A Study of Mericitabine in Combination With Telaprevir and Peginterferon Alfa-2a / Ribavirin in Participants With Chronic Hepatitis C

Study Overview
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Brief Summary
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This randomized, double-blind, multi-center, parallel-group study will evaluate the sustained virologic response and the safety of mericitabine (RO5024048) (MCB) in combination with telaprevir (TVR) and peginterferon Alfa-2a (PEG-IFN) / ribavirin (RBV) in participants with chronic Hepatitis C infection.

Official Title
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A Phase II, Randomized, Double-Blind, Multicenter, Parallel Group Study to Evaluate the Sustained Virologic Response of the HCV Polymerase Inhibitor Prodrug RO5024048 in Combination With Telaprevir and Pegasys®/Copegus® in Patients With Chronic Hepatitis C Genotype 1 Virus Infection Who Were Prior Null Responders to Treatment With Pegylated Interferon/Ribavirin

Conditions
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Hepatitis C

Intervention / Treatment
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* Drug: Ribavirin
* Drug: Mericitabine
* Drug: Peginterferon Alfa-2a
* Drug: Placebo
* Drug: Telaprevir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chronic hepatitis C infection for at least 6 months duration Hepatitis C genotype 1a or 1b Participants must have discontinued prior hepatitis C treatment at least 12 weeks prior to enrollment in this study Participants showed a previous null response to therapy as defined by < 2 logarithm to the base 10 (log10) international units per milliliter (IU/mL) decrease in viral titer after at least 12 weeks of treatment with PEG-IFN/RBV Exclusion Criteria: Hepatitis C infection with a genotype other than genotype 1a or 1b Body mass index < 18 or >= 36 kilograms per square meters (kg/m^2) Hepatitis A, hepatitis B, or human immunodeficiency virus (HIV) infection Herbal remedies <=1 month prior to the first dose of study drug

Ages Eligible for Study
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Minimum Age: 18 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TVR (12 Weeks), MCB (24 Weeks), PEG-IFN/RBV (24 Weeks)<br>Twelve weeks of therapy with MCB, TVR, and PEG-IFN/RBV, followed by 12 weeks of therapy with MCB and PEG-IFN/RBV (total treatment duration of 24 weeks). | Drug: Ribavirin<br>* Participants will receive a total daily dose of 1000 milligrams (mg) (for participants weighing less than [<] 75 kg) or 1200 mg (for participants weighing greater than or equal to [>=] 75 kg) orally for 24 or 48 weeks.<br>* Other names: Copegus;Drug: Mericitabine<br>* Participants will receive mericitabine 1000 mg orally twice daily.<br>Drug: Peginterferon Alfa-2a<br>* Participants will receive 180 micrograms (mcg) subcutaneous injection once weekly.<br>* Other names: Pegasys;Drug: Telaprevir<br>* Participants will receive telaprevir 750 mg orally three times daily.<br>|
| Experimental: TVR (12 Weeks), MCB (24 Weeks), PEG-IFN/RBV (48 Weeks)<br>Twelve weeks of therapy with MCB, TVR, and PEG-IFN/RBV, followed by 12 weeks of therapy with MCB and PEG-IFN/RBV and then 12 weeks of therapy with PEG-IFN/RBV (total treatment duration of 48 weeks). | Drug: Ribavirin<br>* Participants will receive a total daily dose of 1000 milligrams (mg) (for participants weighing less than [<] 75 kg) or 1200 mg (for participants weighing greater than or equal to [>=] 75 kg) orally for 24 or 48 weeks.<br>* Other names: Copegus;Drug: Mericitabine<br>* Participants will receive mericitabine 1000 mg orally twice daily.<br>Drug: Peginterferon Alfa-2a<br>* Participants will receive 180 micrograms (mcg) subcutaneous injection once weekly.<br>* Other names: Pegasys;Drug: Telaprevir<br>* Participants will receive telaprevir 750 mg orally three times daily.<br>|
| Experimental: TVR, MCB, Placebo MCB( each for 12Weeks),PEG-IFN/RBV(48 Weeks)<br>Twelve weeks of therapy with MCB, TVR, and PEG-IFN/RBV, followed by 12 weeks of therapy with placebo matching to MCB and PEG-IFN/RBV, and then 24 weeks of therapy with PEG-IFN/RBV (total treatment duration of 48 weeks). | Drug: Ribavirin<br>* Participants will receive a total daily dose of 1000 milligrams (mg) (for participants weighing less than [<] 75 kg) or 1200 mg (for participants weighing greater than or equal to [>=] 75 kg) orally for 24 or 48 weeks.<br>* Other names: Copegus;Drug: Mericitabine<br>* Participants will receive mericitabine 1000 mg orally twice daily.<br>Drug: Peginterferon Alfa-2a<br>* Participants will receive 180 micrograms (mcg) subcutaneous injection once weekly.<br>* Other names: Pegasys;Drug: Placebo<br>* Participants will receive placebo matching to mericitabine orally twice daily.<br>Drug: Telaprevir<br>* Participants will receive telaprevir 750 mg orally three times daily.<br>|
| Active Comparator: TVR(12 Weeks), Placebo MCB (24 Weeks), PEG-IFN/RBV(48 Weeks)<br>Twelve weeks of therapy with placebo matching to MCB, TVR, PEG-IFN/RBV, will be followed by 12 weeks of therapy with placebo matching to MCB along with PEG-IFN/RBV , following 24 weeks of therapy with PEG-IFN/RBV (total treatment duration of 48 weeks). | Drug: Ribavirin<br>* Participants will receive a total daily dose of 1000 milligrams (mg) (for participants weighing less than [<] 75 kg) or 1200 mg (for participants weighing greater than or equal to [>=] 75 kg) orally for 24 or 48 weeks.<br>* Other names: Copegus;Drug: Peginterferon Alfa-2a<br>* Participants will receive 180 micrograms (mcg) subcutaneous injection once weekly.<br>* Other names: Pegasys;Drug: Placebo<br>* Participants will receive placebo matching to mericitabine orally twice daily.<br>Drug: Telaprevir<br>* Participants will receive telaprevir 750 mg orally three times daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of Participants With Sustained Virological Response 12 Weeks After End of Treatment (SVR12), as Determined by Polymerase Chain Reaction (PCR) Using Roche COBAS TaqMan Hepatitis C Virus (HCV) Test |  | 12 weeks after end of treatment (up to Week 60) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Sustained Virological Response 4 Weeks After End of Treatment (SVR-4), as Determined by PCR Using Roche COBAS TaqMan HCV Test |  | 4 weeks after end of treatment (up to Week 52) | 
| Percentage of Participants With Sustained Virological Response 24 Weeks After End of Treatment (SVR-24), as Determined by PCR Using Roche COBAS TaqMan HCV Test |  | 24 weeks after end of treatment (up to Week 72) | 
| Percentage of Participants With Virological Response Over Time From Week 2 to Week 48, as Determined by PCR Using Roche COBAS TaqMan HCV Test |  | Weeks 2, 4, 12, 24, and 48 | 
| Percentage of Participants With Treatment- Resistant Mutations, as Determined Using Standard Sequencing Technology |  | Baseline up to Week 60 | 
| Change From Baseline in HCV Ribonucleic Acid (RNA) Levels |  | Baseline, Weeks 1, 2, 4, 8, 12, 16, 20, 24, 30, 36, 42, 48, 52, 60, and 72 | 
| Percentage of Participants With Adverse Event |  | Baseline up to Week 72 | 
| Trough Concentration of RO4995855 (Parent Drug of Mericitabine) |  | Pre-dose (-0.5 hour) on Day 1 and Week 8; 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 12 hour post dose in Week 8 | 
| Trough Concentration of Metabolite of RO4995855 (RO5012433) |  | Pre-dose (-0.5 hour) on Day 1 and Week 8; 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 12 hour post dose in Week 8 | 
| Trough Concentration of Telaprevir |  | Pre-dose (-0.5 hour) on Day 1 and Week 8; 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 12 hour post dose in Week 8 |