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

Purpose

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.

Condition	Intervention	Phase
Hepatitis C Virus Infection	Drug: Simeprevir Drug: Sofosbuvir	Phase 3


Study Type:	Interventional
Study Design:	Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	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

Resource links provided by NLM:

Genetics Home Reference related topics: North American Indian childhood cirrhosis

MedlinePlus related topics: Cirrhosis Hepatitis Hepatitis A Hepatitis C

Drug Information available for: Simeprevir Sofosbuvir

U.S. FDA Resources

Further study details as provided by Janssen Infectious Diseases BVBA:

Primary Outcome Measures:

Percentage of Participants With a Sustained Virologic Response (SVR) 12 Weeks After the Actual End of Treatment (EOT) [ Time Frame: Week 24 ]
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.

Secondary Outcome Measures:

Percentage of Participants With a Sustained Virologic Response (SVR) 4 Weeks After the Actual End of Treatment (EOT) [ Time Frame: Week 16 ]
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.
Percentage of Participants With a Sustained Virologic Response (SVR) 24 Weeks After the Actual End of Treatment (EOT) [ Time Frame: Week 36 ]
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.
Percentage of Participants With On-treatment Virologic Response [ Time Frame: Week 2, 4 and End of Treatment (Week 12) ]
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.
Percentage of Participants With On-treatment Failure [ Time Frame: Week 12 ]
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.
Percentage of Participants With Viral Breakthrough [ Time Frame: Up to End of Treatment (Week 12) ]
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).
Percentage of Participants With Viral Relapse [ Time Frame: During the Follow-up (Week 24) ]
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.
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 [ Time Frame: Baseline, Week 4, Week 12 and 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.
Change From Baseline in Fatigue Severity Score (FSS) up to Follow-up Week 24 [ Time Frame: Baseline, Week 12, Follow-up Week 12 and 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.
Percentage of Participants With Depression by Using Center for Epidemiologic Studies Depression Scale (CES-D) [ Time Frame: Baseline, Week 12, Follow-up Week 12 and 24 ]
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.
Change From Baseline in EuroQol 5 Dimension Questionnaire (EQ-5D) up to Follow-up Week 24 [ Time Frame: Baseline, Follow-up Week 12 and 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).
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 [ Time Frame: Baseline, Day 3, Week 1, 2, 3, 4, 8, 12, Follow-up Week 4, 12 and 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.


Enrollment:	103
Study Start Date:	April 2014
Study Completion Date:	April 2015
Primary Completion Date:	January 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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.

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.

Eligibility


Ages Eligible for Study:	18 Years to 70 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02114151

Show 34 Study Locations

Sponsors and Collaborators

Janssen Infectious Diseases BVBA

Investigators


Study Director:	Janssen Infectious Diseases BVBA Clinical Trial	Janssen Infectious Diseases BVBA

More Information


Responsible Party:	Janssen Infectious Diseases BVBA
ClinicalTrials.gov Identifier:	NCT02114151 History of Changes
Other Study ID Numbers:	CR103431 TMC435HPC3018 ( Other Identifier: Janssen Infectious Diseases BVBA )
Study First Received:	April 2, 2014
Results First Received:	January 21, 2016
Last Updated:	March 7, 2016

Keywords provided by Janssen Infectious Diseases BVBA:


Hepatitis C Virus Infection Simeprevir Sofosbuvir HCV Cirrhosis

Additional relevant MeSH terms:


Infection Communicable Diseases Hepatitis Hepatitis A Hepatitis C Fibrosis Liver Cirrhosis Virus Diseases Liver Diseases Digestive System Diseases Hepatitis, Viral, Human Enterovirus Infections	Picornaviridae Infections RNA Virus Infections Flaviviridae Infections Pathologic Processes Sofosbuvir Simeprevir Antiviral Agents Anti-Infective Agents Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 17, 2017