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

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ClinicalTrials.gov Identifier: NCT02114177
Recruitment Status : Completed
First Posted : April 15, 2014
Results First Posted : April 12, 2016
Last Update Posted : April 12, 2016
Sponsor:
Information provided by (Responsible Party):
Janssen Infectious Diseases BVBA

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Hepatitis C Virus Infection Drug: Simeprevir Drug: Sofosbuvir Phase 3

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 : Interventional  (Clinical Trial)
Actual Enrollment : 310 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : April 2014
Actual Primary Completion Date : January 2015
Actual Study Completion Date : April 2015

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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: Sofosbuvir
150 participants will receive 1 tablet of 400 mg sofosbuvir orally once daily for 12 weeks in Arm 1.

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 8 weeks in Arm 2

Drug: Sofosbuvir
150 participants will receive 1 tablet of 400 mg sofosbuvir orally once daily for 8 weeks in Arm 2.




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02114177


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Sponsors and Collaborators
Janssen Infectious Diseases BVBA
Investigators
Study Director: Janssen Infectious Diseases BVBA Clinical Trial Janssen Infectious Diseases BVBA

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Janssen Infectious Diseases BVBA
ClinicalTrials.gov Identifier: NCT02114177     History of Changes
Other Study ID Numbers: CR103430
TMC435HPC3017 ( Other Identifier: Janssen Infectious Diseases BVBA )
First Posted: April 15, 2014    Key Record Dates
Results First Posted: April 12, 2016
Last Update Posted: April 12, 2016
Last Verified: March 2016

Keywords provided by Janssen Infectious Diseases BVBA:
Hepatitis C Virus Infection
Simeprevir
Sofosbuvir
HCV
Cirrhosis

Additional relevant MeSH terms:
Infection
Communicable Diseases
Hepatitis
Hepatitis A
Hepatitis C
Fibrosis
Liver Cirrhosis
Virus Diseases
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Pathologic Processes
Sofosbuvir
Simeprevir
Antiviral Agents
Anti-Infective Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action