A Safety and Effectiveness Study of TMC435 in Chronic, Genotype 1, Hepatitis C Patients Who Failed to Previous Standard Treatment

NCT ID: NCT00980330

Last Updated: 2014-06-09

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

463 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-10-31

Study Completion Date

2011-08-31

Brief Summary

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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

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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.

Conditions

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Hepatitis C

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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TMC435 100 mg 12 Wks + PR48

Participants will receive TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo with PR for 36 weeks.

Group Type EXPERIMENTAL

TMC435

Intervention Type DRUG

One TMC435 100-mg capsule or two 75-mg capsules orally (by mouth) once daily for 12, 24, or 48 weeks.

Placebo

Intervention Type DRUG

One or 2 capsules of placebo identical in appearance to TMC435 taken orally once daily for 24, 36, or 48 weeks.

Peg-IFN-alfa-2a (P)

Intervention Type DRUG

180 micrograms taken as one 0.5 mL subcutaneous injection once weekly for 48 weeks.

Ribavirin (R)

Intervention Type DRUG

1000 or 1200 mg/day (5 or 6 tablets) taken orally as a twice daily regimen taken for 48 weeks.

TMC435 100 mg 24 Wks + PR48

Participants willl receive TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks followed by Placebo with PR for 24 weeks.

Group Type EXPERIMENTAL

TMC435

Intervention Type DRUG

One TMC435 100-mg capsule or two 75-mg capsules orally (by mouth) once daily for 12, 24, or 48 weeks.

Placebo

Intervention Type DRUG

One or 2 capsules of placebo identical in appearance to TMC435 taken orally once daily for 24, 36, or 48 weeks.

Peg-IFN-alfa-2a (P)

Intervention Type DRUG

180 micrograms taken as one 0.5 mL subcutaneous injection once weekly for 48 weeks.

Ribavirin (R)

Intervention Type DRUG

1000 or 1200 mg/day (5 or 6 tablets) taken orally as a twice daily regimen taken for 48 weeks.

TMC435 100 mg 48 Wks + PR48

Participants will receive TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 48 weeks.

Group Type EXPERIMENTAL

TMC435

Intervention Type DRUG

One TMC435 100-mg capsule or two 75-mg capsules orally (by mouth) once daily for 12, 24, or 48 weeks.

Placebo

Intervention Type DRUG

One or 2 capsules of placebo identical in appearance to TMC435 taken orally once daily for 24, 36, or 48 weeks.

Peg-IFN-alfa-2a (P)

Intervention Type DRUG

180 micrograms taken as one 0.5 mL subcutaneous injection once weekly for 48 weeks.

Ribavirin (R)

Intervention Type DRUG

1000 or 1200 mg/day (5 or 6 tablets) taken orally as a twice daily regimen taken for 48 weeks.

TMC435 150 mg 12 Wks + PR48

Participants will receive TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo and PR for 36 weeks.

Group Type EXPERIMENTAL

TMC435

Intervention Type DRUG

One TMC435 100-mg capsule or two 75-mg capsules orally (by mouth) once daily for 12, 24, or 48 weeks.

Placebo

Intervention Type DRUG

One or 2 capsules of placebo identical in appearance to TMC435 taken orally once daily for 24, 36, or 48 weeks.

Peg-IFN-alfa-2a (P)

Intervention Type DRUG

180 micrograms taken as one 0.5 mL subcutaneous injection once weekly for 48 weeks.

Ribavirin (R)

Intervention Type DRUG

1000 or 1200 mg/day (5 or 6 tablets) taken orally as a twice daily regimen taken for 48 weeks.

TMC435 150 mg 24 Wks + PR48

Participants will receive TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks followed Placebo and PR for 24 weeks.

Group Type EXPERIMENTAL

TMC435

Intervention Type DRUG

One TMC435 100-mg capsule or two 75-mg capsules orally (by mouth) once daily for 12, 24, or 48 weeks.

Placebo

Intervention Type DRUG

One or 2 capsules of placebo identical in appearance to TMC435 taken orally once daily for 24, 36, or 48 weeks.

Peg-IFN-alfa-2a (P)

Intervention Type DRUG

180 micrograms taken as one 0.5 mL subcutaneous injection once weekly for 48 weeks.

Ribavirin (R)

Intervention Type DRUG

1000 or 1200 mg/day (5 or 6 tablets) taken orally as a twice daily regimen taken for 48 weeks.

TMC435 150 mg 48 Wks + PR48

Participants will receive TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 48 weeks.

Group Type EXPERIMENTAL

TMC435

Intervention Type DRUG

One TMC435 100-mg capsule or two 75-mg capsules orally (by mouth) once daily for 12, 24, or 48 weeks.

Peg-IFN-alfa-2a (P)

Intervention Type DRUG

180 micrograms taken as one 0.5 mL subcutaneous injection once weekly for 48 weeks.

Ribavirin (R)

Intervention Type DRUG

1000 or 1200 mg/day (5 or 6 tablets) taken orally as a twice daily regimen taken for 48 weeks.

Placebo 48 Wks + PR48

Participants will receive Placebo once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 48 weeks.

Group Type PLACEBO_COMPARATOR

TMC435

Intervention Type DRUG

One TMC435 100-mg capsule or two 75-mg capsules orally (by mouth) once daily for 12, 24, or 48 weeks.

Peg-IFN-alfa-2a (P)

Intervention Type DRUG

180 micrograms taken as one 0.5 mL subcutaneous injection once weekly for 48 weeks.

Ribavirin (R)

Intervention Type DRUG

1000 or 1200 mg/day (5 or 6 tablets) taken orally as a twice daily regimen taken for 48 weeks.

Interventions

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TMC435

One TMC435 100-mg capsule or two 75-mg capsules orally (by mouth) once daily for 12, 24, or 48 weeks.

Intervention Type DRUG

Placebo

One or 2 capsules of placebo identical in appearance to TMC435 taken orally once daily for 24, 36, or 48 weeks.

Intervention Type DRUG

Peg-IFN-alfa-2a (P)

180 micrograms taken as one 0.5 mL subcutaneous injection once weekly for 48 weeks.

Intervention Type DRUG

Ribavirin (R)

1000 or 1200 mg/day (5 or 6 tablets) taken orally as a twice daily regimen taken for 48 weeks.

Intervention Type DRUG

Other Intervention Names

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PEGASYS COPEGUS

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Tibotec Pharmaceuticals, Ireland

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Tibotec Pharmaceuticals, Ireland Clinical Trial

Role: STUDY_DIRECTOR

Tibotec Pharmaceuticals, Ireland

Locations

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La Jolla, California, United States

Site Status

Los Angeles, California, United States

Site Status

Jacksonville, Florida, United States

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Miami, Florida, United States

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Orlando, Florida, United States

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Palm Harbor, Florida, United States

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Chicago, Illinois, United States

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New Orleans, Louisiana, United States

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Laurel, Maryland, United States

Site Status

Jackson, Mississippi, United States

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Tupelo, Mississippi, United States

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New York, New York, United States

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Chapel Hill, North Carolina, United States

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Cincinnati, Ohio, United States

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Germantown, Tennessee, United States

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Nashville, Tennessee, United States

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San Antonio, Texas, United States

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Concord, , Australia

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Darlinghurst, , Australia

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Fitzroy, , Australia

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Melbourne, , Australia

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New Lambton Heights, , Australia

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Parkville, , Australia

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Sydney, , Australia

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Woolloongabba, , Australia

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Vienna, , Austria

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Bruges, , Belgium

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Brussels, , Belgium

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Edegem, , Belgium

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Ghent, , Belgium

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Leuven, , Belgium

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Roeselare, , Belgium

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Calgary, Alberta, Canada

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Ottawa, Ontario, Canada

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Toronto, Ontario, Canada

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Montreal, Quebec, Canada

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Créteil, , France

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Grenoble, , France

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Lyon, , France

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Nice, , France

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Paris, , France

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Vandœuvre-lès-Nancy, , France

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Berlin, , Germany

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Cologne, , Germany

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Düsseldorf, , Germany

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Frankfurt A. M., , Germany

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Freiburg im Breisgau, , Germany

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Hanover, , Germany

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Stuttgart, , Germany

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Würzburg, , Germany

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Haifa, , Israel

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Jerusalem, , Israel

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Nazareth, , Israel

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Petah Tikva, , Israel

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Ramat Gan, , Israel

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Safed, , Israel

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Tel Aviv, , Israel

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Auckland, , New Zealand

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Christchurch, , New Zealand

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Hamilton, , New Zealand

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Nordbyhagen, , Norway

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Oslo, , Norway

Site Status

Tromsø, , Norway

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Bialystok, , Poland

Site Status

Bydgoszcz, , Poland

Site Status

Czeladź, , Poland

Site Status

Kielce, , Poland

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Warsaw, , Poland

Site Status

Coimbra, , Portugal

Site Status

Lisbon, , Portugal

Site Status

Porto, , Portugal

Site Status

Moscow, , Russia

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Nizhny Novgorod, , Russia

Site Status

Saint Petersburg, , Russia

Site Status

Samara, , Russia

Site Status

Smolensk, , Russia

Site Status

London, , United Kingdom

Site Status

Plymouth, , United Kingdom

Site Status

Countries

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United States Australia Austria Belgium Canada France Germany Israel New Zealand Norway Poland Portugal Russia United Kingdom

References

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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)

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.

Reference Type DERIVED
PMID: 24184810 (View on PubMed)

Other Identifiers

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TMC435-TiDP16-C206

Identifier Type: OTHER

Identifier Source: secondary_id

2009-010590-20

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR016063

Identifier Type: -

Identifier Source: org_study_id

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