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

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase IIa Randomized, Open-Label Study of Telaprevir (VX-950) Administered Every 12 or Every 8 Hours in Combination With Either Peg-IFN alfa2a (Pegasys) and Ribavirin (Copegus) or Peg-IFN alfa2b (PegIntron) and Ribavirin (Rebetol) in Treatment-Naive Subjects With Chronic Genotype 1 Hepatitis C Infection

Conditions
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Chronic Hepatitis C

Intervention / Treatment
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* Drug: Telaprevir
* Drug: Peg-IFN-alfa-2a
* Drug: Peg-IFN-alfa-2b
* Drug: Ribavirin (RBV) tablet
* Drug: Ribavirin (RBV) capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Telaprevir 750 mg with Peg-IFN-alfa-2a/RBV tablet<br>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. | Drug: Telaprevir<br>* Oval tablets containing 375 mg of telaprevir for oral administration.<br>Drug: Peg-IFN-alfa-2a<br>* Solution containing Peg-IFN alfa2a for subcutaneous injection in a pre-filled syringe.<br>Drug: Ribavirin (RBV) tablet<br>* Tablets containing 200 mg RBV for oral administration.<br>|
| Experimental: Telaprevir 750 mg with Peg-IFN-alfa-2b/RBV capsule<br>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. | Drug: Telaprevir<br>* Oval tablets containing 375 mg of telaprevir for oral administration.<br>Drug: Peg-IFN-alfa-2b<br>* Powder containing Peg-IFN-alfa-2b and solvent for solution for subcutaneous injection in a pre-filled pen.<br>Drug: Ribavirin (RBV) capsule<br>* Capsules containing 200 mg RBV for oral administration.<br>|
| Experimental: Telaprevir 1125 mg with Peg-IFN-alfa-2a/RBV tablet<br>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. | Drug: Telaprevir<br>* Oval tablets containing 375 mg of telaprevir for oral administration.<br>Drug: Peg-IFN-alfa-2a<br>* Solution containing Peg-IFN alfa2a for subcutaneous injection in a pre-filled syringe.<br>Drug: Ribavirin (RBV) tablet<br>* Tablets containing 200 mg RBV for oral administration.<br>|
| Experimental: Telaprevir 1125 mg with Peg-IFN-alfa-2b/RBV capsule<br>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. | Drug: Telaprevir<br>* Oval tablets containing 375 mg of telaprevir for oral administration.<br>Drug: Peg-IFN-alfa-2b<br>* Powder containing Peg-IFN-alfa-2b and solvent for solution for subcutaneous injection in a pre-filled pen.<br>Drug: Ribavirin (RBV) capsule<br>* Capsules containing 200 mg RBV for oral administration.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Virologic Response at Week 12 | 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). | End of treatment (EOT) (up to Week 48) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to First Undetectable Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Level | 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). | Baseline (Day 1) up to EOT (up to Week 48) | 
| Number of Participants With Viral Breakthrough at End of Treatment (EOT) | 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. | EOT (up to Week 48) | 
| Percentage of Participants With Partial Response | 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). | Baseline (Day 1) up to EOT (up to Week 48) | 
| Change From Baseline in Log 10-Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Values at 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. | Baseline (pre-dose), Week 12 | 
| Change From Baseline in Log 10-Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Values at End of Treatment (EOT) | 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. | Baseline (pre-dose), EOT (up to Week 48) | 
| Percentage of Participants With Sustained Viral Response 24 Weeks After End of Treatment (SVR24) | 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. | EOT (up to Week 48) and up to 24 weeks after EOT | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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VX-950-TiDP24-C208, Chronic Hepatitis C, Genotype 1, Telaprevir, Treatment-naïve, VX-950-C208