Clinical trial NCT00703118: A Safety and Effectiveness Study of Telaprevir in Chronic, Genotype 1, Hepatitis C Patients That Failed Previous Standard Treatment
Official title: A Randomized, Double-Blind, Placebo-Controlled, Phase III Trial of 2 Regimens of Telaprevir (With and Without Delayed Start) Combined With Pegylated Interferon Alfa-2a (Pegasys) and Ribavirin (Copegus) in Subjects With Chronic, Genotype 1, Hepatitis C Infection Who Failed Prior Standard Treatment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hepatitis C, Chronic
Keywords: Hepatitis C, Chronic
Telaprevir
Peg-IFN-alfa-2a
Ribavirin
Lead sponsor: Tibotec BVBA
Sponsor class: INDUSTRY
Collaborators: name: Tibotec Pharmaceutical Limited
First posted: 2008-06-23
Enrollment: 663
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 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.

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

Primary outcomes:
measure: Number of Participants With Sustained Virologic Response (SVR) 24 Weeks After the Last Planned Dose of Study Medication - SVR24 Planned
timeFrame: Week 72
Secondary outcomes:
measure: Number of Participants Acheiving Rapid Virologic Response (RVR) at Week 4
timeFrame: Week 4
measure: Number of Participants Acheiving Undetectable Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels at Week 48 (End of Treatment)
timeFrame: Week 48
measure: Number of Participants With Sustained Virologic Response (SVR) 12 Weeks After the Last Planned Dose of Study Medication - SVR12 Planned
timeFrame: Week 60
measure: Number of Participants Who Meet the Telaprevir Stopping Rule at Week 4, Week 6, or Week 8
timeFrame: Week 4, Week 6, or Week 8
measure: Number of Participants Who Have Viral Relapse During Entire Follow-up Period (up to Week 72)
timeFrame: Up to Week 72
measure: Change From Baseline in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Week 4
timeFrame: Baseline (Day 1) to Week 4
measure: Number of Participants Acheiving Extended Rapid Virologic Response at Week 4 and Week 12
timeFrame: Week 4 and Week 12
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Coronado
country: United States
state: California
city: La Jolla
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: San Francisco
country: United States
state: California
city: Aurora
country: United States
state: Colorado
city: Bradenton
country: United States
state: Florida
city: Gainesville
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Indianapolis
country: United States
state: Indiana
city: Baltimore
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: Worcester
country: United States
state: Massachusetts
city: Detroit
country: United States
state: Michigan
city: Plymouth
country: United States
state: Minnesota
city: Kansas City
country: United States
state: Missouri
city: Egg Harbor Twp
country: United States
state: New Jersey
city: Albuquerque
country: United States
state: New Mexico
city: Manhasset
country: United States
state: New York
city: New York
country: United States
state: New York
city: Chapel Hill
country: United States
state: North Carolina
city: Durham
country: United States
state: North Carolina
city: Philadelphia
country: United States
state: Pennsylvania
city: Columbia
country: United States
state: South Carolina
city: Dallas
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Falls Church
country: United States
state: Virginia
city: Norfolk
country: United States
state: Virginia
city: Richmond
country: United States
state: Virginia
city: Adelaide
country: Australia
city: Camperdown
country: Australia
city: Clayton
country: Australia
city: Darlinghurst
country: Australia
city: Kingswood
country: Australia
city: Melbourne
country: Australia
city: Parkville - Vic
country: Australia
city: Perth
country: Australia
city: Graz N/A
country: Austria
city: Wien
country: Austria
city: Brussels
country: Belgium
city: Bruxelles
country: Belgium
city: Gent
country: Belgium
city: Leuven
country: Belgium
city: Distrito Barao Geraldo-Campina
country: Brazil
city: Salvador
country: Brazil
city: Santo Andre
country: Brazil
city: Sao Paulo
country: Brazil
city: Vancouver
country: Canada
state: British Columbia
city: Ottawa
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Clichy
country: France
city: Creteil N/A
country: France
city: Grenoble
country: France
city: Lille Cedex
country: France
city: Lyon Cedex 02
country: France
city: Lyon
country: France
city: Marseille
country: France
city: Paris
country: France
city: Pessac
country: France
city: Vandoeuvre Les Nancy
country: France
city: Berlin
country: Germany
city: Düsseldorf
country: Germany
city: Frankfurt N/A
country: Germany
city: Freiburg
country: Germany
city: Hamburg
country: Germany
city: Hannover
country: Germany
city: Koln
country: Germany
city: München
country: Germany
city: Haifa
country: Israel
city: Jerusalem
country: Israel
city: Petah Tiqva
country: Israel
city: Tel-Aviv
country: Israel
city: Zefat
country: Israel
city: Amsterdam Zuidoost
country: Netherlands
city: Leiden
country: Netherlands
city: Nijmegen
country: Netherlands
city: Bialystok
country: Poland
city: Czeladz
country: Poland
city: Kielce
country: Poland
city: Lodz
country: Poland
city: Warszawa
country: Poland
city: Santurce
country: Puerto Rico
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Sevilla N/A
country: Spain
city: Valencia
country: Spain
city: Stockholm
country: Sweden
city: St Gallen
country: Switzerland
city: Zurich N/A
country: Switzerland
city: Birmingham
country: United Kingdom
city: London
country: United Kingdom
Study officials:
affiliation: Tibotec BVBA
name: Tibotec-Virco Virology BVBA Clinical Trial
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.