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

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

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02250807

Enrollment

Registered

2014-09-26

Start date

2015-01-31

Completion date

2015-12-31

Last updated

2016-11-17

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Chronic Hepatitis C, Genotype 4 Chronic Hepatitis C

Keywords

Chronic hepatitis C, Genotype 4 chronic hepatitis C, Simeprevir, Sofosbuvir

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.

Interventions

DRUGSimeprevir

Subjects will receive oral capsule of Simeprevir 150 mg, once a day from Day 1 up to Week 12.

DRUGSofosbuvir

Subjects will receive oral tablet of sofosbuvir 400 mg, once a day from Day 1 up to Week 12.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 70 Years

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
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 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 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 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 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.

Countries

Spain

Participant flow

Participants by arm

Arm	Count
SMV+SOF 12 Weeks Participants received oral capsule of simeprevir (SMV) 150 milligram (mg) and an oral tablet of sofosbuvir (SOF) 400 mg, once a day from Day 1 through Week 12.	40
Total	40

Baseline characteristics

Characteristic	SMV+SOF 12 Weeks
Age, Continuous	51 years
Sex: Female, Male Female	11 Participants
Sex: Female, Male Male	29 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	17 / 40
serious Total, serious adverse events	0 / 40

Outcome results

Primary

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.

Time frame: 12 weeks after EOT

Population: Intent-to-treat (ITT) population included all randomized participants who received at least 1 dose of study medication (SMV and/or SOF).

Arm	Measure	Value (NUMBER)
SMV+SOF 12 Weeks	Percentage of Participants With Sustained Virologic Response 12 Weeks After End of Treatment (EOT) (SVR12)	100 percentage of participants

Secondary

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.

Time frame: through 12 weeks (EOT)