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

Hepatitis C Virus Infection Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02114151
• Other study ID #: CR103431
• Secondary ID: TMC435HPC3018
• Status: Completed
• Phase: Phase 3
• First received: April 2, 2014
• Last updated: June 4, 2015
• Start date: April 2014
• Est. completion date: April 2015

Study information

• Verified date: June 2015
• Source: Janssen Infectious Diseases BVBA
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 103
• Est. completion date: April 2015
• Est. primary completion date: January 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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 Design

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

Related Conditions & MeSH terms

• Communicable Diseases
• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C Virus Infection
• Infection
• Virus Diseases

Intervention

Drug:
• Simeprevir
100 participants will receive 1 capsule of 150 mg orally once daily for 12 weeks.
• Sofosbuvir
100 participants will receive 1 tablet of 400 mg sofosbuvir orally once daily for 12 weeks.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Infectious Diseases BVBA

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants Achieving a Sustained Virologic Response 12 Weeks After the Planned end of Treatment (SVR12)	SVR12 defined as the number of participants with less than 25 IU/mL detectable or undetectable plasma Hepatitis C virus ribonucleic acid 12 weeks after planned end of treatment.The end of treatment is at Week 12; therefore, the outcome will be measured at Week 24.	Week 24	No
Secondary	Number of Participants Achieving a Sustained Virologic Response 4 Weeks After the Planned end of Treatment (SVR4)	SVR4 is defined as the number of participants with less than 25 IU/mL detectable or undetectable plasma Hepatitis C virus (HCV) ribonucleic acid (RNA) 4 weeks after planned end of treatment.The end of treatment is at Week 12; therefore, the outcome will be measured at Week 16.	Week 16	No
Secondary	Number of Participants Achieving a Sustained Virologic Response 24 Weeks After the Planned end of Treatment (SVR24)	SVR24 is defined as the number of participants with less than 25 IU/mL detectable or undetectable plasma HCV RNA 24 weeks after planned end of treatment. The end of treatment is at Week 12; therefore, the outcome will be measured at Week 36.	Week 36	No
Secondary	Number of Participants Achieving a On-treatment Virologic Response	On-treatment virologic response is defined as the change from baseline in log10 hepatitis C virus ribonucleic acid.	Day 1, Day 3, Day 7, Week 2, Week 3, Week 4, Week 8, Week 12, Week 16, Week 24, Week 36	No
Secondary	Number of Participants with Viral Breakthrough	Viral breakthrough is defined as the number of participants with greater than 1 log10 IU/mL increase in plasma HCV RNA level from the lowest level reached (ie, lowest value measured in between baseline and current value), or a confirmed plasma HCV RNA level of greater than 100 IU/mL in participants whose plasma HCV RNA had previously been less than 25 IU/mL.	Up to Week 40	No
Secondary	Number of Participants with Viral Relapse	Viral relapse is defined as the number of participants who did not achieve sustained virologic response, have less than 25 IU/mL undetectable plasma HCV RNA at end of treatment, and greater than or equal to 25 IU/mL plasma HCV RNA during the follow-up phase.	Up to Week 40	No
Secondary	Change from baseline in Hepatitis C Symptom and Impact Questionnaire (HCV-SIQ) scores	HCV-SIQv4 is a self-administered questionnaire which contains 33 items classified as 3 categories of scores: sum of responses to 29 symptom items as a symptom severity score category, sum of response to 3 items as a time missed from work/school category, and 1 response to question regarding the impact of symptoms on daily activities as an impairment in daily activity score category. The total score is the sum of scores of these 3 categories. Higher HCV-SIQv4 scores indicate worse symptom severity, more time missed from work/school, and more impairment in daily activities.	Baseline (Day 1) to Week 36	No
Secondary	Change From Baseline in Fatigue Severity Scale (FSS) Scores	The FSS is a self-administered questionnaire with 9 items developed to assess disabling fatigue. These 9 item responses are measured on a 7-point Likert scale ranging from strongly disagree (1 point) to strongly agree (7 points). The 9 items are averaged to produce a total score. A lower total score indicates less effect of fatigue on everyday life.	Baseline (Day 1) to Week 36	No
Secondary	Change From Baseline in Center for Epidemiologic Studies Depression Scale (CES-D) Scores	The CES-D scale assesses how often during the past week participants experienced 20 symptoms commonly associated with major depression. CES-D scores range from 0 (no symptoms) to 60 (all 20 symptoms most or all of the time during the past 5-7 days). The CES-D scores between 16 and 23 points indicate mild to moderate depressive illness while CES-D scores greater than or equal to 23 indicate probable major depressive illness.	Baseline (Day 1) to Week 36	No
Secondary	Change From Baseline in EuroQol 5 Dimension (EQ-5D) Questionnaire Scores	The EQ-5D questionnaire is a brief, generic health-related quality of life assessment (HRQOL) that can also be used to incorporate participant preferences into health economic evaluations. The EQ-5D questionnaire assesses 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). Lower scores indicate worsening. EQ-5D scores include EQ-5D valuation index score which includes a weighted scoring of the 5 dimension scores with a possible range from 0 to 1, EQ-5D visual analog scale (VAS) is a 20 cm vertical VAS with scores ranging from 0 (worst imaginable health) to 100 (perfect health), and EQ5D descriptive system scores consist of five scores reflecting each of the 5 EQ-5D health dimensions ranging from 0 [no limitation] to 4 [incapacity]).	Baseline (Day 1) to Week 36	No