Clinical trial NCT01846832: A Study of TMC435 Plus Pegylated Interferon Alfa-2a and Ribavirin in Participants With Chronic HCV Infection
Official title: A Phase 3, Open-Label, Single-Arm Study to Evaluate the Safety and Efficacy of TMC435 Plus Pegylated Interferon Alfa-2a and Ribavirin Administered for 12 Weeks in Treatment-Naïve Subjects With Chronic Genotype 1 or Genotype 4 HCV Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hepatitis C, Chronic
Infection
Keywords: Hepatitis C, Chronic
Infection
Triple therapy
TMC435
simeprevir
Pegylated interferon alfa-2a (PegIFNα-2a)
ribavirin (RBV)
PEGASYS
COPEGUS
Lead sponsor: Janssen-Cilag International NV
Sponsor class: INDUSTRY
First posted: 2013-05-03
Enrollment: 232
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
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 evaluate the efficacy, tolerability, and safety of 12-weeks of treatment with TMC435 plus pegylated interferon alfa-2a (PegIFNα-2a) and ribavirin (RBV) in previously untreated adult participants with genotype 1 or genotype 4 chronic Hepatitis C Virus (HCV) infection.

Detailed description: This is a multicenter, international study where all participants will receive triple therapy with the following 3 medications: TMC435 also referred to as simeprevir (formerly known as TMC435350) which is an investigational medication in development for the treatment of chronic hepatitis C virus (HCV) infection, pegylated interferon alfa-2a (PegIFNα-2a), and ribavirin (RBV). PegIFNα-2a and RBV are commercially available therapies for HCV infection. Participants will receive treatment with TMC435, PegIFNα-2a, and RBV for 12 weeks. If blood levels of HCV ribonucleic acid (RNA) monitored at Weeks 2, 4, and 8 are below 25 IU/mL, all treatment will be stopped at Week 12. If HCV RNA values are above 25 IU/mL at Weeks 2, 4, or 8, treatment with PegIFNα-2a and RBV will continue for an additional 12 weeks (up to Week 24) unless protocol-specified stopping criteria are met at Week 4 or 12, at which time all treatment will be discontinued. The study will be conducted in 3 phases: a screening phase of maximum 6 weeks, a treatment phase extending from Day 1 (baseline) up to 12 or 24 weeks depending on the response to treatment, and a posttreatment follow-up period of 24 weeks after the participant's last planned dose of study drug. The duration of the participation (excluding screening phase) for each participant will vary between 36 and 48 weeks, depending on the response to treatment. Blood samples for laboratory analysis will be obtained from participants at protocol-specified time points during the study and participant safety will be monitored throughout the study.

Eligibility criteria: Inclusion Criteria:

* treatment-naïve with confirmed chronic Hepatitis C Virus (HCV) infection
* liver biopsy performed within 2 years prior to screening or non-invasive confirmation of the liver disease stage (by transient elastography) performed within 6 months prior to screening
* liver disease stage equivalent to Metavir Score F0-F2 (no fibrosis, or portal fibrosis without or with few septa)

Exclusion Criteria:

-Participants with advanced liver disease equivalent to Metavir score F3-F4 (bridging fibrosis or cirrhosis), with hepatic decompensation, with any liver disease of non-HCV etiology, and/or with a non-genotype 1 or non-genotype 4 hepatitis C, hepatitis B or HIV co-infection will be excluded from the study

Primary outcomes:
measure: The proportion (percentage) of participants infected wtih genotype 1 HCV with a sustained virologic response 12 weeks after planned end of treatment (SVR12)
timeFrame: Week 24
Secondary outcomes:
measure: The proportion (percentage) of participants infected wtih genotype 4 HCV with a sustained virologic response 12 weeks after planned end of treatment (SVR12)
timeFrame: Week 24
measure: The proportion (percentage) of participants who achieve rapid virologic response (RVR)
timeFrame: Week 4
measure: The proportion (percentage) of participants who achieve virologic response at Week 2 (W2VR)
timeFrame: Week 2
measure: The proportion (percentage) of participants with sustained virologic response 24 weeks after planned end of treatment (SVR24)
timeFrame: Week 48
measure: The proportion (percentage) of participants with sustained virologic response 12 weeks after planned end of treatment (SVR12)
timeFrame: Week 24
measure: The proportion (percentage) of participants with > or = 2 log decrease in hepatitis C virus (HCV) RNA at each time point
timeFrame: Up to Week 48
measure: The proportion (percentage) of participants with hepatitis C virus (HCV) RNA < 25 IU/mL undetectable at each time point
timeFrame: Up to Week 48
measure: The proportion (percentage) of participants with viral breakthrough
timeFrame: Up to Week 48
measure: The proportion (percentage) of participants with viral relapse
timeFrame: Up to Week 48
measure: Change from Baseline in the Hepatitis C Treatment Symptom & Impact Questionnaire (HCV SIQ) symptom and impact scores
timeFrame: Day 1 and at each study visit up to Week 48
measure: Change from Baseline in The Fatigue Severity Scale (FSS) total score
timeFrame: Day 1 and at each study visit up to Week 48
measure: Change from Baseline in The Center for Epidemiologic Studies Depression Scale (CES-D) score
timeFrame: Day 1 and at each study visit up to Week 48
measure: Change from Baseline in The Work Productivity and Activity Index (WPAI) for Hepatitis C missed work time, daily activity impairment, and productivity scores
timeFrame: Day 1 and at each study visit up to Week 48
measure: Change from Baseline in The EuroQol 5 Dimension (EQ5D) Visual Analog Scale (VAS) valuation index, and Descriptive System scores
timeFrame: Day 1 and at each study visit up to Week 48
measure: The proportion (percentage) of participants with normalized alanine aminotransferase (ALT) levels
timeFrame: Up to Week 48
measure: Change from Screening in liver disease stage assessment
timeFrame: Week -6; Week 48
measure: The number of participants reporting adverse events as a measure of safety and tolerability
timeFrame: Up to Week 48
Other outcomes:
Locations:
city: Linz
country: Austria
city: Wien
country: Austria
city: Brussels
country: Belgium
city: Brussel
country: Belgium
city: Edegem
country: Belgium
city: Clichy
country: France
city: Limoges Cedex
country: France
city: Orleans
country: France
city: St Laurent Du Var
country: France
city: Berlin
country: Germany
city: Düsseldorf
country: Germany
city: Frankfurt
country: Germany
city: Hamburg
country: Germany
city: Würzburg
country: Germany
city: Riyadh
country: Saudi Arabia
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Valencia
country: Spain
city: Valme
country: Spain
city: Glasgow
country: United Kingdom
city: London
country: United Kingdom
Study officials:
affiliation: Janssen-Cilag International NV
name: JJanssen-Cilag International NV Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Asselah T, Moreno C, Sarrazin C, Gschwantler M, Foster GR, Craxi A, Buggisch P, Ryan R, Lenz O, Scott J, Van Dooren G, Lonjon-Domanec I, Schlag M, Buti M. An Open-Label Trial of 12-Week Simeprevir plus Peginterferon/Ribavirin (PR) in Treatment-Naive Patients with Hepatitis C Virus (HCV) Genotype 1 (GT1). PLoS One. 2016 Jul 18;11(7):e0158526. doi: 10.1371/journal.pone.0158526. eCollection 2016.