A Study of Mericitabine in Combination With Boceprevir and Pegasys/Copegus in Patients With Chronic Hepatitis C

Study Overview
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Brief Summary
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This randomized, double-blind, multi-center, placebo-controlled, parallel-group study will evaluate the sustained virologic response and the safety of mericitabine (RO5024048) in combination with boceprevir and Pegasys/Copegus in patients with chronic hepatitis C infection. The anticipated time on study treatment is up to 48 weeks.

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 Boceprevir 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, Chronic

Intervention / Treatment
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* Drug: Copegus
* Drug: Copegus
* Drug: Pegasys
* Drug: Pegasys
* Drug: boceprevir
* Drug: boceprevir
* Drug: mericitabine
* Drug: mericitabine placebo
* Drug: boceprevir placebo
* Drug: boceprevir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients, >/=18 years of age Chronic hepatitis C infection for at least 6 months duration Hepatitis C genotype 1a or 1b Patients must have discontinued prior hepatitis C treatment at least 12 weeks prior to enrollment in this study Patient showed a previous null response to therapy as defined by < 2 log10 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 Hepatitis A, hepatitis B, or 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: Treatment Arm A<br>24 weeks of therapy with mericitabine 1000 mg twice a day (BID), boceprevir 800 mg three times daily (TID), Pegasys 180 microgram/week, and Copegus 1000/1200 mg/day (total treatment duration of 24 weeks), followed by a 24-week treatment-free follow-up period. | Drug: Copegus<br>* total daily dose of 1000 mg or 1200 mg for 24 weeks<br>Drug: Pegasys<br>* 180 microgram subcutaneous once a week for 24 weeks<br>Drug: boceprevir<br>* 800 mg three times a day for 24 weeks<br>Drug: mericitabine<br>* 1000 mg twice daily for 24 weeks<br>|
| Experimental: Treatment Arm B<br>24 weeks of therapy with mericitabine + boceprevir + Pegasys/Copegus followed by 24 weeks of therapy with boceprevir + Pegasys/Copegus (triple) (total treatment duration of 48 weeks), followed by a 24-week treatment-free follow-up period. | Drug: Copegus<br>* total daily dose of 1000 mg or 1200 mg for 48 weeks<br>Drug: Pegasys<br>* 180 microgram subcutaneous once a week for 48 weeks<br>Drug: boceprevir<br>* 800 mg three times a day for 48 weeks<br>Drug: mericitabine<br>* 1000 mg twice daily for 24 weeks<br>|
| Active Comparator: Treatment Arm C (Control)<br>4 weeks of therapy with mericitabine placebo, boceprevir placebo + Pegasys/Copegus, then 20 weeks of therapy with mericitabine placebo + boceprevir + Pegasys/Copegus, then 24 weeks of therapy with boceprevir + Pegasys/Copegus (total treatment duration of 48 weeks), followed by a 24-week treatment-free follow-up period. | Drug: Copegus<br>* total daily dose of 1000 mg or 1200 mg for 48 weeks<br>Drug: Pegasys<br>* 180 microgram subcutaneous once a week for 48 weeks<br>Drug: mericitabine placebo<br>* mericitabine placebo<br>Drug: boceprevir placebo<br>* boceprevir placebo<br>Drug: boceprevir<br>* 800 mg three times a day for 44 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sustained virological response 12 weeks after treatment (SVR-12) |  | up to 60 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sustained virological response 4 weeks after treatment |  | up to 52 weeks | 
| Virologic response over time |  | 60 weeks | 
| Proportion of patients who develop treatment resistance |  | 60 weeks | 
| Safety (incidence of adverse events) |  | 60 weeks | 
| Pharmacokinetics: trough concentration of RO4995855 |  | Day 1 and Week 8 | 
| Pharmacokinetics: trough concentration of RO5012433 |  | Day 1 and Week 8 | 
| Pharmacokinetics: trough concentration of boceprevir |  | Day 1 and Week 8 |