Efficacy and Safety Study of Simeprevir in Combination With Sofosbuvir in Subjects With Chronic Genotype 4 Hepatitis C Virus Infection

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to show superiority of simeprevir (SMV) in combination with sofosbuvir for 12 weeks versus a historical control. Historical control will be a composite of the observed historical sustained virological response at Week 12 (SVR12) rates of SMV in combination with (pegylated) interferon (PegIFN)/ribavirin (RBV) of the subpopulations in study HPC3011 (NCT01567735) and will depend on the percentage of treatment-naive, prior relapser, prior non-responder, interferon (IFN)-intolerant and other subjects enrolled in this study.

Detailed Description
-----------------
This is a Phase 3, open-label (all people know the identity of the intervention), single-arm, multicenter study (conducted at multiple sites). The study consists of 3 periods: a Screening period (up to 4 weeks), Treatment period (12 Weeks) and Post treatment follow-up period (until 24 weeks after end of treatment). The duration of the subjects' participation will be approximately 40 weeks. In the treatment period subjects will receive oral capsule simeprevir along with oral tablet sofosbuvir once daily for 12 weeks. Primarily efficacy will be evaluated as percentage of subjects with sustained virologic response at Week 12 after the end of treatment. Subjects' safety will be monitored throughout the study.

Official Title
-----------------
A Phase 3, Multicenter, Open-Label, Single-Arm Study to Investigate the Efficacy and Safety of a 12-Week Regimen of Simeprevir in Combination With Sofosbuvir in Treatment-Naive or -Experienced Subjects With Chronic Genotype 4 Hepatitis C Virus Infection

Conditions
-----------------
Chronic Hepatitis C, Genotype 4 Chronic Hepatitis C

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects with confirmed hepatitis C virus (HCV) with HCV RNA greater than (>) 10000 international unit per milliliter (IU/mL) Subjects who are treatment naive or treatment-experienced. Subjects must have documentation of a liver biopsy or fibroscan or agree to have one during screening Subjects with cirrhosis must have an hepatic imaging procedure (ultrasound, CT scan or magnetic resonance imaging [MRI]) within 6 months before the screening visit (or during the screening period) with no findings suspicious for hepatocellular carcinoma (HCC) Women of childbearing potential or men with a female partner of childbearing potential must agree to use an effective form of contraception, or not be heterosexually active, or of nonchildbearing potential Exclusion Criteria: Evidence of clinical hepatic decompensation Any liver disease of non-HCV etiology Subjects with a past history of treatment with an approved or investigational DAA 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) Infection/co-infection with HCV non-genotype 4

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Simeprevir and Sofosbuvir<br>Subjects will receive oral capsule of Simeprevir 150 milligram (mg) along with oral tablet of sofosbuvir 400 mg, once a day from Day 1 up to Week 12. | Drug: Simeprevir<br>* Subjects will receive oral capsule of Simeprevir 150 mg, once a day from Day 1 up to Week 12.<br>* Other names: TMC435;Drug: Sofosbuvir<br>* Subjects will receive oral tablet of sofosbuvir 400 mg, once a day from Day 1 up to Week 12.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Sustained Virologic Response 12 Weeks After End of Treatment (EOT) (SVR12) | SVR12 is defined as the percentage of participants with hepatitis C virus ribonucleic acid (HCV RNA) less than (<) lower limit of quantification (LLOQ; 15 international unit per milliliter [IU/mL]) detectable or undetectable 12 weeks after actual EOT. | 12 weeks after EOT | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Sustained Virologic Response 4 Weeks After End of Therapy (SVR4) | SVR4 is defined as the percentage of participants with hepatitis C virus ribonucleic acid (HCV RNA) less than (<) lower limit of quantification (LLOQ; 15 international unit per milliliter [IU/mL]) detectable or undetectable 4 weeks after actual EOT. | 4 weeks after EOT | 
| Percentage of Participants With Sustained Virologic Response 24 Weeks After End of Therapy (SVR24) | Participants were considered to have reached SVR24, if at the time point of SVR24 (that is [i.e.], 24 weeks after the end of treatment [EOT]) the following condition has been met: HCV RNA < lower limit of quantification (LLOQ), i.e., 15 IU/mL, detectable or undetectable. | At 24 weeks after EOT | 
| Percentage of Participants With On-treatment Virologic Response of Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) | Percentage of participants with HCV RNA less than (<) 15 IU/mL undetectable or detectable or detectable /undetectable at specific time points were observed. | Week 2, 3, 4, 12 and EOT | 
| Percentage of Participants With On-Treatment Failure | Participants were considered on-treatment failures if they have at EOT (confirmed) detectable HCV RNA, i.e., <LLOQ detectable or >=LLOQ. | through 12 weeks (EOT) | 
| Percentage of Participants With Viral Breakthrough | Participants with confirmed >1.0 log10 increase in HCV RNA from nadir or confirmed HCV RNA >100 IU/mL in participants who had previously achieved HCV RNA <LLOQ. | Up to follow-up Week 24 | 
| Percentage of Participants With Viral Relapse | Participants were considered to have viral relapse if they did not achieve SVR12 and meet the following conditions: 1) at EOT, HCV RNA less than (<)LLOQ, undetectable, and 2) during the follow-up period, HCV RNA greater than or equal to (>=)LLOQ. | Up to follow-up week 24 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Chronic hepatitis C, Genotype 4 chronic hepatitis C, Simeprevir, Sofosbuvir