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

Primary Purpose

Chronic Hepatitis C, Genotype 4 Chronic Hepatitis C

Status

Completed

Phase

Phase 3

Locations

Spain

Study Type

Interventional

Intervention

Simeprevir

Sofosbuvir

About this trial

This is an interventional treatment trial for Chronic Hepatitis C focused on measuring Chronic hepatitis C, Genotype 4 chronic hepatitis C, Simeprevir, Sofosbuvir

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Simeprevir and Sofosbuvir

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

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.

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.

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.

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.

Full Information

NCT ID

NCT02250807

First Posted

September 24, 2014

Last Updated

September 28, 2016

Sponsor

Janssen R&D Ireland

1. Study Identification

Unique Protocol Identification Number

NCT02250807

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2016

Overall Recruitment Status

Completed

Study Start Date

January 2015 (undefined)

Primary Completion Date

December 2015 (Actual)

Study Completion Date

December 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Janssen R&D Ireland

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chronic Hepatitis C, Genotype 4 Chronic Hepatitis C

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

40 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Simeprevir and Sofosbuvir

Arm Type

Experimental

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Simeprevir

Other Intervention Name(s)

TMC435

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Sofosbuvir

Intervention Description

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

Primary Outcome Measure Information:

Title

Percentage of Participants With Sustained Virologic Response 12 Weeks After End of Treatment (EOT) (SVR12)

Description

Time Frame

12 weeks after EOT

Secondary Outcome Measure Information:

Title

Percentage of Participants With Sustained Virologic Response 4 Weeks After End of Therapy (SVR4)

Description

Time Frame

4 weeks after EOT

Title

Percentage of Participants With Sustained Virologic Response 24 Weeks After End of Therapy (SVR24)

Description

Time Frame

At 24 weeks after EOT

Title

Percentage of Participants With On-treatment Virologic Response of Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)

Description

Percentage of participants with HCV RNA less than (<) 15 IU/mL undetectable or detectable or detectable /undetectable at specific time points were observed.

Time Frame

Week 2, 3, 4, 12 and EOT

Title

Percentage of Participants With On-Treatment Failure

Description

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)

Title

Percentage of Participants With Viral Breakthrough

Description

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.

Time Frame

Up to follow-up Week 24

Title

Percentage of Participants With Viral Relapse

Description

Time Frame

Up to follow-up week 24

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Janssen R&D Ireland Clinical Trials

Organizational Affiliation

Janssen R&D Ireland

Official's Role

Study Director

Facility Information:

City

Badalona

Country

Spain

City

Barcelona

Country

Spain

City

Madrid

Country

Spain

City

Santander N/A

Country

Spain

City

Sevilla N/A

Country

Spain

City

Sevilla

Country

Spain

City

Valencia

Country

Spain

12. IPD Sharing Statement

Citations:

PubMed Identifier

27896822

Citation

Buti M, Calleja JL, Lens S, Diago M, Ortega E, Crespo J, Planas R, Romero-Gomez M, Rodriguez FG, Pascasio JM, Fevery B, Kurland D, Corbett C, Kalmeijer R, Jessner W. Simeprevir in combination with sofosbuvir in treatment-naive and -experienced patients with hepatitis C virus genotype 4 infection: a Phase III, open-label, single-arm study (PLUTO). Aliment Pharmacol Ther. 2017 Feb;45(3):468-475. doi: 10.1111/apt.13883. Epub 2016 Nov 29.

Results Reference

derived

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

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