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
Overview
- Phase
- Phase 3
- Intervention
- Telaprevir
- Conditions
- Hepatitis C, Chronic
- Sponsor
- Tibotec BVBA
- Enrollment
- 663
- Primary Endpoint
- Number of Participants With Sustained Virologic Response (SVR) 24 Weeks After the Last Planned Dose of Study Medication - SVR24 Planned
- Status
- Completed
- Last Updated
- 12 years ago
Overview
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.
Investigators
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
Arms & Interventions
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.
Intervention: Telaprevir
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.
Intervention: Peg-IFN-alfa-2a
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.
Intervention: Ribavirin
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.
Intervention: Placebo
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.
Intervention: Telaprevir
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.
Intervention: Peg-IFN-alfa-2a
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.
Intervention: Ribavirin
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.
Intervention: Placebo
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.
Intervention: Peg-IFN-alfa-2a
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.
Intervention: Ribavirin
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.
Intervention: Placebo
Outcomes
Primary Outcomes
Number of Participants With Sustained Virologic Response (SVR) 24 Weeks After the Last Planned Dose of Study Medication - SVR24 Planned
Time Frame: Week 72
SVR24 planned is defined as having undetectable plasma Hepatitis C virus (HCV) ribonucleic acid (RNA) levels 24 weeks after the last planned dose of study medication.
Secondary Outcomes
- Number of Participants With Sustained Virologic Response (SVR) 12 Weeks After the Last Planned Dose of Study Medication - SVR12 Planned(Week 60)
- Number of Participants Who Meet the Telaprevir Stopping Rule at Week 4, Week 6, or Week 8(Week 4, Week 6, or Week 8)
- Number of Participants Who Have Viral Relapse During Entire Follow-up Period (up to Week 72)(Up to Week 72)
- Change From Baseline in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Week 4(Baseline (Day 1) to Week 4)
- Number of Participants Acheiving Extended Rapid Virologic Response at Week 4 and Week 12(Week 4 and Week 12)
- Number of Participants Acheiving Rapid Virologic Response (RVR) at Week 4(Week 4)
- Number of Participants Acheiving Undetectable Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels at Week 48 (End of Treatment)(Week 48)