Clinical trial NCT01281839: An Efficacy, Safety and Tolerability Study of TMC435 in Genotype 1 Hepatitis C-infected Patients Who Relapsed After Previous Therapy
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 Hepatitis C, Genotype 1 Infected Subjects Who Relapsed After Previous Interferon-based Therapy
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: 2011-01-24
Enrollment: 394
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 patients who are infected with genotype 1 hepatitis C virus who relapsed after previous interferon-based therapy. Patients will also receive peginterferon alfa-2a and ribavirin as part of their treatment.

Detailed description: This is a randomized, double-blind (neither physician nor patients knows the name of the assigned drug), placebo-controlled study of TMC435 in patients who are infected with genotype 1 hepatitis C virus who relapsed after previous interferon-based therapy. Patients in this study will also receive two other drugs for their infection called peginterferon alfa-2a and ribavirin. 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, patients will take TMC435 or placebo, plus peginterferon alfa-2a and ribavirin. For the next 12 weeks, patients will take peginterferon alfa-2a and ribavirin only. After that, some patients will continue to take peginterferon alfa-2a and ribavirin for up to 24 additional weeks. Other patients will stop taking peginterferon alfa-2a and ribavirin. The study doctor will inform each patient about how to take their study medication and when they should stop taking it. After a patient 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). Patients 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, ECG assessments (a measurement of the electrical activity of your heart), patient 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. Ribavirin (Copegus ®) will be taken as a tablet twice each day and the dose will depend on your body weight.

Eligibility criteria: Inclusion Criteria:

* Genotype 1 hepatitis C infection (confirmed at screening)
* Have previously received peginterferon-based therapy for at least 24 weeks with documented HCV RNA at last measurement and relapsed within 1 year of last taking medication
* 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: The 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 Week 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: The Percentage of Participants With Null Response
timeFrame: Week 12
measure: The Percentage of Participants With Partial Response
timeFrame: Week 12
measure: The Percentage of Participants With Viral Breakthrough
timeFrame: Up to Week 48
measure: The Percentage of Participants With Viral Relapse
timeFrame: Up to Week 72
measure: The Percentage of Participants Who Completed All Study Treatment at Week 24 Because of the Treatment Duration Rule
timeFrame: Week 24
measure: The 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
timeFrame: Up to 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) <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: From the time of administration up to 24 hours after dosing through Week 12
measure: Plasma Concentration of TMC435: Predose Plasma Concentration (C0h)
timeFrame: Before administration of TMC435 through Week 12
measure: Plasma Concentration of TMC435: Systemic Clearance (CL)
timeFrame: From the time of administration through Week 12
Other outcomes:
Locations:
city: Bakersfield
country: United States
state: California
city: Aurora
country: United States
state: Colorado
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: Saint Paul
country: United States
state: Minnesota
city: Jackson
country: United States
state: Mississippi
city: Germantown
country: United States
state: Tennessee
city: Houston
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Adelaide
country: Australia
city: Kingswood
country: Australia
city: Melbourne
country: Australia
city: Sydney
country: Australia
city: Woolloongabba N/A
country: Australia
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: Vancouver
country: Canada
state: British Columbia
city: Ottawa
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Creteil N/A
country: France
city: Grenoble
country: France
city: Lyon
country: France
city: Nice N/A
country: France
city: Paris Cedex 12
country: France
city: Paris
country: France
city: Rennes Cedex
country: France
city: Vandoeuvre Les Nancy
country: France
city: Berlin
country: Germany
city: Düsseldorf
country: Germany
city: Frankfurt
country: Germany
city: Freiburg
country: Germany
city: Halle (Saale)
country: Germany
city: Hamburg
country: Germany
city: Kiel
country: Germany
city: Leipzig
country: Germany
city: Munchen
country: Germany
city: Würzburg
country: Germany
city: Auckland
country: New Zealand
city: Christchurch
country: New Zealand
city: Hamilton
country: New Zealand
city: Bialystok
country: Poland
city: Bydgoszcz
country: Poland
city: Czeladz
country: Poland
city: Kielce
country: Poland
city: Krakow
country: Poland
city: Warszawa
country: Poland
city: Ponce Pr
country: Puerto Rico
city: San Juan
country: Puerto Rico
city: Moscow
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: Stavropol
country: Russian Federation
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Sevilla N/A
country: Spain
city: Valencia
country: Spain
city: Birmingham
country: United Kingdom
city: Derby
country: United Kingdom
city: Glasgow
country: United Kingdom
city: London
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: Forns X, Lawitz E, Zeuzem S, Gane E, Bronowicki JP, Andreone P, Horban A, Brown A, Peeters M, Lenz O, Ouwerkerk-Mahadevan S, Scott J, De La Rosa G, Kalmeijer R, Sinha R, Beumont-Mauviel M. Simeprevir with peginterferon and ribavirin leads to high rates of SVR in patients with HCV genotype 1 who relapsed after previous therapy: a phase 3 trial. Gastroenterology. 2014 Jun;146(7):1669-79.e3. doi: 10.1053/j.gastro.2014.02.051. Epub 2014 Mar 3.