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

Phase 3

Completed

• Conditions: Genotype 4 Chronic Hepatitis C; Chronic Hepatitis C
• Interventions: Drug: Simeprevir; Drug: Sofosbuvir

• Registration Number: NCT02250807
• Lead Sponsor: Janssen R&D Ireland

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.

Study Timeline

• Study First Submitted: 2014-09-24
• Study First Submitted QC: 2014-09-24
• Study First Posted: 2014-09-26
• Study Start: 2015-01
• Primary Completion: 2015-12
• Study Completion: 2015-12
• Status Verified: 2016-09
• Results First Submitted: 2016-09-28
• Results First Submitted QC: 2016-09-28
• Last Update Submitted: 2016-09-28
• Results First Posted: 2016-11-17
• Last Update Posted: 2016-11-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 40

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Simeprevir and Sofosbuvir	Simeprevir	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.
Simeprevir and Sofosbuvir	Sofosbuvir	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.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Sustained Virologic Response 12 Weeks After End of Treatment (EOT) (SVR12)	12 weeks after EOT	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.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With On-treatment Virologic Response of Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)	Week 2, 3, 4, 12 and EOT	Percentage of participants with HCV RNA less than (\<) 15 IU/mL undetectable or detectable or detectable /undetectable at specific time points were observed.
Percentage of Participants With Viral Breakthrough	Up to follow-up Week 24	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.
Percentage of Participants With Sustained Virologic Response 24 Weeks After End of Therapy (SVR24)	At 24 weeks after EOT	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.
Percentage of Participants With Sustained Virologic Response 4 Weeks After End of Therapy (SVR4)	4 weeks after EOT	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.
Percentage of Participants With Viral Relapse	Up to follow-up week 24	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.
Percentage of Participants With On-Treatment Failure	through 12 weeks (EOT)	Participants were considered on-treatment failures if they have at EOT (confirmed) detectable HCV RNA, i.e., \<LLOQ detectable or \>=LLOQ.