Clinical trial NCT00882908: A Study of TMC435 in Combination With Pegylated Interferon Alp\Fa-2a and Ribavirin in Patients Infected With Genotype 1 Hepatitis C Virus Who Never Received Treatment
Official title: A Phase IIb, Randomized, Double-Blind, Placebo-Controlled Trial to Investigate the Efficacy, Tolerability, Safety and Pharmacokinetics of TMC435 as Part of a Treatment Regimen Including Peginterferon Alfa-2a and Ribavirin In Treatment-Naive Genotype 1 Hepatitis C-Infected Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatitis C
Keywords: Hepatitis C
TMC435
Peginterferon alpha-2a
PegIFNalpha-2a
RBV
Ribavirin
Placebo
Lead sponsor: Tibotec Pharmaceuticals, Ireland
Sponsor class: INDUSTRY
First posted: 2009-04-17
Enrollment: 386
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
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 evaluate the efficacy of 4 different regimens of TMC435 in combination with peginterferon alfa-2a (PegIFNα-2a) and ribavirin (RBV), defined as the proportion of patients with sustained virologic response at Week 72 (patients with undetectable plasma HCV RNA \[less than 25 IU per mL undetectable\] at the end of treatment and at Week 72), compared to the control group receiving PegIFN and RBV in combination with TMC435-matched placebo.

Detailed description: This is a randomized (study medication assigned by chance), 5-arm, double-blind (neither investigator nor the participant knows the treatment that the participant receives), placebo-controlled (an inactive substance that is compared with the study medication to test whether the study medication has a real effect in clinical study) study to compare the efficacy, tolerability and safety of different TMC435 regimens combined with peginterferon alfa-2a (PegIFNα-2a) and ribavirin (RBV) versus PegIFNα-2a plus RBV alone in adult treatment-naive patients with chronic genotype 1 HCV infection. The study mainly consists of 3 phases: screening phase (approximately 6 weeks), treatment phase (up to 48 weeks), and follow up phase (up to 48 weeks). In the treatment phase, patients will be divided in to 5 different arms in a 1:1:1:1:1 randomized ratio. In treatment arms 1 and 2, patients will receive 12 weeks of therapy with TMC435 along with PegIFNα 2a and RBV followed by treatment with PegIFNα 2a, RBV, and TMC435-matched placebo. In treatment arms 3 and 4, patients will receive 24 weeks of therapy with TMC435, PegIFNα 2a, and RBV. In treatment arm 5 (control group), patients will receive PegIFNα 2a and RBV for 48 weeks and TMC435 matched placebo for the first 24 weeks. Collection of blood samples for efficacy evaluations will be done at scheduled visits throughout the study. Safety evaluations for adverse events, clinical laboratory tests, physical examination, vital signs and electrocardiogram will be monitored throughout the study. The total duration of the study will be up to approximately 72 weeks after initiation of treatment.

Eligibility criteria: Inclusion Criteria:

* Patients with documented chronic genotype-1 hepatitis C infection and with plasma HCV RNA of \> 100,000 IU/mL at screening
* Patients that have not been treated before for HCV
* Patients that are of childbearing potential or have a partner of childbearing potential should agree to use 2 effective methods of contraception

Exclusion Criteria:

* Patients with cirrhosis or evidence of hepatic decompensation
* Co-infection with the human immunodeficiency virus (HIV)
* Any contraindication to Pegasys or Copegus therapy
* History of, or any current medical condition which could impact the safety of the patient in the study

Primary outcomes:
measure: The Percentage of Participants Achieving a Sustained Virologic Response at Week 72 (SVRW72)
timeFrame: Week 72
Secondary outcomes:
measure: The Percentage of Participants Achieving Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels of Less Than 25 IU/mL Undetectable During Treatment and Follow-up
timeFrame: Weeks, 2, 4, 8, 12, 24, 36, 48, 60, 72, and at EOT (up to Week 24 or 48)
measure: The Percentage of Participants Who Achieved Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels of Less Than 25 IU/mL Detectable or Undetectable During Treatment and Follow-up
timeFrame: Weeks 2, 4, 8, 12, 24, 36, 48, 60, 72, and at EOT (up to Week 24 or 48)
measure: The Percentage of Participants Achieving Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels of Greater Than or Equal to 2 log10 Drop During Treatment
timeFrame: Baseline (Day 1) and Weeks, 2, 4, 8, and 12
measure: The Percentage of Participants Who Achieved a Sustained Virologic Response 24 Weeks After the Planned End of Treatment (SVR24)
timeFrame: Week 48 or 72
measure: The Percentage of Participants Achieving a Rapid Virologic Response (RVR)
timeFrame: Week 4
measure: The Percentage of Participants Achieving an Early Virologic Response (EVR)
timeFrame: Baseline (Day 1) and Week 12
measure: The Percentage of Participants Achieving a Complete Early Virologic Response (cEVR)
timeFrame: Week 12
measure: The Percentage of Participants Achieving a Sustained Virologic Response 12 Weeks After the Planned End of Treatment (SVR12)
timeFrame: Up to Week 36 or 52
measure: Number of Participants With Viral Breakthrough
timeFrame: Week 24 or 48
measure: The Number of Participants With Viral Relapse
timeFrame: Up to Week 72
measure: The Number of Participants With Abnormal Alanine Aminotransferase (ALT) Levels at Baseline Who Achieved Normalized ALT Levels at the End of Treatment (EOT)
timeFrame: Baseline (Day 1) up to Week 24 or 48
measure: Plasma Concentrations of TMC435
timeFrame: Two random blood samples taken at least 2 hours apart at Weeks 2, 4, 8, 12, 16, and 24
measure: Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC24h) for TMC435
timeFrame: Two random blood samples taken at least 2 hours apart at Weeks 2, 4, 8, 12, 16, and 24
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: Palm Harbor
country: United States
state: Florida
city: Chicago
country: United States
state: Illinois
city: New Orleans
country: United States
state: Louisiana
city: Saint Paul
country: United States
state: Minnesota
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: Germantown
country: United States
state: Tennessee
city: Charlottesville
country: United States
state: Virginia
city: Concord
country: Australia
city: Darlinghurst
country: Australia
city: Fitzroy
country: Australia
city: Melbourne
country: Australia
city: Sydney
country: Australia
city: Woolloongabba N/A
country: Australia
city: Wien
country: Austria
city: Brugge
country: Belgium
city: Brussels
country: Belgium
city: Bruxelles
country: Belgium
city: Edegem
country: Belgium
city: Gent
country: Belgium
city: Leuven
country: Belgium
city: Roeselare
country: Belgium
city: Calgary
country: Canada
state: Alberta
city: Toronto
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Aarhus
country: Denmark
city: Copenhagen
country: Denmark
city: Hvidovre N/A
country: Denmark
city: Kolding
country: Denmark
city: Odense N/A
country: Denmark
city: Clichy
country: France
city: Creteil N/A
country: France
city: Grenoble
country: France
city: Lyon
country: France
city: Nice
country: France
city: Paris
country: France
city: Vandoeuvre Les Nancy
country: France
city: Berlin
country: Germany
city: Düsseldorf
country: Germany
city: Frankfurt A. M.
country: Germany
city: Freiburg
country: Germany
city: Hamburg
country: Germany
city: Hannover
country: Germany
city: Köln
country: Germany
city: Stuttgart
country: Germany
city: Würzburg
country: Germany
city: Auckland
country: New Zealand
city: Christchurch
country: New Zealand
city: Hamilton
country: New Zealand
city: Bergen
country: Norway
city: Nordbyhagen
country: Norway
city: Oslo
country: Norway
city: Tromsø
country: Norway
city: Bialystok
country: Poland
city: Bydgoszcz
country: Poland
city: Czeladz
country: Poland
city: Kielce
country: Poland
city: Lodz
country: Poland
city: Warschau
country: Poland
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
Study officials:
affiliation: Tibotec Pharmaceuticals, Ireland
name: Tibotec Pharmaceuticals, 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: Scott J, Rosa K, Fu M, Cerri K, Peeters M, Beumont M, Zeuzem S, Evon DM, Gilles L. Fatigue during treatment for hepatitis C virus: results of self-reported fatigue severity in two Phase IIb studies of simeprevir treatment in patients with hepatitis C virus genotype 1 infection. BMC Infect Dis. 2014 Aug 26;14:465. doi: 10.1186/1471-2334-14-465.
citation: Fried MW, Buti M, Dore GJ, Flisiak R, Ferenci P, Jacobson I, Marcellin P, Manns M, Nikitin I, Poordad F, Sherman M, Zeuzem S, Scott J, Gilles L, Lenz O, Peeters M, Sekar V, De Smedt G, Beumont-Mauviel M. Once-daily simeprevir (TMC435) with pegylated interferon and ribavirin in treatment-naive genotype 1 hepatitis C: the randomized PILLAR study. Hepatology. 2013 Dec;58(6):1918-29. doi: 10.1002/hep.26641. Epub 2013 Oct 11.