participants with SVR12. Participants' safety will be monitored throughout the study.

Official Title
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A Phase 2, Open-label Study to Investigate the Efficacy and Safety of the Combination of Simeprevir and Daclatasvir in Chronic Hepatitis C Genotype 1b-Infected Subjects

Conditions
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Hepatitis C, Chronic

Intervention / Treatment
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* Drug: Simeprevir
* Drug: Daclatasvir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant must have chronic Hepatitis C virus (HCV) genotype 1b infection confirmed at Screening Participant must have HCV ribonucleic acid (RNA) greater than (>) 10,000 international unit per milliliter (IU/mL) at Screening Participant must have documented fibrosis stage at Screening (or between Screening and Day 1 [baseline]). Liver disease will be staged based on one of the following methods. a) Shear wave elastography (Fibroscan) within less than or equal to (<=) 6 months before Screening or between Screening and Day 1 (baseline). METAVIR F3 > 9.6 Kilopascals (kPa) and the cut-off for cirrhosis is greater than or equal to (>=) 14.6 kPa. b) A biopsy documenting METAVIR F3-F4. Biopsy performed within the 24 months before Screening will be accepted for participants with METAVIR score F3. For cirrhotic participants (METAVIR score F4) a biopsy performed at any previous time is acceptable Participants who have cirrhosis must have an hepatic imaging procedure (ultrasound, computed tomography [CT] scan or magnetic resonance imaging [MRI]) within 6 months prior to the Screening visit (or between Screening and Day 1) with no findings suspicious for hepatocellular carcinoma Participant must have a body mass index (BMI) >= 18 Kilogram per meter^2 (kg/m^2) Participant must be treatment naive (that is, have not received prior treatment for HCV with any approved or investigational drug) Exclusion Criteria: Participant has co-infection with HCV of another genotype; a) Participant who has HCV genotype 1b has coinfection with HCV of a genotype other than genotype 1b Chronic HCV genotype 1b-infected participant who has the presence of genetic variants coding for the NS5A-Y93H and/or L31M/V amino acid substitutions at Screening Participant has evidence of current or previous episodes of hepatic decompensation (including controlled or uncontrolled ascites, bleeding varices or hepatic encephalopathy) Participant has chronic liver disease of a non-HCV etiology (including but not limited to hemochromatosis, Wilson's disease, alfa 1-antitrypsin deficiency, cholangitis, drug- or alcohol-related liver disease, primary biliary cirrhosis) Participant has any other uncontrolled clinically significant disease or clinically significant findings during Screening that in the opinion of the investigator could compromise the participants' safety or could interfere with the participant participating in and completing the study Participant has coinfection with hepatitis A or hepatitis B virus (hepatitis A antibody immunoglobulin M [IgM] or hepatitis B surface antigen [HBsAg] positive at Screening) Participant has received a solid organ transplant

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Simeprevir + Daclatasvir<br>Participants who have Hepatitis C virus (HCV) genotype 1b infection with advanced fibrosis or compensated cirrhosis (METAVIR F3/F4) will receive simeprevir 150 milligram (mg) capsule and daclatasvir 60 mg tablet orally once daily for 12 or 24 weeks. | Drug: Simeprevir<br>* Simeprevir 150 mg oral capsule will be administered once daily for 12 or 24 weeks.<br>Drug: Daclatasvir<br>* Daclatasvir 60 mg oral tablet will be administered once daily for 12 or 24 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Sustained Virologic Response 12 Weeks After End of Study Drug Treatment (SVR12) | Participants were considered to have reached SVR12, if 12 weeks after the actual end of treatment (EOT), hepatitis C virus (HCV) ribonucleic acid (RNA) was less than lower limit of quantification (<LLOQ) (detectable or undetectable). | At 12 weeks after end of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Sustained Virologic Response 4 Weeks After End of Study Drug Treatment (SVR4) | Participants were considered to have reached SVR4, if 4 weeks after the actual EOT, HCV RNA was <LLOQ (detectable or undetectable). | At 4 weeks after actual EOT | 
| Percentage of Participants With SVR 24 Weeks After End of Study Drug Treatment (SVR 24) | Participants were considered to have reached SVR24, if 24 weeks after the actual EOT, HCV RNA was <LLOQ (detectable or undetectable). | At 24 weeks after actual EOT | 
| Percentage of Participants With On-treatment Failure | Participants were considered on-treatment failures if they did not achieve SVR12 and had (confirmed) detectable HCV RNA, ie, <LLOQ detectable or greater than equal to (>=) LLOQ at EOT. | Up to Week 24 after actual EOT | 
| Number of Participants With Viral Breakthrough | Participants were considered to have had viral breakthrough if they had a confirmed greater than (>) 1.0 log10 international units/milliliter (IU/mL) increase in HCV RNA from nadir OR confirmed HCV RNA >100 IU/mL while previously having achieved HCV RNA <LLOQ when on study treatment. | Up to Week 24 | 
| Number of Participants With Viral Relapse | Participants were considered to have had viral relapse if they did not achieve SVR12 and met the following conditions: had HCV RNA <LLOQ (undetectable) at EOT and had HCV RNA >=LLOQ during the follow-up period. | Up to Week 24 after actual EOT | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatitis C Chronic, Simeprevir, Daclatasvir