Clinical trial NCT01289782: An Efficacy, Safety, and Tolerability Study of TMC435 in Treatment-naive, Genotype 1 Hepatitis C-infected Patients
Official title: A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Investigate the Efficacy, Safety and Tolerability of TMC435 vs Placebo as Part of a Treatment Regimen Including Peginterferon α-2a and Ribavirin in Treatment-naïve, Genotype 1 Hepatitis Cinfected Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hepatitis C
Keywords: Hepatitis C
TMC435
HCV
Hep C
Genotype 1
Lead sponsor: Janssen R&D Ireland
Sponsor class: INDUSTRY
First posted: 2011-02-04
Enrollment: 395
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to investigate the effectiveness and safety of TMC435 compared with placebo in participants who are infected with genotype 1 hepatitis C virus who have never received treatment before. Participants will also receive peginterferon alpha-2a and ribavirin as part of their treatment.

Detailed description: This is a randomized, double-blind (neither physician nor participants know the name of the assigned drug), placebo-controlled study of TMC435 in participants who are infected with genotype 1 hepatitis C virus (HCV), who have never received treatment for HCV infection before. Participants in this study will also receive two other drugs for their HCV infection called peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV). The purpose of the study is to investigate if TMC435 is superior to placebo in reducing plasma levels of HCV ribonucleic acid (RNA) to an undetectable level 12 weeks after the end of treatment. For the first 12 weeks, participants will take either TMC435 or placebo, plus PegIFNα-2a and RBV. For the next 12 weeks, participants will take PegIFN alpha-2a and RBV only. After that, some participants will continue to take PegIFN alpha-2a and RBV for up to 24 additional weeks and some will stop taking PegIFN alpha-2a and RBV depending on response-guided treatment criteria. The study doctor will inform each participant about how to take their study medication and when they should stop taking it. After a participant stops taking study medication, they will continue to come to the doctor's office for study visits until a total of 72 weeks after they enroll in the study. The total duration of the study is 78 weeks (including screening). Participants will be monitored for safety throughout the study.

Eligibility criteria: Inclusion Criteria:

* Genotype 1 hepatitis C infection (confirmed at screening)
* Patient has not received any prior treatment for hepatitis C
* Patient must have had a liver biopsy within 3 years before screening (or between the screening and baseline visit) showing chronic hepatitis C infection
* Must agree to use 2 forms of effective contraception throughout study (both males and females)

Exclusion Criteria:

* Infection with HIV or non genotype 1 hepatitis C
* Liver disease not related to hepatitic C infection
* Hepatic decompensation
* Significant laboratory abnormalities or other active diseases
* Pregnant or planning to become pregnant

Primary outcomes:
measure: The Percentage of Participants Achieving a Sustained Virologic Response 12 Weeks After the Planned End of Treatment (SVR12)
timeFrame: Week 36 or Week 60
Secondary outcomes:
measure: The Percentage of Participants Achieving a Sustained Virologic Response at Week 72 (SVRW72)
timeFrame: Week 72
measure: The Percentage of Participants Who Achieved a Sustained Virologic Response 24 Weeks After the Planned End of Treatment (SVR24)
timeFrame: Week 48 or Week 72
measure: The Percentage of Participants Who Achieved a Sustained Virologic Response 4 Weeks After the Planned End of Treatment (SVR4)
timeFrame: Week 28 or Week 52
measure: Change From Baseline in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)
timeFrame: Day 3, Week 1, Week 4, Week 12, Week 24, and Week 48
measure: Actual Values of log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)
timeFrame: Day 3, Week 1, Week 4, Week 12, Week 24, and Week 48
measure: Percentage of Participants With On-treatment Virologic Response at All Time Points
timeFrame: Day 3, Week 1, Week 2, Week 8, Week 16, Week 20, Week 28, Week 36, and Week 42
measure: The Percentage of Participants Achieving a Rapid Virologic Response (RVR)
timeFrame: Week 4
measure: The Percentage of Participants Achieving a Early Virologic Response (EVR)
timeFrame: Week 12
measure: The Percentage of Participants Achieving a Complete Early Virologic Response (cEVR)
timeFrame: Week 12
measure: The Percentage of Participants Achieving a Extended Rapid Virologic Response (eRVR)
timeFrame: Week 4 and 12
measure: The Percentage of Participants With <1 log10 Decrease in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) From Baseline at Week 4
timeFrame: Week 4
measure: Percentage of Participants With in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels >1000 IU/mL at Week 4
timeFrame: Week 4
measure: Percentage of Participants With Null Response
timeFrame: Week 12
measure: Percentage of Participants With Partial Response
timeFrame: Week 12
measure: Percentage of Participants With Viral Breakthrough
timeFrame: Up to Week 48
measure: Percentage of Participants With Viral Relapse
timeFrame: Up to Week 72
measure: Percentage of Participants Who Completed All Study Treatment at Week 24 Because of the Treatment Duration Rule
timeFrame: Week 24
measure: Percentage of Participants With On-treatment Failure
timeFrame: Week 48
measure: Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <25 IU/mL Undetectable or Detectable
timeFrame: Up to Week 48
measure: Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <25 IU/mL Undetectable
timeFrame: Up to Week 48
measure: Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <100 IU/mL
timeFrame: Up to Week 48
measure: Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <1000 IU/mL
timeFrame: Up to Week 48
measure: The Percentage of Participants With Viral Breakthrough at Different Time Points
timeFrame: Up to Week 48
measure: Time From End-of-treatment to Viral Relapse
timeFrame: Up to Week 72
measure: The Percentage of Participants With Normalization of Alanine Aminotransferase (ALT)
timeFrame: Up to Week 48
measure: Median Time to Normalization of Alanine Aminotransferase (ALT) Levels
timeFrame: Up to Week 48
measure: Plasma Concentration of TMC435: Area Under the Plasma Concentration-time Curve From the Time of Administration to 24 Hours After Dosing (AUC24h)
timeFrame: Fom the time of administration up to 24 hours after dosing at Weeks 2, 4, 8, and 12
measure: Plasma Concentration of TMC435: Predose Plasma Concentration (C0h)
timeFrame: Before administration of TMC435 at Weeks 2, 4, 8, and 12
measure: Plasma Concentration of TMC435: Systemic Clearance (CL)
timeFrame: Across Weeks 2, 4, 8, and 12
measure: Area Under the Curve From Baseline to Week 60 (AUC60) and Week 72 (AUC72) for the Fatigue Severity Scale (FSS) Total Scores
timeFrame: Baseline to Week 60 and Week 72
measure: Area Under the Curve From Baseline to Week 60 (AUC60) and Week 72 (AUC72) for Impairment in Overall Work Productivity Scores Due to Hepatitis C Virus (HCV) Infection and Its Treatment
timeFrame: Baseline to Week 60 and Week 72
measure: Area Under the Curve From Baseline to Week 60 (AUC60) and Week 72 (AUC72) for Impairment in Daily Activity Scores Due to Hepatitis C Virus (HCV) Infection and Its Treatment
timeFrame: Baseline to Week 60 and Week 72
measure: Area Under the Curve From Baseline to Week 60 (AUC60) and Week 72 (AUC72) in Work Productivity and Activity (WPAI) Absenteeism Scores Due to Hepatitis C Virus (HCV) Infection and Its Treatment
timeFrame: Baseline to Week 60 and Week 72
Other outcomes:
Locations:
city: Dothan
country: United States
state: Alabama
city: Hoover
country: United States
state: Alabama
city: Phoenix
country: United States
state: Arizona
city: Bakersfield
country: United States
state: California
city: Coronado
country: United States
state: California
city: Long Beach
country: United States
state: California
city: San Diego
country: United States
state: California
city: Aurora
country: United States
state: Colorado
city: Englewood
country: United States
state: Colorado
city: Miami
country: United States
state: Florida
city: Chicago
country: United States
state: Illinois
city: Jackson
country: United States
state: Mississippi
city: Tupelo
country: United States
state: Mississippi
city: Saint Louis
country: United States
state: Missouri
city: New York
country: United States
state: New York
city: Chapel Hill
country: United States
state: North Carolina
city: Cincinnati
country: United States
state: Ohio
city: Philadelphia
country: United States
state: Pennsylvania
city: Nashville
country: United States
state: Tennessee
city: Dallas
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Darlinghurst
country: Australia
city: Fitzroy
country: Australia
city: Kingswood
country: Australia
city: Melbourne
country: Australia
city: Sydney
country: Australia
city: Wolloongabba
country: Australia
city: Calgary
country: Canada
state: Alberta
city: Ottawa
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Berlin
country: Germany
city: Heidelberg
country: Germany
city: Kiel
country: Germany
city: Tübingen
country: Germany
city: Guadalajara
country: Mexico
city: Mex Ctity
country: Mexico
city: Monterrey
country: Mexico
city: Auckland
country: New Zealand
city: Christchurch
country: New Zealand
city: Hamilton
country: New Zealand
city: San Juan
country: Puerto Rico
city: Bucuresti
country: Romania
city: Moscow
country: Russian Federation
city: Nizhny Novgorod
country: Russian Federation
city: Saint-Petersburg
country: Russian Federation
city: Samara
country: Russian Federation
city: Smolensk
country: Russian Federation
city: St Petersburg
country: Russian Federation
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Sevilla N/A
country: Spain
city: Valencia
country: Spain
city: Donetsk
country: Ukraine
city: Kiev
country: Ukraine
city: Kyiv
country: Ukraine
city: Vinnytsia
country: Ukraine
city: Derby
country: United Kingdom
city: Liverpool
country: United Kingdom
city: London
country: United Kingdom
city: Nottingham
country: United Kingdom
city: Plymouth
country: United Kingdom
Study officials:
affiliation: Janssen R&D Ireland
name: Janssen R&D Ireland Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Lenz O, Verbinnen T, Fevery B, Tambuyzer L, Vijgen L, Peeters M, Buelens A, Ceulemans H, Beumont M, Picchio G, De Meyer S. Virology analyses of HCV isolates from genotype 1-infected patients treated with simeprevir plus peginterferon/ribavirin in Phase IIb/III studies. J Hepatol. 2015 May;62(5):1008-14. doi: 10.1016/j.jhep.2014.11.032. Epub 2014 Nov 28.
citation: Jacobson IM, Dore GJ, Foster GR, Fried MW, Radu M, Rafalsky VV, Moroz L, Craxi A, Peeters M, Lenz O, Ouwerkerk-Mahadevan S, De La Rosa G, Kalmeijer R, Scott J, Sinha R, Beumont-Mauviel M. Simeprevir with pegylated interferon alfa 2a plus ribavirin in treatment-naive patients with chronic hepatitis C virus genotype 1 infection (QUEST-1): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet. 2014 Aug 2;384(9941):403-13. doi: 10.1016/S0140-6736(14)60494-3. Epub 2014 Jun 4.