search
Back to results

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

Primary Purpose

Hepatitis C Virus Infection

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Simeprevir
Simeprevir
Sofosbuvir
Sofosbuvir
Sponsored by
Janssen Infectious Diseases BVBA
About
Eligibility
Locations
Arms
Outcomes
Full info

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

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

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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Arm 1 (Simeprevir/Sofosbuvir)

Arm 2 (Simeprevir/Sofosbuvir)

Arm Description

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.

150 participants will receive 1 capsule of 150 mg simeprevir and 1 tablet of 400 mg sofosbuvir orally once daily for 8 weeks.

Outcomes

Primary Outcome Measures

Percentage of Participants Achieving a Sustained Virologic Response 12 Weeks After the Actual End of Treatment (SVR12)
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

Percentage of Participants Achieving a Sustained Virologic Response 4 Weeks After the Actual End of Treatment (SVR4)
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.
Percentage of Participants Achieving a Sustained Virologic Response 24 Weeks After the Actual End of Treatment (SVR24)
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.
Percentage of Participants Achieving a On-treatment Virologic Response
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.
Percentage of Participants With Viral Breakthrough
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.
Percentage of Participants With Viral Relapse
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.
Change From Baseline in Hepatitis C Symptom and Impact Questionnaire 4 (HCV-SIQv4) Overall Body System Score (OBSS)
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.
Change From Baseline in Fatigue Severity Scale (FSS) Score 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 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.
Change From Baseline in Center for Epidemiologic Studies Depression Scale (CES-D) Scores
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.
Change From Baseline in EuroQol 5 Dimension (EQ-5D) Visual Analogue Scale
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.

Full Information

First Posted
April 2, 2014
Last Updated
March 14, 2016
Sponsor
Janssen Infectious Diseases BVBA
search

1. Study Identification

Unique Protocol Identification Number
NCT02114177
Brief Title
Efficacy and Safety Study of Simeprevir in Combination With Sofosbuvir in Participants With Chronic Hepatitis C Virus Infection Without Cirrhosis
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 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 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.
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.

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
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
310 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm 1 (Simeprevir/Sofosbuvir)
Arm Type
Experimental
Arm Description
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.
Arm Title
Arm 2 (Simeprevir/Sofosbuvir)
Arm Type
Experimental
Arm Description
150 participants will receive 1 capsule of 150 mg simeprevir and 1 tablet of 400 mg sofosbuvir orally once daily for 8 weeks.
Intervention Type
Drug
Intervention Name(s)
Simeprevir
Intervention Description
150 participants will receive 1 capsule of 150 mg simeprevir orally once daily for 12 weeks in Arm 1.
Intervention Type
Drug
Intervention Name(s)
Simeprevir
Intervention Description
150 participants will receive 1 capsule of 150 mg simeprevir orally once daily for 8 weeks in Arm 2
Intervention Type
Drug
Intervention Name(s)
Sofosbuvir
Intervention Description
150 participants will receive 1 tablet of 400 mg sofosbuvir orally once daily for 12 weeks in Arm 1.
Intervention Type
Drug
Intervention Name(s)
Sofosbuvir
Intervention Description
150 participants will receive 1 tablet of 400 mg sofosbuvir orally once daily for 8 weeks in Arm 2.
Primary Outcome Measure Information:
Title
Percentage of Participants Achieving a Sustained Virologic Response 12 Weeks After the Actual End of Treatment (SVR12)
Description
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.
Time Frame
12 weeks after the end of treatment (EOT) (Week 20 or Week 24)
Secondary Outcome Measure Information:
Title
Percentage of Participants Achieving a Sustained Virologic Response 4 Weeks After the Actual End of Treatment (SVR4)
Description
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.
Time Frame
4 weeks after the end of treatment (EOT) (Week 12 or Week 16)
Title
Percentage of Participants Achieving a Sustained Virologic Response 24 Weeks After the Actual End of Treatment (SVR24)
Description
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.
Time Frame
24 weeks after the end of treatment (EOT) (Week 32 or Week 36)
Title
Percentage of Participants Achieving a On-treatment Virologic Response
Description
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.
Time Frame
Day 14, Day 28, End of treatment (Week 8 or Week 12)
Title
Percentage of Participants With Viral Breakthrough
Description
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.
Time Frame
Up to Week 24
Title
Percentage of Participants With Viral Relapse
Description
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.
Time Frame
Up to Week 24
Title
Change From Baseline in Hepatitis C Symptom and Impact Questionnaire 4 (HCV-SIQv4) Overall Body System Score (OBSS)
Description
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.
Time Frame
Baseline (Day 1), Week 4, Week 8, Week 12, Follow-up Week 4, Follow-up Week 12 and Follow-up Week 24
Title
Change From Baseline in Fatigue Severity Scale (FSS) Score 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 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.
Time Frame
Baseline (Day 1), Week 4, Week 8, Week 12, Follow-up Week 4, Follow-up Week 12 and Follow-up Week 24
Title
Change From Baseline in Center for Epidemiologic Studies Depression Scale (CES-D) Scores
Description
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.
Time Frame
Baseline (Day 1), Week 4, Week 8, Week 12, Follow-up Week 4, Follow-up Week 12 and Follow-up Week 24
Title
Change From Baseline in EuroQol 5 Dimension (EQ-5D) Visual Analogue Scale
Description
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.
Time Frame
Baseline (Day 1), Week 4, Week 8, Week 12, Follow-up Week 4, Follow-up Week 12 and 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
No
Eligibility 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
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
Country
United States
City
Chula Vista
State/Province
California
Country
United States
City
Los Angeles
State/Province
California
Country
United States
City
San Diego
State/Province
California
Country
United States
City
Englewood
State/Province
Colorado
Country
United States
City
Bradenton
State/Province
Florida
Country
United States
City
Jacksonville
State/Province
Florida
Country
United States
City
Lauderdale Lakes
State/Province
Florida
Country
United States
City
Maitland
State/Province
Florida
Country
United States
City
Miami
State/Province
Florida
Country
United States
City
Orlando
State/Province
Florida
Country
United States
City
Wellington
State/Province
Florida
Country
United States
City
Zephyrhills
State/Province
Florida
Country
United States
City
Atlanta
State/Province
Georgia
Country
United States
City
Columbus
State/Province
Georgia
Country
United States
City
Marietta
State/Province
Georgia
Country
United States
City
Indianapolis
State/Province
Indiana
Country
United States
City
Jackson
State/Province
Mississippi
Country
United States
City
Kansas City
State/Province
Missouri
Country
United States
City
Hillsborough
State/Province
New Jersey
Country
United States
City
Vineland
State/Province
New Jersey
Country
United States
City
Manhasset
State/Province
New York
Country
United States
City
New York
State/Province
New York
Country
United States
City
Ny
State/Province
New York
Country
United States
City
Asheville
State/Province
North Carolina
Country
United States
City
Winston Salem
State/Province
North Carolina
Country
United States
City
Pittsburgh
State/Province
Pennsylvania
Country
United States
City
East Greenwich
State/Province
Rhode Island
Country
United States
City
Providence
State/Province
Rhode Island
Country
United States
City
Greer
State/Province
South Carolina
Country
United States
City
Germantown
State/Province
Tennessee
Country
United States
City
Knoxville
State/Province
Tennessee
Country
United States
City
Nashville
State/Province
Tennessee
Country
United States
City
Arlington
State/Province
Texas
Country
United States
City
Austin
State/Province
Texas
Country
United States
City
San Antonio
State/Province
Texas
Country
United States
City
Falls Church
State/Province
Virginia
Country
United States
City
Norfolk
State/Province
Virginia
Country
United States
City
Vancouver
State/Province
British Columbia
Country
Canada
City
Montreal
State/Province
Quebec
Country
Canada

12. IPD Sharing Statement

Citations:
PubMed Identifier
26799692
Citation
Kwo P, Gitlin N, Nahass R, Bernstein D, Etzkorn K, Rojter S, Schiff E, Davis M, Ruane P, Younes Z, Kalmeijer R, Sinha R, Peeters M, Lenz O, Fevery B, De La Rosa G, Scott J, Witek J. Simeprevir plus sofosbuvir (12 and 8 weeks) in hepatitis C virus genotype 1-infected patients without cirrhosis: OPTIMIST-1, a phase 3, randomized study. Hepatology. 2016 Aug;64(2):370-80. doi: 10.1002/hep.28467. Epub 2016 Mar 22.
Results Reference
derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs