An Open-Label Study of Telaprevir Administered Every 12 or 8 Hours in Combination With One of Two Pegylated Interferons and Ribavirin in Treatment-Naive Genotype 1 Chronic Hepatitis C Participants
- Conditions
- Chronic Hepatitis C
- Interventions
- Drug: Peg-IFN-alfa-2aDrug: Peg-IFN-alfa-2b
- Registration Number
- NCT00528528
- Lead Sponsor
- Tibotec BVBA
- Brief Summary
The purpose of this study is to explore the efficacy, safety, tolerability, pharmacokinetics (the study of the way a drug enters and leaves the blood and tissues over time), and pharmacokinetic-pharmacodynamic relationships of telaprevir administered in two different doses in combination with two standard therapies commercially available for chronic (lasting a long time) genotype 1 Hepatitis (inflammation of the liver) C virus (HCV) infection.
- Detailed Description
This is a Phase 2a, open-label (all people know the identity of the intervention), multicenter trial (conducted in more than one center) in participants with chronic genotype 1 HCV infection. The trial consists of a Screening phase of approximately 4 weeks, a treatment phase up to 48 weeks depending on participants' individual virologic response, and a follow-up phase of at least 24 weeks. All participants will receive 12 weeks of telaprevir treatment in combination with standard therapy. At Week 12, telaprevir dosing will end and participants will continue on standard therapy only. Participants will be randomly assigned to receive one of the two different dosage regimens of telaprevir (750 milligram \[mg\] every 8 hours (hr), or 1125 mg every 12 hr) in combination with standard therapy (pegylated interferon \[Peg-IFN\]-alfa-2a and ribavirin \[RBV\] or Peg-IFN-alfa-2b and RBV at the standard doses). Efficacy will be evaluated by HCV Ribonucleic Acid (RNA) values, viral response, viral breakthrough, partial response, early viral kinetics and sustained viral response. Pharmacokinetics, Pharmacokinetic-pharmacodynamic relationship will also be evaluated. Safety will be monitored throughout the study duration.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 166
- Chronic genotype 1 Hepatitis (inflammation of the liver) C infection
- Never been treated for Hepatitis C Viral (HCV) infection
- No clinically significant lab abnormalities
- Amount of HCV Ribonucleic acid (RNA) in the blood more than 10,000 international units/milliliter (IU/mL) at entry
- Liver biopsy or "Fibroscan" test performed during screening or in the past 3 years
- Contra-indications for starting anti-HCV therapy
- History or evidence of liver cirrhosis (serious liver disorder in which connective tissue replaces normal liver tissue, and liver failure often occurs) or decompensated liver disease
- Any evidence of significant liver disease in addition to Hepatitis C
- Infected with Human Immunodeficiency Virus (a life-threatening infection which you can get from an infected person's blood or from having sex with an infected person) or Hepatitis B
- Women who are pregnant (carrying an unborn baby), planning to be pregnant or breastfeeding or the partner of a woman who is pregnant or breastfeeding
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Telaprevir 1125 mg with Peg-IFN-alfa-2a/RBV tablet Peg-IFN-alfa-2a Telaprevir tablets at the dose of 1125 mg orally administered every 12 hr for 12 weeks, in combination with standard treatment composed of Peg-IFN-alfa-2a solution for subcutaneous injection at the dose of 180 mcg/week and RBV oral tablets at the dose of 1000-1200 mg/day up to 48 weeks. Telaprevir 1125 mg with Peg-IFN-alfa-2b/RBV capsule Peg-IFN-alfa-2b Telaprevir tablets at the dose of 1125 mg orally administered every 12 hr for 12 weeks, in combination with standard treatment composed of Peg-IFN-alfa-2b solution for subcutaneous injection at the dose of 1.5 mcg/kg/week and RBV oral capsules at the dose of 800-1200 mg/day up to 48 weeks. Telaprevir 750 mg with Peg-IFN-alfa-2a/RBV tablet Ribavirin (RBV) tablet Telaprevir tablets at the dose of 750 milligram (mg) orally administered every 8 hours (hr) for 12 weeks, in combination with standard treatment composed of pegylated interferon (Peg-IFN)-alfa-2a solution for subcutaneous injection at the dose of 180 microgram per week (mcg/week) and ribavirin (RBV) oral tablets at the dose of 1000-1200 mg/day up to 48 weeks. Telaprevir 750 mg with Peg-IFN-alfa-2a/RBV tablet Telaprevir Telaprevir tablets at the dose of 750 milligram (mg) orally administered every 8 hours (hr) for 12 weeks, in combination with standard treatment composed of pegylated interferon (Peg-IFN)-alfa-2a solution for subcutaneous injection at the dose of 180 microgram per week (mcg/week) and ribavirin (RBV) oral tablets at the dose of 1000-1200 mg/day up to 48 weeks. Telaprevir 750 mg with Peg-IFN-alfa-2a/RBV tablet Peg-IFN-alfa-2a Telaprevir tablets at the dose of 750 milligram (mg) orally administered every 8 hours (hr) for 12 weeks, in combination with standard treatment composed of pegylated interferon (Peg-IFN)-alfa-2a solution for subcutaneous injection at the dose of 180 microgram per week (mcg/week) and ribavirin (RBV) oral tablets at the dose of 1000-1200 mg/day up to 48 weeks. Telaprevir 750 mg with Peg-IFN-alfa-2b/RBV capsule Telaprevir Telaprevir tablets at the dose of 750 mg orally administered every 8 hr for 12 weeks, in combination with standard treatment composed of Peg-IFN-alfa-2b solution for subcutaneous injection at the dose of 1.5 mcg/kilogram/week (mcg/kg/week) and RBV oral capsules at the dose of 800-1200 mg/day up to 48 weeks. Telaprevir 750 mg with Peg-IFN-alfa-2b/RBV capsule Ribavirin (RBV) capsule Telaprevir tablets at the dose of 750 mg orally administered every 8 hr for 12 weeks, in combination with standard treatment composed of Peg-IFN-alfa-2b solution for subcutaneous injection at the dose of 1.5 mcg/kilogram/week (mcg/kg/week) and RBV oral capsules at the dose of 800-1200 mg/day up to 48 weeks. Telaprevir 750 mg with Peg-IFN-alfa-2b/RBV capsule Peg-IFN-alfa-2b Telaprevir tablets at the dose of 750 mg orally administered every 8 hr for 12 weeks, in combination with standard treatment composed of Peg-IFN-alfa-2b solution for subcutaneous injection at the dose of 1.5 mcg/kilogram/week (mcg/kg/week) and RBV oral capsules at the dose of 800-1200 mg/day up to 48 weeks. Telaprevir 1125 mg with Peg-IFN-alfa-2a/RBV tablet Telaprevir Telaprevir tablets at the dose of 1125 mg orally administered every 12 hr for 12 weeks, in combination with standard treatment composed of Peg-IFN-alfa-2a solution for subcutaneous injection at the dose of 180 mcg/week and RBV oral tablets at the dose of 1000-1200 mg/day up to 48 weeks. Telaprevir 1125 mg with Peg-IFN-alfa-2a/RBV tablet Ribavirin (RBV) tablet Telaprevir tablets at the dose of 1125 mg orally administered every 12 hr for 12 weeks, in combination with standard treatment composed of Peg-IFN-alfa-2a solution for subcutaneous injection at the dose of 180 mcg/week and RBV oral tablets at the dose of 1000-1200 mg/day up to 48 weeks. Telaprevir 1125 mg with Peg-IFN-alfa-2b/RBV capsule Telaprevir Telaprevir tablets at the dose of 1125 mg orally administered every 12 hr for 12 weeks, in combination with standard treatment composed of Peg-IFN-alfa-2b solution for subcutaneous injection at the dose of 1.5 mcg/kg/week and RBV oral capsules at the dose of 800-1200 mg/day up to 48 weeks. Telaprevir 1125 mg with Peg-IFN-alfa-2b/RBV capsule Ribavirin (RBV) capsule Telaprevir tablets at the dose of 1125 mg orally administered every 12 hr for 12 weeks, in combination with standard treatment composed of Peg-IFN-alfa-2b solution for subcutaneous injection at the dose of 1.5 mcg/kg/week and RBV oral capsules at the dose of 800-1200 mg/day up to 48 weeks.
- Primary Outcome Measures
Name Time Method Percentage of Participants With Virologic Response at Week 12 End of treatment (EOT) (up to Week 48) Virologic response was either defined as having undetectable Hepatitis C Virus (HCV) ribonucleic acid (RNA) (i.e., no HCV RNA was detected in the participants' plasma samples) or less than 25 international units/milliliter (IU/mL) HCV RNA (i.e., the participants' plasma samples contained traces of HCV RNA at a concentration below the limit of quantification of the viral load assay or no HCV RNA was detected in the samples).
- Secondary Outcome Measures
Name Time Method Time to First Undetectable Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Level Baseline (Day 1) up to EOT (up to Week 48) Virologic response was either defined as having undetectable HCV RNA (i.e., no HCV RNA was detected in the participants' plasma samples) or less than 25 IU/mL HCV RNA (i.e., the participants' plasma samples contained traces of HCV RNA at a concentration below the limit of quantification of the viral load assay or no HCV RNA was detected in the samples).
Number of Participants With Viral Breakthrough at End of Treatment (EOT) EOT (up to Week 48) Viral breakthrough was defined as a confirmed increase of more than 1 log 10 in HCV RNA level from the lowest level reached or a confirmed value of HCV RNA more than 100 IU/mL in participants whose HCV RNA was previously less than 25 IU/mL.
Change From Baseline in Log 10-Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Values at End of Treatment (EOT) Baseline (pre-dose), EOT (up to Week 48) Change from baseline in log 10 of Plasma HCV RNA levels were measured using the COBAS TaqMan HCV test (lower limit of quantification 25 IU/mL). The assay used real-time reverse transcription - polymerase chain reaction (RT-PCR) methodology.
Change From Baseline in Log 10-Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Values at Week 12 Baseline (pre-dose), Week 12 Change from baseline in log 10 of Plasma HCV RNA levels were measured using the COBAS TaqMan HCV test (lower limit of quantification 25 IU/mL). The assay used real-time reverse transcription - polymerase chain reaction (RT-PCR) methodology. HCV RNA samples were taken pre-dose of Peg-IFN administration.
Percentage of Participants With Sustained Viral Response 24 Weeks After End of Treatment (SVR24) EOT (up to Week 48) and up to 24 weeks after EOT SVR24 was defined as having undetectable HCV RNA (i.e., no HCV RNA is detected in the participants' plasma samples) at EOT and no confirmed detectable HCV RNA levels between EOT and 24 weeks after the last dose of study medication.
Percentage of Participants With Partial Response Baseline (Day 1) up to EOT (up to Week 48) Partial response was defined as having at least 2 log drop in HCV RNA from Baseline, but not having undetectable HCV RNA (i.e., no HCV RNA is detected in the participants' plasma samples).