Clinical trial NCT02114177: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hepatitis C Virus Infection
Keywords: Hepatitis C Virus Infection
Simeprevir
Sofosbuvir
HCV
Cirrhosis
Lead sponsor: Janssen Infectious Diseases BVBA
Sponsor class: INDUSTRY
First posted: 2014-04-15
Enrollment: 310
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Percentage of Participants Achieving a Sustained Virologic Response 12 Weeks After the Actual End of Treatment (SVR12)
timeFrame: 12 weeks after the end of treatment (EOT) (Week 20 or Week 24)
Secondary outcomes:
measure: Percentage of Participants Achieving a Sustained Virologic Response 4 Weeks After the Actual End of Treatment (SVR4)
timeFrame: 4 weeks after the end of treatment (EOT) (Week 12 or Week 16)
measure: Percentage of Participants Achieving a Sustained Virologic Response 24 Weeks After the Actual End of Treatment (SVR24)
timeFrame: 24 weeks after the end of treatment (EOT) (Week 32 or Week 36)
measure: Percentage of Participants Achieving a On-treatment Virologic Response
timeFrame: Day 14, Day 28, End of treatment (Week 8 or Week 12)
measure: Percentage of Participants With Viral Breakthrough
timeFrame: Up to Week 24
measure: Percentage of Participants With Viral Relapse
timeFrame: Up to Week 24
measure: Change From Baseline in Hepatitis C Symptom and Impact Questionnaire 4 (HCV-SIQv4) Overall Body System Score (OBSS)
timeFrame: Baseline (Day 1), Week 4, Week 8, Week 12, Follow-up Week 4, Follow-up Week 12 and Follow-up Week 24
measure: Change From Baseline in Fatigue Severity Scale (FSS) Score up to Follow-up Week 24
timeFrame: Baseline (Day 1), Week 4, Week 8, Week 12, Follow-up Week 4, Follow-up Week 12 and Follow-up Week 24
measure: Change From Baseline in Center for Epidemiologic Studies Depression Scale (CES-D) Scores
timeFrame: Baseline (Day 1), Week 4, Week 8, Week 12, Follow-up Week 4, Follow-up Week 12 and Follow-up Week 24
measure: Change From Baseline in EuroQol 5 Dimension (EQ-5D) Visual Analogue Scale
timeFrame: Baseline (Day 1), Week 4, Week 8, Week 12, Follow-up Week 4, Follow-up Week 12 and Follow-up Week 24
Other outcomes:
Locations:
city: Dothan
country: United States
state: Alabama
city: Bakersfield
country: United States
state: California
city: Chula Vista
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: San Diego
country: United States
state: California
city: Englewood
country: United States
state: Colorado
city: Bradenton
country: United States
state: Florida
city: Jacksonville
country: United States
state: Florida
city: Lauderdale Lakes
country: United States
state: Florida
city: Maitland
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: Wellington
country: United States
state: Florida
city: Zephyrhills
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Columbus
country: United States
state: Georgia
city: Marietta
country: United States
state: Georgia
city: Indianapolis
country: United States
state: Indiana
city: Jackson
country: United States
state: Mississippi
city: Kansas City
country: United States
state: Missouri
city: Hillsborough
country: United States
state: New Jersey
city: Vineland
country: United States
state: New Jersey
city: Manhasset
country: United States
state: New York
city: New York
country: United States
state: New York
city: Ny
country: United States
state: New York
city: Asheville
country: United States
state: North Carolina
city: Winston Salem
country: United States
state: North Carolina
city: Pittsburgh
country: United States
state: Pennsylvania
city: East Greenwich
country: United States
state: Rhode Island
city: Providence
country: United States
state: Rhode Island
city: Greer
country: United States
state: South Carolina
city: Germantown
country: United States
state: Tennessee
city: Knoxville
country: United States
state: Tennessee
city: Nashville
country: United States
state: Tennessee
city: Arlington
country: United States
state: Texas
city: Austin
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Falls Church
country: United States
state: Virginia
city: Norfolk
country: United States
state: Virginia
city: Vancouver
country: Canada
state: British Columbia
city: Montreal
country: Canada
state: Quebec
Study officials:
affiliation: Janssen Infectious Diseases BVBA
name: Janssen Infectious Diseases BVBA Clinical Trial
role: STUDY_DIRECTOR
References:
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.