Clinical trial NCT00980330: A Safety and Effectiveness Study of TMC435 in Chronic, Genotype 1, Hepatitis C Patients Who Failed to Previous Standard 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 PegIFNa-2a and Ribavirin in HCV Genotype 1 Infected Subjects Who Failed Previous Standard Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatitis C
Keywords: Hepatitis C
Peginterferon alpha-2a
PegIFNalpha-2a
RBV
Ribavirin
Placebo
TMC435-TIDP16-C206
TMC435-C206
TMC435
HCV
Lead sponsor: Tibotec Pharmaceuticals, Ireland
Sponsor class: INDUSTRY
First posted: 2009-09-21
Enrollment: 463
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 determine the efficacy, safety and tolerability of different regimens of TMC435 with standard treatment compared to standard treatment alone in participants with chronic, genotype 1, hepatitis C virus (HCV) infection who has failed previous treatment with pegylated interferon (Peg-INF-alfa-2a) and ribavirin (RBV).

Detailed description: The study is a randomized (study drug assigned by chance), double-blind (neither physician nor participant knows the name of the assigned drug), placebo-controlled Phase IIb trial with TMC435 in participants with chronic, genotype 1, hepatitis C virus (HCV) infection who have failed standard treatment with pegylated interferon (Peg-INF-alfa-2a) and ribavirin (RBV). The study will compare the efficacy, tolerability and safety of different regimens with TMC435 combined with standard treatment (Peg-INF-alfa-2a and RBV) versus standard treatment alone. The trial will consist of a screening period of maximum 6 weeks, a 48-week treatment period, and a 24-week follow-up period. Participants will be eligible to enroll in the trial if they failed to respond to a prior course of standard treatment or relapsed following standard treatment. Participants will be randomly assigned to receive TMC435 with standard treatment for 12 weeks followed by standard treatment (plus placebo) for 36 weeks, TMC435 (100 mg or 150 mg once a day) with standard treatment for 24 weeks followed by standard treatment (plus placebo) for 24 weeks, TMC435 (100 mg or 150 mg once a day) with standard treatment for 48 weeks, or a placebo with standard treatment for 48 weeks.

Eligibility criteria: Inclusion Criteria:

* Must have chronic hepatitis C infection as evidenced by liver biopsy, anti-hepatitis C virus (HCV) and HCV RNA positive
* Must have chronic hepatitis C infection (genotype 1) with HCV RNA level greater than10000 IU/mL
* Patient must have failed at least 1 prior course of peg interferon (Peg-IFN-alfa-2a)/ribavirin (RBV) therapy (standard treatment)
* Must be willing to use 2 effective methods of birth control for up to 7 months after last dose of study medication

Exclusion Criteria:

* Has an evidence of decompensated liver disease
* Co-infection with any other Hepatitis C virus genotype or co-infection with the human immunodeficiency virus (HIV)
* Has a medical condition which is a contraindication to Peg-INF or RBV therapy
* Have had 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 the End of Treatment (EOT) and 24 Weeks After the EOT (SVR24)
timeFrame: Week 72
Secondary outcomes:
measure: The Percentage of Participants With a Greater Than 2 log10 Drop in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels at Time Points During Treatment
timeFrame: Weeks, 2, 4, 8, and 12
measure: The Percentage of Participants Achieving Plasma Levels of Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <25 IU/mL Undetectable During Treatment and Follow-up
timeFrame: Weeks, 2, 4, 8, 12, 24, 36, 48, 60, 72 and EOT (up to Week 48)
measure: The Percentage of Participants Achieving Plasma Levels of Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <25 IU/mL Detectable or Undetectable During Treatment and Follow-up
timeFrame: Weeks, 2, 4, 8, 12, 24, 36, 48, 60, 72, and EOT (up to Week 48)
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: 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: Week 60
measure: The Percentage of Participants With Viral Breakthrough
timeFrame: EOT (up to Week 48)
measure: The Percentage of Participants With Viral Relapse
timeFrame: Up to Week 72
measure: The Number of Participants Who Achieved Normalized Alanine Aminotransferase (ALT) Levels at the End of Treatment (EOT)
timeFrame: EOT (up to Week 48)
measure: Plasma Concentrations of TMC435
timeFrame: 0 (predose, baseline) and 4, 8, 12, and 24 hours post-dose at Weeks 2, 4, 8, 12, 16, 24, and 48
measure: Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC24h) for TMC435
timeFrame: 0 (predose, baseline) and 4, 8, 12, and 24 hours post-dose at Weeks 2, 4, 8, 12, 16, 24, and 48
Other outcomes:
Locations:
city: La Jolla
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Jacksonville
country: United States
state: Florida
city: Miami
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: Laurel
country: United States
state: Maryland
city: Jackson
country: United States
state: Mississippi
city: Tupelo
country: United States
state: Mississippi
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: Nashville
country: United States
state: Tennessee
city: San Antonio
country: United States
state: Texas
city: Concord
country: Australia
city: Darlinghurst
country: Australia
city: Fitzroy
country: Australia
city: Melbourne
country: Australia
city: New Lambton Heights
country: Australia
city: Parkville
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: 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
country: France
city: Paris Cedex 12
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: Hannover
country: Germany
city: Köln
country: Germany
city: Stuttgart
country: Germany
city: Würzburg
country: Germany
city: Haifa
country: Israel
city: Jerusalem
country: Israel
city: Nazareth
country: Israel
city: Petah Tiqva
country: Israel
city: Ramat-Gan
country: Israel
city: Tel-Aviv
country: Israel
city: Zefat
country: Israel
city: Auckland
country: New Zealand
city: Christchurch
country: New Zealand
city: Hamilton
country: New Zealand
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: Warszawa
country: Poland
city: Coimbra
country: Portugal
city: Lisboa
country: Portugal
city: Porto
country: Portugal
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: London
country: United Kingdom
city: Plymouth
country: United Kingdom
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: Zeuzem S, Berg T, Gane E, Ferenci P, Foster GR, Fried MW, Hezode C, Hirschfield GM, Jacobson I, Nikitin I, Pockros PJ, Poordad F, Scott J, Lenz O, Peeters M, Sekar V, De Smedt G, Sinha R, Beumont-Mauviel M. Simeprevir increases rate of sustained virologic response among treatment-experienced patients with HCV genotype-1 infection: a phase IIb trial. Gastroenterology. 2014 Feb;146(2):430-41.e6. doi: 10.1053/j.gastro.2013.10.058. Epub 2013 Nov 1.