Efficacy and Safety Study of Simeprevir in Combination With Sofosbuvir in Participants With Genotype 1 Chronic Hepatitis C Virus Infection and Cirrhosis

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

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.

Study Overview

• Status: Completed
• Conditions: Hepatitis C Virus Infection
• Intervention / Treatment: Drug: Simeprevir; Drug: Sofosbuvir

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.

• Study Type: Interventional
• Enrollment (Actual): 103
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada
  • Quebec
    • Montreal, Quebec, Canada
• United States
  • Alabama
    • Dothan, Alabama, United States
  • California
    • Bakersfield, California, United States
    • Chula Vista, California, United States
    • Los Angeles, California, United States
    • San Diego, California, United States
  • Colorado
    • Englewood, Colorado, United States
  • Florida
    • Bradenton, Florida, United States
    • Lauderdale Lakes, Florida, United States
    • Maitland, Florida, United States
    • Miami, Florida, United States
    • Orlando, Florida, United States
    • Wellington, Florida, United States
  • Georgia
    • Atlanta, Georgia, United States
    • Columbus, Georgia, United States
    • Marietta, Georgia, United States
  • Mississippi
    • Jackson, Mississippi, United States
  • Missouri
    • Kansas City, Missouri, United States
  • New Jersey
    • Hillsborough, New Jersey, United States
    • Vineland, New Jersey, United States
  • New York
    • New York, New York, United States
  • North Carolina
    • Asheville, North Carolina, United States
    • Winston Salem, North Carolina, United States
  • Rhode Island
    • East Greenwich, Rhode Island, United States
    • Providence, Rhode Island, United States
  • South Carolina
    • Greer, South Carolina, United States
  • Tennessee
    • Germantown, Tennessee, United States
    • Knoxville, Tennessee, United States
    • Nashville, Tennessee, United States
  • Texas
    • Arlington, Texas, United States
    • Austin, Texas, United States
    • San Antonio, Texas, United States
  • Virginia
    • Norfolk, Virginia, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1 (Simeprevir/Sofosbuvir); 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.	Drug: Simeprevir; 100 participants will receive 1 capsule of 150 mg orally once daily for 12 weeks.; Drug: Sofosbuvir; 100 participants will receive 1 tablet of 400 mg sofosbuvir orally once daily for 12 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Week 16
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.	Week 36
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.	Week 2, 4 and End of Treatment (Week 12)
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
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).	Up to End of Treatment (Week 12)
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.	During the Follow-up (Week 24)
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.	Baseline, Week 4, Week 12 and Follow-Up Week 12
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.	Baseline, Week 12, Follow-up Week 12 and 24
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.	Baseline, Week 12, Follow-up Week 12 and 24
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).	Baseline, Follow-up Week 12 and 24
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.	Baseline, Day 3, Week 1, 2, 3, 4, 8, 12, Follow-up Week 4, 12 and 24

Collaborators and Investigators

• Sponsor: Janssen Infectious Diseases BVBA

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (Actual): January 1, 2015
• Study Completion (Actual): April 1, 2015

Study Registration Dates

• First Submitted: April 2, 2014
• First Submitted That Met QC Criteria: April 11, 2014
• First Posted (Estimate): April 15, 2014

Study Record Updates

• Last Update Posted (Estimate): April 4, 2016
• Last Update Submitted That Met QC Criteria: March 7, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: HCV; Simeprevir; Cirrhosis; Sofosbuvir; Hepatitis C Virus Infection
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; RNA Virus Infections; Blood-Borne Infections; Disease Attributes; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Fibrosis; Infections; Communicable Diseases; Hepatitis; Hepatitis A; Hepatitis C; Virus Diseases; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Protease Inhibitors; Sofosbuvir; Simeprevir
• Other Study ID Numbers: CR103431; TMC435HPC3018 (Other Identifier: Janssen Infectious Diseases BVBA)