A Safety and Effectiveness Study of Telaprevir in Chronic, Genotype 1, Hepatitis C Patients That Failed Previous Standard Treatment

NCT ID: NCT00703118

Last Updated: 2014-01-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 663 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-10-31
• Study Completion Date: 2010-07-31

Brief Summary

The purpose of this study is to determine the safety, efficacy and tolerability of using two regimens of telaprevir (with and without delayed start) with standard treatment compared to standard treatment alone in participants with chronic, genotype 1, hepatitis C.

Detailed Description

This is a randomized, double-blind, placebo-controlled Phase III trial with telaprevir in patients with chronic Hepatitis C Virus (HCV), genotype 1, infection who failed prior treatment with standard treatment. Standard treatment is defined as treatment with Peg-INF and RBV. The trial is designed to compare the efficacy, safety, and tolerability of 2 regimens of telaprevir (with and without delayed start) combined with standard treatment versus standard treatment alone. The trial will consist of a screening period of approximately 4 weeks, a 48-week treatment period, and a 24-week follow-up period. Patients will be eligible to enroll in the trial if they (1) had an undetectable HCV Ribonucleic Acid (RNA) level at the end of a prior course of standard treatment but did not achieve a response (viral relapsers), or (2) never had an undetectable HCV RNA level during or at the end of a prior course of standard treatment (non-responders). Approximately 650 patients (350 prior relapsers and 300 prior non-responders) will be randomized in a 2:2:1 ratio to one of 3 treatment groups: Treatment group A will receive telaprevir with standard treatment for 12 weeks; followed by placebo with standard treatment for 4 weeks; followed by standard treatment for 32 weeks. Treatment group B will receive placebo with standard treatment for 4 weeks; followed by telaprevir with standard treatment for 12 weeks; followed by standard treatment for 32 weeks. Treatment group C will receive placebo with standard treatment for 16 weeks; followed by standard treatment for 32 weeks. In both telaprevir regimens (A and B), patients will receive 12 weeks of 750 mg of telaprevir every 8 hours along with 48 weeks of standard treatment. Telaprevir or placebo will be given by mouth at a dose of 750 mg every 8 hours for 16 weeks. Peg-INF will be given as an injection under the skin at a dose of 180 mcg once every week for 48 weeks. RBV will be given by mouth at a dose of either 1000 or 1200 mg (depending on your body weight) two times per day for 48 weeks.

Conditions

Hepatitis C, Chronic

Study Design

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

Study Groups

Group A: T12/PR48

Participants will receive 12 weeks of 750 mg telaprevir eight hourly followed by 4 weeks of Placebo in combination with 48 weeks of Peg-IFN-alfa-2a and ribavirin at standard doses.

Group Type: EXPERIMENTAL

Telaprevir

Intervention Type: DRUG

Participants will receive telaprevir tablets of 750 mg orally eight hourly for 12 weeks in group A and B.

Peg-IFN-alfa-2a

Intervention Type: DRUG

Participants will receive 180 µg subcutaneous (under the skin) injection of Peg-IFN-alfa-2a once weekly for 48 weeks in Group A, B and C.

Ribavirin

Intervention Type: DRUG

Participants will receive ribavirin tablets of 1000-1200 mg orally twice daily for 48 weeks in Group A, B, and C.

Placebo

Intervention Type: DRUG

Participants will receive telaprevir matching placebo tablets orally for 4 weeks in Group A and B. Participants will receive telaprevir matching placebo tablets orally for 16 weeks in Group C.

Group B: T12(DS)/PR48

Participants will receive 4 weeks of Placebo followed by 12 weeks of 750 mg telaprevir eight hourly in combination with 48 weeks of Peg-IFN-alfa-2a and ribavirin at standard doses.

Group Type: EXPERIMENTAL

Telaprevir

Intervention Type: DRUG

Participants will receive telaprevir tablets of 750 mg orally eight hourly for 12 weeks in group A and B.

Peg-IFN-alfa-2a

Intervention Type: DRUG

Participants will receive 180 µg subcutaneous (under the skin) injection of Peg-IFN-alfa-2a once weekly for 48 weeks in Group A, B and C.

Ribavirin

Intervention Type: DRUG

Participants will receive ribavirin tablets of 1000-1200 mg orally twice daily for 48 weeks in Group A, B, and C.

Placebo

Intervention Type: DRUG

Participants will receive telaprevir matching placebo tablets orally for 4 weeks in Group A and B. Participants will receive telaprevir matching placebo tablets orally for 16 weeks in Group C.

Group C: Pbo/PR48

Participants will receive placebo in combination with Peg- IFN-alfa-2a and ribavirin for 16 weeks. Participants will receive Peg- IFN-alfa-2a and ribavirin for next 32 weeks.

Group Type: EXPERIMENTAL

Peg-IFN-alfa-2a

Intervention Type: DRUG

Participants will receive 180 µg subcutaneous (under the skin) injection of Peg-IFN-alfa-2a once weekly for 48 weeks in Group A, B and C.

Ribavirin

Intervention Type: DRUG

Participants will receive ribavirin tablets of 1000-1200 mg orally twice daily for 48 weeks in Group A, B, and C.

Placebo

Intervention Type: DRUG

Participants will receive telaprevir matching placebo tablets orally for 4 weeks in Group A and B. Participants will receive telaprevir matching placebo tablets orally for 16 weeks in Group C.

Interventions

Telaprevir

Participants will receive telaprevir tablets of 750 mg orally eight hourly for 12 weeks in group A and B.

Intervention Type: DRUG

Peg-IFN-alfa-2a

Participants will receive 180 µg subcutaneous (under the skin) injection of Peg-IFN-alfa-2a once weekly for 48 weeks in Group A, B and C.

Intervention Type: DRUG

Ribavirin

Participants will receive ribavirin tablets of 1000-1200 mg orally twice daily for 48 weeks in Group A, B, and C.

Intervention Type: DRUG

Placebo

Participants will receive telaprevir matching placebo tablets orally for 4 weeks in Group A and B. Participants will receive telaprevir matching placebo tablets orally for 16 weeks in Group C.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Patient must have chronic hepatitis C infection (genotype 1) with HCV RNA level >= 1000 IU/mL
• Patient must have failed at least 1 prior course of Peg-IFN/RBV therapy (standard treatment)
• Patient must be willing to use 2 effective methods of birth control for up to 7 months after last dose of study medication

Exclusion Criteria

• Patient is a previous non-responder that is classified as a viral breakthrough case
• Patient is infected with Hepatitis C virus, genotype 1, exhibiting more than one subtype
• Patient has Hepatitis C virus, genotype 1, and exhibits co-infection with any other genotype
• Evidence of decompensated liver disease
• Patient has condition that requires use of systemic corticosteroids

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

Sponsors

Tibotec Pharmaceutical Limited

INDUSTRY

Sponsor Role: collaborator

Tibotec BVBA

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tibotec-Virco Virology BVBA Clinical Trial

Role: STUDY_DIRECTOR

Tibotec BVBA

Locations

Birmingham, Alabama, United States

Coronado, California, United States

La Jolla, California, United States

Los Angeles, California, United States

San Francisco, California, United States

Aurora, Colorado, United States

Bradenton, Florida, United States

Gainesville, Florida, United States

Miami, Florida, United States

Atlanta, Georgia, United States

Indianapolis, Indiana, United States

Baltimore, Maryland, United States

Boston, Massachusetts, United States

Worcester, Massachusetts, United States

Detroit, Michigan, United States

Plymouth, Minnesota, United States

Kansas City, Missouri, United States

Egg Harbor Twp, New Jersey, United States

Albuquerque, New Mexico, United States

Manhasset, New York, United States

New York, New York, United States

Chapel Hill, North Carolina, United States

Durham, North Carolina, United States

Philadelphia, Pennsylvania, United States

Columbia, South Carolina, United States

Dallas, Texas, United States

Houston, Texas, United States

San Antonio, Texas, United States

Falls Church, Virginia, United States

Norfolk, Virginia, United States

Richmond, Virginia, United States

Adelaide, , Australia

Camperdown, , Australia

Clayton, , Australia

Darlinghurst, , Australia

Kingswood, , Australia

Melbourne, , Australia

Parkville - Vic, , Australia

Perth, , Australia

Graz, , Austria

Vienna, , Austria

Brussels, , Belgium

Ghent, , Belgium

Leuven, , Belgium

Distrito Barao Geraldo-Campina, , Brazil

Salvador, , Brazil

Santo André, , Brazil

São Paulo, , Brazil

Vancouver, British Columbia, Canada

Ottawa, Ontario, Canada

Montreal, Quebec, Canada

Clichy, , France

Créteil, , France

Grenoble, , France

Lille, , France

Lyon, , France

Marseille, , France

Paris, , France

Pessac, , France

Vandœuvre-lès-Nancy, , France

Berlin, , Germany

Cologne, , Germany

Düsseldorf, , Germany

Frankfurt, , Germany

Freiburg im Breisgau, , Germany

Hamburg, , Germany

Hanover, , Germany

München, , Germany

Haifa, , Israel

Jerusalem, , Israel

Petah Tikva, , Israel

Safed, , Israel

Tel Aviv, , Israel

Amsterdam-Zuidoost, , Netherlands

Leiden, , Netherlands

Nijmegen, , Netherlands

Bialystok, , Poland

Czeladź, , Poland

Kielce, , Poland

Lodz, , Poland

Warsaw, , Poland

Santurce, , Puerto Rico

Barcelona, , Spain

Madrid, , Spain

Seville, , Spain

Valencia, , Spain

Stockholm, , Sweden

Sankt Gallen, , Switzerland

Zurich, , Switzerland

Birmingham, , United Kingdom

London, , United Kingdom

Countries

United States; Australia; Austria; Belgium; Brazil; Canada; France; Germany; Israel; Netherlands; Poland; Puerto Rico; Spain; Sweden; Switzerland; United Kingdom

References

Zeuzem S, DeMasi R, Baldini A, Coate B, Luo D, Mrus J, Witek J. Risk factors predictive of anemia development during telaprevir plus peginterferon/ribavirin therapy in treatment-experienced patients. J Hepatol. 2014 Jun;60(6):1112-7. doi: 10.1016/j.jhep.2014.01.013. Epub 2014 Jan 29.

Reference Type: DERIVED

PMID: 24486089 (View on PubMed)

Younossi Z, Negro F, Serfaty L, Pol S, Diago M, Zeuzem S, Andreone P, Lawitz EJ, Roberts S, Focaccia R, Foster GR, Horban A, Lonjon-Domanec I, Coate B, DeMasi R, Picchio G, Witek J. Homeostasis model assessment of insulin resistance does not seem to predict response to telaprevir in chronic hepatitis C in the REALIZE trial. Hepatology. 2013 Dec;58(6):1897-906. doi: 10.1002/hep.26437. Epub 2013 Oct 17.

Reference Type: DERIVED

PMID: 24382638 (View on PubMed)

Pol S, Aerssens J, Zeuzem S, Andreone P, Lawitz EJ, Roberts S, Younossi Z, Foster GR, Focaccia R, Horban A, Pockros PJ, Van Heeswijk RP, De Meyer S, Luo D, Botfield M, Beumont M, Picchio G. Limited impact of IL28B genotype on response rates in telaprevir-treated patients with prior treatment failure. J Hepatol. 2013 May;58(5):883-9. doi: 10.1016/j.jhep.2012.12.023. Epub 2013 Jan 12.

Reference Type: DERIVED

PMID: 23321318 (View on PubMed)

Zeuzem S, Andreone P, Pol S, Lawitz E, Diago M, Roberts S, Focaccia R, Younossi Z, Foster GR, Horban A, Ferenci P, Nevens F, Mullhaupt B, Pockros P, Terg R, Shouval D, van Hoek B, Weiland O, Van Heeswijk R, De Meyer S, Luo D, Boogaerts G, Polo R, Picchio G, Beumont M; REALIZE Study Team. Telaprevir for retreatment of HCV infection. N Engl J Med. 2011 Jun 23;364(25):2417-28. doi: 10.1056/NEJMoa1013086.

Reference Type: DERIVED

PMID: 21696308 (View on PubMed)

Other Identifiers

VX-950-TIDP24-C216

Identifier Type: OTHER

Identifier Source: secondary_id

CR014842

Identifier Type: -

Identifier Source: org_study_id