Efficacy and Safety Study of Simeprevir in Combination With Sofosbuvir in Participants With Chronic Hepatitis C Virus Infection Without Cirrhosis

March 14, 2016 updated by: Janssen Infectious Diseases BVBA

A Phase 3, Multicenter, Randomized, Open-Label Study to Investigate the Efficacy and Safety of a 12- or 8-Week Treatment Regimen of Simeprevir in Combination With Sofosbuvir in Treatment-Naïve and -Experienced Subjects With Chronic Genotype 1 Hepatitis C Virus Infection Without Cirrhosis

The purpose of the study is to evaluate the efficacy and safety of a treatment regimen of 12 weeks or 8 weeks of simeprevir in combination with sofosbuvir in chronic hepatitis C virus (HCV) genotype 1 infected men and women without cirrhosis who are HCV treatment-naïve or treatment-experienced.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is a randomized (the study medication is assigned by chance), open-label (all people know the identity of the intervention), multicenter study. The study will consist of a screening phase up to 6 weeks, open-label treatment phase of 8 weeks or 12 weeks, and post-treatment follow up phase up to 24 weeks after end of treatment. Approximately 300 participants will be randomly allocated in a 1:1 ratio to receive 150 mg simeprevir in combination with 400 mg sofosbuvir once daily either for 12 weeks (Arm 1) or 8 weeks (Arm 2). Safety evaluations will include assessment of adverse events, clinical laboratory tests, vital signs, and physical examination. The maximum study duration for each participant will be approximately 42 weeks.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
310

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • British Columbia
      • Vancouver, British Columbia, Canada
    • Quebec
      • Montreal, Quebec, Canada
  • United States
    • Alabama
      • Dothan, Alabama, United States
    • California
      • Bakersfield, California, United States
      • Chula Vista, California, United States
      • Los Angeles, California, United States
      • San Diego, California, United States
    • Colorado
      • Englewood, Colorado, United States
    • Florida
      • Bradenton, Florida, United States
      • Jacksonville, Florida, United States
      • Lauderdale Lakes, Florida, United States
      • Maitland, Florida, United States
      • Miami, Florida, United States
      • Orlando, Florida, United States
      • Wellington, Florida, United States
      • Zephyrhills, Florida, United States
    • Georgia
      • Atlanta, Georgia, United States
      • Columbus, Georgia, United States
      • Marietta, Georgia, United States
    • Indiana
      • Indianapolis, Indiana, United States
    • Mississippi
      • Jackson, Mississippi, United States
    • Missouri
      • Kansas City, Missouri, United States
    • New Jersey
      • Hillsborough, New Jersey, United States
      • Vineland, New Jersey, United States
    • New York
      • Manhasset, New York, United States
      • New York, New York, United States
      • Ny, New York, United States
    • North Carolina
      • Asheville, North Carolina, United States
      • Winston Salem, North Carolina, United States
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States
    • Rhode Island
      • East Greenwich, Rhode Island, United States
      • Providence, Rhode Island, United States
    • South Carolina
      • Greer, South Carolina, United States
    • Tennessee
      • Germantown, Tennessee, United States
      • Knoxville, Tennessee, United States
      • Nashville, Tennessee, United States
    • Texas
      • Arlington, Texas, United States
      • Austin, Texas, United States
      • San Antonio, Texas, United States
    • Virginia
      • Falls Church, Virginia, United States
      • Norfolk, Virginia, United States

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Hepatitis C virus (HCV) genotype 1a or 1b infection confirmed before randomization
  • Documentation of the presence or absence of a NS3 Q80K polymorphism in HCV genotype 1a infected participants before randomization
  • Documentation of the IL28B genotype before randomization
  • HCV ribonucleic acid level greater than 10,000 IU/mL at screening
  • Treatment-experienced participants must have at least 1 documented previous course of interferon-based regimen with or without ribavirin
  • Absence of cirrhosis in participants

Exclusion Criteria:

  • Evidence of clinical hepatic decompensation (history or current evidence of ascites, bleeding varices or hepatic encephalopathy)
  • Infection/co-infection with HCV non-genotype 1a or 1b
  • 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)
  • Co-infection with hepatitis-B virus (hepatitis-B-surface-antigen positive)
  • Previously been treated with any direct acting anti-HCV agent (approved or investigational) for chronic HCV infection

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Arm 1 (Simeprevir/Sofosbuvir)
150 participants will receive 1 capsule of 150 mg simeprevir and 1 tablet of 400 mg sofosbuvir orally (by mouth) once daily for 12 weeks.
Drug: Simeprevir
150 participants will receive 1 capsule of 150 mg simeprevir orally once daily for 12 weeks in Arm 1.
Drug: Simeprevir
150 participants will receive 1 capsule of 150 mg simeprevir orally once daily for 8 weeks in Arm 2
Drug: Sofosbuvir
150 participants will receive 1 tablet of 400 mg sofosbuvir orally once daily for 12 weeks in Arm 1.
Drug: Sofosbuvir
150 participants will receive 1 tablet of 400 mg sofosbuvir orally once daily for 8 weeks in Arm 2.
Experimental: Arm 2 (Simeprevir/Sofosbuvir)
150 participants will receive 1 capsule of 150 mg simeprevir and 1 tablet of 400 mg sofosbuvir orally once daily for 8 weeks.
Drug: Simeprevir
150 participants will receive 1 capsule of 150 mg simeprevir orally once daily for 12 weeks in Arm 1.
Drug: Simeprevir
150 participants will receive 1 capsule of 150 mg simeprevir orally once daily for 8 weeks in Arm 2
Drug: Sofosbuvir
150 participants will receive 1 tablet of 400 mg sofosbuvir orally once daily for 12 weeks in Arm 1.
Drug: Sofosbuvir
150 participants will receive 1 tablet of 400 mg sofosbuvir orally once daily for 8 weeks in Arm 2.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Percentage of Participants Achieving a Sustained Virologic Response 12 Weeks After the Actual End of Treatment (SVR12)
Time Frame: 12 weeks after the end of treatment (EOT) (Week 20 or Week 24)
Participants considered to have achieved SVR12, if the hepatitis C virus ribonucleic acid (HCV RNA) is less than (<) lower limit of quantification (LLOQ; 25 international unit per milliliter [IU/mL]) detectable or undetectable at 12 weeks after the actual end of study drug treatment.
12 weeks after the end of treatment (EOT) (Week 20 or Week 24)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Percentage of Participants Achieving a Sustained Virologic Response 4 Weeks After the Actual End of Treatment (SVR4)
Time Frame: 4 weeks after the end of treatment (EOT) (Week 12 or Week 16)
Participants considered to have achieved SVR4, if the hepatitis C virus ribonucleic acid (HCV RNA) is less than (<) lower limit of quantification (LLOQ; 25 international unit per milliliter [IU/mL]) detectable or undetectable at 4 weeks after the actual end of study drug treatment.
4 weeks after the end of treatment (EOT) (Week 12 or Week 16)
Percentage of Participants Achieving a Sustained Virologic Response 24 Weeks After the Actual End of Treatment (SVR24)
Time Frame: 24 weeks after the end of treatment (EOT) (Week 32 or Week 36)
Participants considered to have achieved SVR24, if the hepatitis C virus ribonucleic acid (HCV RNA) is less than (<) lower limit of quantification (LLOQ; 25 international unit per milliliter [IU/mL]) detectable or undetectable at 24 weeks after the Actual end of study drug treatment.
24 weeks after the end of treatment (EOT) (Week 32 or Week 36)
Percentage of Participants Achieving a On-treatment Virologic Response
Time Frame: Day 14, Day 28, End of treatment (Week 8 or Week 12)
Ontreatment virologic response was determined by HCV RNA results satisfying a specified threshold. <LLOQ undetectable was considered as threshold at any time point. The LLOQ value is 25 IU/mL. EOT=End of Treatment.
Day 14, Day 28, End of treatment (Week 8 or Week 12)
Percentage of Participants With Viral Breakthrough
Time Frame: Up to Week 24
Percentage of participants with greater than 1 log10 IU/mL increase in plasma Hepatitis C virus ribonucleic acid level from the lowest level reached (ie, lowest value measured in between baseline and current value), or a confirmed plasma HCV RNA level of greater than 100 IU/mL in participants whose plasma HCV RNA had previously been less than 25 IU/mL.
Up to Week 24
Percentage of Participants With Viral Relapse
Time Frame: Up to Week 24
Percentage of participants who did not achieve sustained virologic response 12, have less than 25 IU/mL undetectable plasma HCV RNA at end of treatment, and greater than or equal to 25 IU/mL plasma HCV RNA during the follow-up phase.
Up to Week 24
Change From Baseline in Hepatitis C Symptom and Impact Questionnaire 4 (HCV-SIQv4) Overall Body System Score (OBSS)
Time Frame: Baseline (Day 1), Week 4, Week 8, Week 12, Follow-up Week 4, Follow-up Week 12 and Follow-up Week 24
HCVSIQv4 OBSS was a self-administered questionnaire that contained 33 items: 29 questions developed to assess severity or frequency of symptoms associated with HCV or its treatment, 3 questions regarding the impact of symptoms on work/school attendance, and 1 question regarding the impact of symptoms on daily activities. A symptom severity score (the mean of responses to the 29 symptom items); each symptom score was transformed to have a range from 0 to 100 (most severe). Higher HCV SIQv4 scores indicates worse symptom severity, more time missed from work/school, and more impairment in daily activities, respectively.
Baseline (Day 1), Week 4, Week 8, Week 12, Follow-up Week 4, Follow-up Week 12 and Follow-up Week 24
Change From Baseline in Fatigue Severity Scale (FSS) Score up to Follow-up Week 24
Time Frame: Baseline (Day 1), Week 4, Week 8, Week 12, Follow-up Week 4, Follow-up Week 12 and Follow-up Week 24
The FSS was a self-administered questionnaire with 9 items developed to assess disabling fatigue that has been used extensively in studies of chronic HCV infection. Item responses were measured on a 7point Likert scale ranging from strongly disagree (1 point) to strongly agree (7 points). The 9 items were averaged to produce a total score; a lower total score indicates less severe fatigue. FSS scores have a range from 1 to 7 where higher scores indicate more severe fatigue.
Baseline (Day 1), Week 4, Week 8, Week 12, Follow-up Week 4, Follow-up Week 12 and Follow-up Week 24
Change From Baseline in Center for Epidemiologic Studies Depression Scale (CES-D) Scores
Time Frame: Baseline (Day 1), Week 4, Week 8, Week 12, Follow-up Week 4, Follow-up Week 12 and Follow-up Week 24
The CES-D scale assesses how often during the past week participants experienced 20 symptoms commonly associated with major depression. CES-D scores range from 0 (no symptoms) to 60 (all 20 symptoms most or all of the time during the past 5-7 days). The CES-D scores between 16 and 23 points indicate mild to moderate depressive illness while CES-D scores greater than or equal to 23 indicate probable major depressive illness.
Baseline (Day 1), Week 4, Week 8, Week 12, Follow-up Week 4, Follow-up Week 12 and Follow-up Week 24
Change From Baseline in EuroQol 5 Dimension (EQ-5D) Visual Analogue Scale
Time Frame: Baseline (Day 1), Week 4, Week 8, Week 12, Follow-up Week 4, Follow-up Week 12 and Follow-up Week 24
The EQ-5D questionnaire is a brief, generic health-related quality of life assessment (HRQOL) that can also be used to incorporate participant preferences into health economic evaluations. The EQ-5D questionnaire assesses HRQOL in terms of degree of limitation on 5 health dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) and as overall health using a "thermometer" visual analog scale with response options ranging from 0 (worst imaginable health) to 100 (best imaginable health). Lower scores indicate worsening.
Baseline (Day 1), Week 4, Week 8, Week 12, Follow-up Week 4, Follow-up Week 12 and Follow-up Week 24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Janssen Infectious Diseases BVBA

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 1, 2014

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 1, 2015

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 1, 2015

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 2, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 11, 2014

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 15, 2014

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 12, 2016

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 14, 2016

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CR103430
  • TMC435HPC3017 (Other Identifier: Janssen Infectious Diseases BVBA)

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