Clinical trial NCT01290679: An Efficacy, Safety, and Tolerability Study of TMC435 in Treatment-naive, Genotype 1 Hepatitis C-infected Participants
Official title: A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Investigate the Efficacy, Safety and Tolerability of TMC435 Versus Placebo as Part of a Treatment Regimen Including Peginterferon α-2a (Pegasys®) and Ribavirin (Copegus®) or Peginterferon α-2b (PegIntron®) and Ribavirin (Rebetol®) in Treatment-naïve, Genotype 1, Hepatitis C-infected 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: 2011-02-07
Enrollment: 393
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 alfa-2a or peginterferon alfa-2b and ribavirin as part of their treatment.

Detailed description: This is a randomized, double-blind (neither physician or participant knows the name of the assigned drug), placebo-controlled study of TMC435 in participants who are infected with genotype 1 hepatitis C virus who have never received treatment for this before. Participants in this study will also receive two other drugs for their infection (either peginterferon alfa-2a (Pegasys®) and ribavirin (Copegus®) or peginterferon alfa-2b (PegIntron®) and ribavirin (Rebetol®). The purpose of the study is to investigate if TMC435 is superior to placebo in reducing hepatitis C virus to an undetectable level 24 weeks after the end of treatment. For the first 12 weeks, participants will take TMC435 or placebo, plus peginterferon and ribavirin. For the next 12 weeks, participants will take peginterferon and ribavirin only. After that, some participants will continue to take peginterferon and ribavirin for up to 24 additional weeks. Other participants will stop taking peginterferon and ribavirin. 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. Study assessments at each study visit may include but are not limited to: blood and urine collection for testing, electrocardiogram (ECG) assessments (a measurement of the electrical activity of your heart), participant questionnaires, and physical examinations. TMC435 will be taken as an oral capsule of 150 mg once per day. Peginterferon (Pegasys ®) will be given as an injection of 180 µg once each week. Peginterferon (PegIntron®) will be given as an injection once each week and the dose will depend on your body weight. Ribavirin will be taken as a tablet (Copegus ®) or a capsule (Rebetol ®) twice each day and the dose will depend on your body weight.

Eligibility criteria: Inclusion Criteria:

* Genotype 1 hepatitis C infection (confirmed at screening)
* Participant has not received any prior treatment for hepatitis C
* Participant 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: Weeks 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: At protocol-specified time points from 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: Blood samples tested were taken before administration of TMC435 and at 2 random time points after dosing (taken atleast 2 hours apart from each other) at Week 2, 4, 8, and 12
measure: Plasma Concentration of TMC435: Systemic Clearance (CL)
timeFrame: At protocol-specified time points at 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 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 Activities 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 Time Missed From Work Due to Hepatitis C Virus (HCV) Infection and Its Treatment
timeFrame: Baseline to Week 60 and Week 72
Other outcomes:
Locations:
city: Los Angeles
country: United States
state: California
city: Jacksonville
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Crestview Hills
country: United States
state: Kentucky
city: New Orleans
country: United States
state: Louisiana
city: Saint Paul
country: United States
state: Minnesota
city: Germantown
country: United States
state: Tennessee
city: Houston
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Falls Church
country: United States
state: Virginia
city: Buenos Aires
country: Argentina
city: Rosario, Santa Fe
country: Argentina
city: Wien
country: Austria
city: Antwerpen
country: Belgium
city: Brugge
country: Belgium
city: Brussels
country: Belgium
city: Brussel
country: Belgium
city: Gent
country: Belgium
city: Leuven
country: Belgium
city: Salvador
country: Brazil
city: Sao Paulo
country: Brazil
city: São Paulo
country: Brazil
city: Plovdiv
country: Bulgaria
city: Sofia
country: Bulgaria
city: Clichy
country: France
city: Creteil N/A
country: France
city: Nice N/A
country: France
city: Paris
country: France
city: Vandoeuvre Les Nancy
country: France
city: Berlin
country: Germany
city: Düsseldorf
country: Germany
city: Freiburg
country: Germany
city: Halle (Saale)
country: Germany
city: Hannover
country: Germany
city: Kiel
country: Germany
city: Leipzig
country: Germany
city: Munchen
country: Germany
city: Münster
country: Germany
city: Ulm
country: Germany
city: Amsterdam Zuidoost
country: Netherlands
city: Leiden
country: Netherlands
city: Bialystok
country: Poland
city: Bydgoszcz
country: Poland
city: Chorzow
country: Poland
city: Czeladz
country: Poland
city: Kielce
country: Poland
city: Krakow
country: Poland
city: Warszawa
country: Poland
city: Coimbra
country: Portugal
city: Lisboa
country: Portugal
city: Porto
country: Portugal
city: Santurce
country: Puerto Rico
city: Bratislava
country: Slovakia
city: Martin
country: Slovakia
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Sevilla N/A
country: Spain
city: Valencia
country: Spain
city: Ankara
country: Turkey
city: Istanbul
country: Turkey
city: Izmir
country: Turkey
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: Manns M, Marcellin P, Poordad F, de Araujo ES, Buti M, Horsmans Y, Janczewska E, Villamil F, Scott J, Peeters M, Lenz O, Ouwerkerk-Mahadevan S, De La Rosa G, Kalmeijer R, Sinha R, Beumont-Mauviel M. Simeprevir with pegylated interferon alfa 2a or 2b plus ribavirin in treatment-naive patients with chronic hepatitis C virus genotype 1 infection (QUEST-2): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2014 Aug 2;384(9941):414-26. doi: 10.1016/S0140-6736(14)60538-9. Epub 2014 Jun 4.