Clinical trial NCT02268864: A Study to Assess the Efficacy and Safety of the Combination of Simeprevir and Daclatasvir in Chronic Hepatitis C Genotype 1b-Infected Participants
Official title: A Phase 2, Open-label Study to Investigate the Efficacy and Safety of the Combination of Simeprevir and Daclatasvir in Chronic Hepatitis C Genotype 1b-Infected Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatitis C, Chronic
Keywords: Hepatitis C Chronic
Simeprevir
Daclatasvir
Lead sponsor: Janssen-Cilag International NV
Sponsor class: INDUSTRY
First posted: 2014-10-20
Enrollment: 106
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the efficacy of a 12- or 24-week treatment regimen of simeprevir in combination with daclatasvir, as measured by sustain virologic response 12 (SVR12), in treatment-naive, chronic hepatitis C virus (HCV) genotype 1b-infected participants who have advanced fibrosis or compensated cirrhosis (METAVIR F3/F4).

Detailed description: This is an open-label (all people know which treatment the participants receive) study to investigate the efficacy, safety and tolerability of simeprevir and daclatasvir in chronic Hepatitis (inflammation of the liver) C virus (HCV) genotype 1b infected participants who are treatment-naive. The total study duration for each participant will be approximately 40 weeks or approximately 52 weeks. The study will consist of 4 parts: Screening Phase (approximately 4 weeks) and open-label treatment Phase (12 weeks), optional open label treatment phase extension (12 Weeks) and follow-up Phase (up to Week 40 or Week 52). Participants will receive simeprevir (150 milligram \[mg\] capsule) and daclatasvir (60 mg tablet) orally once daily for 12 or 24 weeks. Efficacy will be primarily evaluated by percentage of participants with SVR12. Participants' safety will be monitored throughout the study.

Eligibility criteria: Inclusion Criteria:

* Participant must have chronic Hepatitis C virus (HCV) genotype 1b infection confirmed at Screening
* Participant must have HCV ribonucleic acid (RNA) greater than (\>) 10,000 international unit per milliliter (IU/mL) at Screening
* Participant must have documented fibrosis stage at Screening (or between Screening and Day 1 \[baseline\]). Liver disease will be staged based on one of the following methods. a) Shear wave elastography (Fibroscan) within less than or equal to (\<=) 6 months before Screening or between Screening and Day 1 (baseline). METAVIR F3 \> 9.6 Kilopascals (kPa) and the cut-off for cirrhosis is greater than or equal to (\>=) 14.6 kPa. b) A biopsy documenting METAVIR F3-F4. Biopsy performed within the 24 months before Screening will be accepted for participants with METAVIR score F3. For cirrhotic participants (METAVIR score F4) a biopsy performed at any previous time is acceptable
* Participants who have cirrhosis must have an hepatic imaging procedure (ultrasound, computed tomography \[CT\] scan or magnetic resonance imaging \[MRI\]) within 6 months prior to the Screening visit (or between Screening and Day 1) with no findings suspicious for hepatocellular carcinoma
* Participant must have a body mass index (BMI) \>= 18 Kilogram per meter\^2 (kg/m\^2)
* Participant must be treatment naive (that is, have not received prior treatment for HCV with any approved or investigational drug)

Exclusion Criteria:

* Participant has co-infection with HCV of another genotype; a) Participant who has HCV genotype 1b has coinfection with HCV of a genotype other than genotype 1b
* Chronic HCV genotype 1b-infected participant who has the presence of genetic variants coding for the NS5A-Y93H and/or L31M/V amino acid substitutions at Screening
* Participant has evidence of current or previous episodes of hepatic decompensation (including controlled or uncontrolled ascites, bleeding varices or hepatic encephalopathy)
* Participant has chronic liver disease of a non-HCV etiology (including but not limited to hemochromatosis, Wilson's disease, alfa 1-antitrypsin deficiency, cholangitis, drug- or alcohol-related liver disease, primary biliary cirrhosis)
* Participant has any other uncontrolled clinically significant disease or clinically significant findings during Screening that in the opinion of the investigator could compromise the participants' safety or could interfere with the participant participating in and completing the study
* Participant has coinfection with hepatitis A or hepatitis B virus (hepatitis A antibody immunoglobulin M \[IgM\] or hepatitis B surface antigen \[HBsAg\] positive at Screening)
* Participant has received a solid organ transplant

Primary outcomes:
measure: Percentage of Participants With Sustained Virologic Response 12 Weeks After End of Study Drug Treatment (SVR12)
timeFrame: At 12 weeks after end of treatment
Secondary outcomes:
measure: Percentage of Participants With Sustained Virologic Response 4 Weeks After End of Study Drug Treatment (SVR4)
timeFrame: At 4 weeks after actual EOT
measure: Percentage of Participants With SVR 24 Weeks After End of Study Drug Treatment (SVR 24)
timeFrame: At 24 weeks after actual EOT
measure: Percentage of Participants With On-treatment Failure
timeFrame: Up to Week 24 after actual EOT
measure: Number of Participants With Viral Breakthrough
timeFrame: Up to Week 24
measure: Number of Participants With Viral Relapse
timeFrame: Up to Week 24 after actual EOT
Other outcomes:
Locations:
city: Antwerpen
country: Belgium
city: Brussel
country: Belgium
city: Gent
country: Belgium
city: Creteil
country: France
city: Lyon
country: France
city: Montpellier
country: France
city: Nice N/A
country: France
city: Paris Cedex 12
country: France
city: Paris
country: France
city: Vandoeuvre Les Nancy
country: France
city: Frankfurt
country: Germany
city: Hamburg
country: Germany
city: Hannover
country: Germany
city: Kiel
country: Germany
city: Tübingen
country: Germany
city: Würzburg
country: Germany
city: Budapest
country: Hungary
city: Debrecen
country: Hungary
city: Badalona
country: Spain
city: Barcelona
country: Spain
city: Santander
country: Spain
city: Valencia
country: Spain
city: Birmingham
country: United Kingdom
city: London
country: United Kingdom
Study officials:
affiliation: Janssen-Cilag International NV
name: Janssen-Cilag International NV Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Hezode C, Almasio PL, Bourgeois S, Buggisch P, Brown A, Diago M, Horsmans Y, Serfaty L, Szalay F, Gaeta GB, Planas R, Schlag M, Lonjon-Domanec I, Omoruyi E, DeMasi R, Zeuzem S. Simeprevir and daclatasvir for 12 or 24 weeks in treatment-naive patients with hepatitis C virus genotype 1b and advanced liver disease. Liver Int. 2017 Sep;37(9):1304-1313. doi: 10.1111/liv.13376. Epub 2017 Mar 13.