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

NCT ID: NCT00882908

Last Updated: 2014-06-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 386 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-06-30
• Study Completion Date: 2011-04-30

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.

Conditions

Hepatitis C

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

TMC435 75 mg 12 Wks + PR 24/48

Participants will receive TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo once daily and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.

Group Type: EXPERIMENTAL

TMC435

Intervention Type: DRUG

TMC435 will be administered as one or two 75 mg capsules orally, once daily, for 12 or 24 weeks.

Ribavirin (R)

Intervention Type: DRUG

Ribavirin (R) will be administered as 200 mg tablets (5 to 6 tablets) orally, twice daily, for 48 weeks.

PegIFNα-2a (P)

Intervention Type: DRUG

PegIFNα-2a (P) 180 micrograms will be administered as a subcutaneous (under the skin) injection, once weekly for 48 weeks.

Placebo

Intervention Type: DRUG

Placebo capsules identical in appearance to TMC435 capsule will be administered orally, once daily, for 48 weeks.

TMC435 75 mg 24 Wks + PR 24/48

Participants will receive TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.

Group Type: EXPERIMENTAL

TMC435

Intervention Type: DRUG

TMC435 will be administered as one or two 75 mg capsules orally, once daily, for 12 or 24 weeks.

Ribavirin (R)

Intervention Type: DRUG

Ribavirin (R) will be administered as 200 mg tablets (5 to 6 tablets) orally, twice daily, for 48 weeks.

PegIFNα-2a (P)

Intervention Type: DRUG

PegIFNα-2a (P) 180 micrograms will be administered as a subcutaneous (under the skin) injection, once weekly for 48 weeks.

Placebo

Intervention Type: DRUG

Placebo capsules identical in appearance to TMC435 capsule will be administered orally, once daily, for 48 weeks.

TMC435 150 mg 12 Wks + PR 24/48

Participants will receive TMC435 150 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed Placebo and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.

Group Type: EXPERIMENTAL

TMC435

Intervention Type: DRUG

TMC435 will be administered as one or two 75 mg capsules orally, once daily, for 12 or 24 weeks.

Ribavirin (R)

Intervention Type: DRUG

Ribavirin (R) will be administered as 200 mg tablets (5 to 6 tablets) orally, twice daily, for 48 weeks.

PegIFNα-2a (P)

Intervention Type: DRUG

PegIFNα-2a (P) 180 micrograms will be administered as a subcutaneous (under the skin) injection, once weekly for 48 weeks.

Placebo

Intervention Type: DRUG

Placebo capsules identical in appearance to TMC435 capsule will be administered orally, once daily, for 48 weeks.

TMC435 150 mg 24 Wks + PR 24/48

Participants will receive TMC435 150 mg once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.

Group Type: EXPERIMENTAL

TMC435

Intervention Type: DRUG

TMC435 will be administered as one or two 75 mg capsules orally, once daily, for 12 or 24 weeks.

Ribavirin (R)

Intervention Type: DRUG

Ribavirin (R) will be administered as 200 mg tablets (5 to 6 tablets) orally, twice daily, for 48 weeks.

PegIFNα-2a (P)

Intervention Type: DRUG

PegIFNα-2a (P) 180 micrograms will be administered as a subcutaneous (under the skin) injection, once weekly for 48 weeks.

Placebo

Intervention Type: DRUG

Placebo capsules identical in appearance to TMC435 capsule will be administered orally, once daily, for 48 weeks.

Placebo 24 Wks + PR48

Participants will receive Placebo once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks followed by PR until Week 48.

Group Type: PLACEBO_COMPARATOR

Ribavirin (R)

Intervention Type: DRUG

Ribavirin (R) will be administered as 200 mg tablets (5 to 6 tablets) orally, twice daily, for 48 weeks.

PegIFNα-2a (P)

Intervention Type: DRUG

PegIFNα-2a (P) 180 micrograms will be administered as a subcutaneous (under the skin) injection, once weekly for 48 weeks.

Placebo

Intervention Type: DRUG

Placebo capsules identical in appearance to TMC435 capsule will be administered orally, once daily, for 48 weeks.

Interventions

TMC435

TMC435 will be administered as one or two 75 mg capsules orally, once daily, for 12 or 24 weeks.

Intervention Type: DRUG

Ribavirin (R)

Ribavirin (R) will be administered as 200 mg tablets (5 to 6 tablets) orally, twice daily, for 48 weeks.

Intervention Type: DRUG

PegIFNα-2a (P)

PegIFNα-2a (P) 180 micrograms will be administered as a subcutaneous (under the skin) injection, once weekly for 48 weeks.

Intervention Type: DRUG

Placebo

Placebo capsules identical in appearance to TMC435 capsule will be administered orally, once daily, for 48 weeks.

Intervention Type: DRUG

Other Intervention Names

TMC 435; COPEGUS; PEGASYS

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tibotec Pharmaceuticals, Ireland

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tibotec Pharmaceuticals, Ireland Clinical Trial

Role: STUDY_DIRECTOR

Tibotec Pharmaceuticals, Ireland

Locations

Los Angeles, California, United States

Jacksonville, Florida, United States

Orlando, Florida, United States

Palm Harbor, Florida, United States

Chicago, Illinois, United States

New Orleans, Louisiana, United States

Saint Paul, Minnesota, United States

New York, New York, United States

Chapel Hill, North Carolina, United States

Cincinnati, Ohio, United States

Germantown, Tennessee, United States

Charlottesville, Virginia, United States

Concord, , Australia

Darlinghurst, , Australia

Fitzroy, , Australia

Melbourne, , Australia

Sydney, , Australia

Woolloongabba, , Australia

Vienna, , Austria

Bruges, , Belgium

Brussels, , Belgium

Edegem, , Belgium

Ghent, , Belgium

Leuven, , Belgium

Roeselare, , Belgium

Calgary, Alberta, Canada

Toronto, Ontario, Canada

Montreal, Quebec, Canada

Aarhus, , Denmark

Copenhagen, , Denmark

Hvidovre, , Denmark

Kolding, , Denmark

Odense, , Denmark

Clichy, , France

Créteil, , France

Grenoble, , France

Lyon, , France

Nice, , France

Paris, , France

Vandœuvre-lès-Nancy, , France

Berlin, , Germany

Cologne, , Germany

Düsseldorf, , Germany

Frankfurt A. M., , Germany

Freiburg im Breisgau, , Germany

Hamburg, , Germany

Hanover, , Germany

Stuttgart, , Germany

Würzburg, , Germany

Auckland, , New Zealand

Christchurch, , New Zealand

Hamilton, , New Zealand

Bergen, , Norway

Nordbyhagen, , Norway

Oslo, , Norway

Tromsø, , Norway

Bialystok, , Poland

Bydgoszcz, , Poland

Czeladź, , Poland

Kielce, , Poland

Lodz, , Poland

Warsaw, , Poland

Moscow, , Russia

Nizhny Novgorod, , Russia

Saint Petersburg, , Russia

Samara, , Russia

Smolensk, , Russia

Barcelona, , Spain

Madrid, , Spain

Seville, , Spain

Valencia, , Spain

Countries

United States; Australia; Austria; Belgium; Canada; Denmark; France; Germany; New Zealand; Norway; Poland; Russia; Spain

References

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.

Reference Type: DERIVED

PMID: 25445400 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 25164700 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 23907700 (View on PubMed)

Other Identifiers

TMC435-TiDP16-C205

Identifier Type: OTHER

Identifier Source: secondary_id

2008-007147-13

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR015799

Identifier Type: -

Identifier Source: org_study_id