A Study to Assess the Efficacy and Safety of the Combination of Simeprevir and Daclatasvir in Chronic Hepatitis C Genotype 1b-Infected Participants

Hepatitis C, Chronic Clinical Trial

— COMMIT  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02268864
• Other study ID #: CR105490
• Secondary ID: 2014-003413-28TM
• Status: Completed
• Phase: Phase 2
• First received: October 15, 2014
• Last updated: May 26, 2016
• Start date: January 2015
• Est. completion date: April 2016

Study information

• Verified date: May 2016
• Source: Janssen-Cilag International NV
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicinal Products and Health ProductsFrance: The French National Agency for Medicines and Health Products SafetyGermany: Federal Institute for Drugs and Medical DevicesHungary: Ministry of Health, Social and Family AffairsSpain: Ministry of HealthUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyBelgium: The Federal Public Service (FPS) Health, Food Chain Safety and EnvironmentGermany: Ethics CommissionGreat Britain: Medicines and Healthcare Products Regulatory AgencyGreat Britain: Research Ethics Committee
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 106
• Est. completion date: April 2016
• Est. primary completion date: January 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• Simeprevir
Simeprevir 150 mg oral capsule will be administered once daily for 12 or 24 weeks.
• Daclatasvir
Daclatasvir 60 mg oral tablet will be administered once daily for 12 or 24 weeks.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Janssen-Cilag International NV

Countries where clinical trial is conducted

Belgium,  France,  Germany,  Hungary,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Sustained Virologic Response 12 Weeks After end of Study Drug Treatment (SVR12)	Participants who are infected with hepatitis C virus (HCV) genotype 1b and have advanced fibrosis or compensated cirrhosis (METAVIR F3/F4) are assessed. Participants will be considered to have achieved SVR12 if the HCV ribonucleic acid (RNA) is less than (<) lower limit of quantification (LLOQ; 15 international unit per milliliter [IU/mL]) detectable or undetectable at 12 weeks after the end of study drug treatment.	12 weeks after end of treatment (Week 24 or Week 36)	No
Secondary	Percentage of Participants with SVR 4 Weeks After end of Study Drug Treatment (SVR4) and SVR 24 Weeks After end of Study Drug Treatment (SVR24)	Participants will be considered to have achieved SVR4 and SVR24 if the HCV RNA is	For SVR4: Week 16 or 28; for SVR24: Week 36 or 48	No
Secondary	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.	Week 12 or Week 24	No
Secondary	Percentage of Participants with viral breakthrough	Viral breakthrough is defined as confirmed >1.0 log10 increase in HCV RNA from nadir or confirmed HCV RNA >100 international unit per milliliter (IU/mL) in participants who had previously achieved HCV RNA	Up to Week 12 or Week 24	No
Secondary	Percentage of Participants With Viral Relapse	Viral relapse is defined as participants who do not achieve SVR12, with undetectable HCV RNA at the actual end of study drug treatment and confirmed HCV RNA greater than or equal to (>=) LLOQ (15 IU/mL) at Week 16, 24 and 36.	Week 4, 12 and 24 post treatment	No