Back to resultsEfficacy and Safety Study of Simeprevir in Combination With Sofosbuvir in Participants With Genotype 1 Chronic Hepatitis C Virus Infection and Cirrhosis
Primary Purpose
Hepatitis C Virus Infection
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Simeprevir
Sofosbuvir
Sponsored by
About this trial
This is an interventional treatment trial for Hepatitis C Virus Infection focused on measuring Hepatitis C Virus Infection, Simeprevir, Sofosbuvir, HCV, Cirrhosis
Eligibility Criteria
Inclusion Criteria:
- Hepatitis C virus (HCV) genotype 1 infection (confirmed at screening).
- HCV ribonucleic acid (RNA) 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
- Participants must have an hepatic imaging procedure (ultrasound, computerized tomography scan or magnetic resonance imaging scan) within 6 months prior to the screening visit (or between screening and Day 1) with no findings suspicious for hepatocellular carcinoma
- Participant must be willing and able to comply with the protocol requirements
- Participants with liver cirrhosis
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 1
- 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
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Arm 1 (Simeprevir/Sofosbuvir)
Arm Description
100 participants will receive 1 capsule of 150 mg simeprevir and 1 tablet of 400 mg sofosbuvir orally (by mouth) once daily for 12 weeks.
Outcomes
Primary Outcome Measures
Percentage of Participants With a Sustained Virologic Response (SVR) 12 Weeks After the Actual End of Treatment (EOT)
Participants with hepatitis C virus (HCV) ribonucleic acid (RNA) less than (<) 25 international unit per milliliter (IU/mL) (detectable or undetectable) at 12 weeks after the actual end of treatment.
Secondary Outcome Measures
Percentage of Participants With a Sustained Virologic Response (SVR) 4 Weeks After the Actual End of Treatment (EOT)
Participants with hepatitis C virus (HCV) ribonucleic acid (RNA) less than (<) 25 international unit per milliliter (IU/mL) (detectable or undetectable) at 4 weeks after the actual end of treatment.
Percentage of Participants With a Sustained Virologic Response (SVR) 24 Weeks After the Actual End of Treatment (EOT)
Participants with hepatitis C virus (HCV) ribonucleic acid (RNA) less than (<) 25 international unit per milliliter (IU/mL) (detectable or undetectable) at 24 weeks after the actual end of treatment.
Percentage of Participants With On-treatment Virologic Response
On-treatment 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.
Percentage of Participants With On-treatment Failure
On-treatment failure is defined as participants who do not achieve SVR12 and with confirmed detectable HCV RNA at the actual end of study drug treatment.
Percentage of Participants With Viral Breakthrough
Viral breakthrough was defined as confirmed greater than (>) 1 log10 increase in HCV RNA from nadir or confirmed HCV RNA >100 IU/mL in participants who had previously achieved HCV RNA < LLOQ (25 IU/mL).
Percentage of Participants With Viral Relapse
Viral relapse was defined as participants who did not achieve SVR12 and had HCV RNA < LLOQ (25 IU/mL) undetectable at EOT and had HCV RNA >= LLOQ (25 IU/mL) during the follow-up period.
Change From Baseline in Hepatitis C Symptom and Impact Questionnaire Version 4 (HCV-SIQv4) Overall Body System Score (OBSS) up to Follow-up Week 12
The HCV-SIQv4 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.
Change From Baseline in Fatigue Severity Score (FSS) up to 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 7-point 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.
Percentage of Participants With Depression by Using Center for Epidemiologic Studies Depression Scale (CES-D)
The CES-D Scale assessed how often during the past week participants experienced 20 symptoms commonly associated with major depression. The CES-D scores range from 0 (no symptoms) to 60 (all 20 symptoms most or all of the time during the past 5 to 7 days). The CES-D scores between 16 and 23 points indicate mild to moderate depressive illness while CES-D scores >=23 indicate probable major depressive illness.
Change From Baseline in EuroQol 5 Dimension Questionnaire (EQ-5D) up to Follow-up Week 24
The EQ-5D questionnaire was a brief, generic health-related quality of life (HRQOL) assessment that could also be used to incorporate participant preferences into health economic evaluations. The EQ-5D questionnaire assessed 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).
Number of Participants Not Achieving SVR Showing Emerging Mutation at Time of Failure in HCV NS3/4A Sequence and NS5B up to Follow-up Week 24
Sequencing of the HCV nonstructural protein 3/4A (NS3/4A) and nonstructural protein 5B (NS5B) genes was done to identify pre-existing sequence polymorphisms and characterize emerging HCV viral variants in participants not achieving SVR. Sequencing data is available for 16 participants.
Full Information
NCT ID
NCT02114151
First Posted
April 2, 2014
Last Updated
March 7, 2016
Sponsor
Janssen Infectious Diseases BVBA
1. Study Identification
Unique Protocol Identification Number
NCT02114151
Brief Title
Efficacy and Safety Study of Simeprevir in Combination With Sofosbuvir in Participants With Genotype 1 Chronic Hepatitis C Virus Infection and Cirrhosis
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-Naïve or -Experienced Subjects With Chronic Genotype 1 Hepatitis C Virus Infection and Cirrhosis
Study Type
Interventional
2. Study Status
Record Verification Date
March 2016
Overall Recruitment Status
Completed
Study Start Date
April 2014 (undefined)
Primary Completion Date
January 2015 (Actual)
Study Completion Date
April 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen Infectious Diseases BVBA
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of the study is to investigate the efficacy and safety of 12 weeks of simeprevir (150 mg qd) in combination with sofosbuvir (400 mg qd) in chronic hepatitis C virus (HCV) genotype 1 infected men and women with cirrhosis who are HCV treatment-naïve or treatment-experienced.
Detailed Description
This is a open-label (all people know the identity of the intervention), single arm, multicenter study. The study will consist of a screening phase up to 4 weeks, open-label treatment phase of 12 weeks, and post-treatment follow up phase up to 24 weeks after end of treatment. Approximately 100 participants will receive 150 mg simeprevir in combination with 400 mg sofosbuvir once dailyfor 12 weeks. 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 40 weeks.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis C Virus Infection
Keywords
Hepatitis C Virus Infection, Simeprevir, Sofosbuvir, HCV, Cirrhosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
103 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm 1 (Simeprevir/Sofosbuvir)
Arm Type
Experimental
Arm Description
100 participants will receive 1 capsule of 150 mg simeprevir and 1 tablet of 400 mg sofosbuvir orally (by mouth) once daily for 12 weeks.
Intervention Type
Drug
Intervention Name(s)
Simeprevir
Intervention Description
100 participants will receive 1 capsule of 150 mg orally once daily for 12 weeks.
Intervention Type
Drug
Intervention Name(s)
Sofosbuvir
Intervention Description
100 participants will receive 1 tablet of 400 mg sofosbuvir orally once daily for 12 weeks.
Primary Outcome Measure Information:
Title
Percentage of Participants With a Sustained Virologic Response (SVR) 12 Weeks After the Actual End of Treatment (EOT)
Description
Participants with hepatitis C virus (HCV) ribonucleic acid (RNA) less than (<) 25 international unit per milliliter (IU/mL) (detectable or undetectable) at 12 weeks after the actual end of treatment.
Time Frame
Week 24
Secondary Outcome Measure Information:
Title
Percentage of Participants With a Sustained Virologic Response (SVR) 4 Weeks After the Actual End of Treatment (EOT)
Description
Participants with hepatitis C virus (HCV) ribonucleic acid (RNA) less than (<) 25 international unit per milliliter (IU/mL) (detectable or undetectable) at 4 weeks after the actual end of treatment.
Time Frame
Week 16
Title
Percentage of Participants With a Sustained Virologic Response (SVR) 24 Weeks After the Actual End of Treatment (EOT)
Description
Participants with hepatitis C virus (HCV) ribonucleic acid (RNA) less than (<) 25 international unit per milliliter (IU/mL) (detectable or undetectable) at 24 weeks after the actual end of treatment.
Time Frame
Week 36
Title
Percentage of Participants With On-treatment Virologic Response
Description
On-treatment 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.
Time Frame
Week 2, 4 and End of Treatment (Week 12)
Title
Percentage of Participants With On-treatment Failure
Description
On-treatment failure is defined as participants who do not achieve SVR12 and with confirmed detectable HCV RNA at the actual end of study drug treatment.
Time Frame
Week 12
Title
Percentage of Participants With Viral Breakthrough
Description
Viral breakthrough was defined as confirmed greater than (>) 1 log10 increase in HCV RNA from nadir or confirmed HCV RNA >100 IU/mL in participants who had previously achieved HCV RNA < LLOQ (25 IU/mL).
Time Frame
Up to End of Treatment (Week 12)
Title
Percentage of Participants With Viral Relapse
Description
Viral relapse was defined as participants who did not achieve SVR12 and had HCV RNA < LLOQ (25 IU/mL) undetectable at EOT and had HCV RNA >= LLOQ (25 IU/mL) during the follow-up period.
Time Frame
During the Follow-up (Week 24)
Title
Change From Baseline in Hepatitis C Symptom and Impact Questionnaire Version 4 (HCV-SIQv4) Overall Body System Score (OBSS) up to Follow-up Week 12
Description
The HCV-SIQv4 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.
Time Frame
Baseline, Week 4, Week 12 and Follow-Up Week 12
Title
Change From Baseline in Fatigue Severity Score (FSS) up to Follow-up Week 24
Description
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 7-point 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.
Time Frame
Baseline, Week 12, Follow-up Week 12 and 24
Title
Percentage of Participants With Depression by Using Center for Epidemiologic Studies Depression Scale (CES-D)
Description
The CES-D Scale assessed how often during the past week participants experienced 20 symptoms commonly associated with major depression. The CES-D scores range from 0 (no symptoms) to 60 (all 20 symptoms most or all of the time during the past 5 to 7 days). The CES-D scores between 16 and 23 points indicate mild to moderate depressive illness while CES-D scores >=23 indicate probable major depressive illness.
Time Frame
Baseline, Week 12, Follow-up Week 12 and 24
Title
Change From Baseline in EuroQol 5 Dimension Questionnaire (EQ-5D) up to Follow-up Week 24
Description
The EQ-5D questionnaire was a brief, generic health-related quality of life (HRQOL) assessment that could also be used to incorporate participant preferences into health economic evaluations. The EQ-5D questionnaire assessed 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).
Time Frame
Baseline, Follow-up Week 12 and 24
Title
Number of Participants Not Achieving SVR Showing Emerging Mutation at Time of Failure in HCV NS3/4A Sequence and NS5B up to Follow-up Week 24
Description
Sequencing of the HCV nonstructural protein 3/4A (NS3/4A) and nonstructural protein 5B (NS5B) genes was done to identify pre-existing sequence polymorphisms and characterize emerging HCV viral variants in participants not achieving SVR. Sequencing data is available for 16 participants.
Time Frame
Baseline, Day 3, Week 1, 2, 3, 4, 8, 12, Follow-up Week 4, 12 and 24
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Hepatitis C virus (HCV) genotype 1 infection (confirmed at screening).
HCV ribonucleic acid (RNA) 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
Participants must have an hepatic imaging procedure (ultrasound, computerized tomography scan or magnetic resonance imaging scan) within 6 months prior to the screening visit (or between screening and Day 1) with no findings suspicious for hepatocellular carcinoma
Participant must be willing and able to comply with the protocol requirements
Participants with liver cirrhosis
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 1
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen Infectious Diseases BVBA Clinical Trial
Organizational Affiliation
Janssen Infectious Diseases BVBA
Official's Role
Study Director
Facility Information:
City
Dothan
State/Province
Alabama
Country
United States
City
Bakersfield
State/Province
California
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United States
City
Chula Vista
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California
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United States
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Los Angeles
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California
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United States
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San Diego
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California
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United States
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Englewood
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Colorado
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United States
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Bradenton
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Florida
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United States
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Lauderdale Lakes
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Florida
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Maitland
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Miami
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Orlando
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Wellington
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United States
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Atlanta
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Georgia
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United States
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Columbus
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Georgia
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United States
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Marietta
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Georgia
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United States
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Jackson
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Mississippi
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Kansas City
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Missouri
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Hillsborough
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New Jersey
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United States
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Vineland
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New Jersey
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New York
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New York
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United States
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Asheville
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North Carolina
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United States
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Winston Salem
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North Carolina
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United States
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East Greenwich
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Rhode Island
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United States
City
Providence
State/Province
Rhode Island
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United States
City
Greer
State/Province
South Carolina
Country
United States
City
Germantown
State/Province
Tennessee
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United States
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Knoxville
State/Province
Tennessee
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United States
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Nashville
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Tennessee
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United States
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Arlington
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Texas
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United States
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Austin
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Texas
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United States
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San Antonio
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Texas
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United States
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Norfolk
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Virginia
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United States
City
Vancouver
State/Province
British Columbia
Country
Canada
City
Montreal
State/Province
Quebec
Country
Canada
12. IPD Sharing Statement
Learn more about this trial
Efficacy and Safety Study of Simeprevir in Combination With Sofosbuvir in Participants With Genotype 1 Chronic Hepatitis C Virus Infection and Cirrhosis
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