A Dose Ranging Study Of PF-00868554 In Combination With PEGASYS And COPEGUS In Patients With Chronic Hepatitis C Genotype 1 Infection

Study Overview
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Brief Summary
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The purpose of this study is to further assess the potency of PF-00868554, an HCV polymerase inhibitor, in subjects chronically infected with HCV by evaluating the antiviral activity of PF-00868554 in combination with current standard of care therapy, pegylated interferon-alpha2a (PEGASYS) and ribavirin (COPEGUS).

Official Title
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A Phase 2, Randomized, Placebo Controlled, Dose Ranging Study To Evaluate Peginterferon Alfa 2a (Pegasys®) And Ribavirin (Copegus®) With And Without PF-00868554 In Subjects Chronically Infected With Hepatitis C Virus

Conditions
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Hepatitis C

Intervention / Treatment
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* Drug: PF-00868554
* Drug: PF-00868554
* Drug: PF-00868554
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Treatment naive (no prior treatment with IFN-a +/- RBV regimens. Subjects who have discontinued IFN-a containing regimens after <2 weeks of therapy due to tolerability issues are considered treatment naive. HCV RNA > 100,000 IU/mL at screening. Genotype 1. A diagnosis of chronic HCV infection for at least 6 months. Exclusion Criteria: Evidence of acute or chronic infection with HIV or HBV. Exposure within the previous three months to an investigational anti-HCV agent. Evidence of severe or decompensated liver disease. Subjects with liver disease unrelated to HCV infection.

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>500 mg BID | Drug: PF-00868554<br>* 500 mg BID administered as 5x100 mg tablets for 4 weeks in combination with standard of care; standard of care continued for an additional 44 weeks.<br>|
| Experimental: B<br>300 mg BID | Drug: PF-00868554<br>* 300 mg BID administered as 3x100 mg tablets for 4 weeks in combination with standard of care; standard of care continued for an additional 44 weeks<br>|
| Experimental: C<br>200 mg BID | Drug: PF-00868554<br>* 200 mg BID administered as 2x100 mg tablets for 4 weeks in combination with standard of care; standard of care continued for an additional 44 weeks<br>|
| Placebo Comparator: D<br>Placebo | Drug: Placebo<br>* Placebo administered for 4 weeks in combination with standard of care; standard of care continued for an additional 44 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Week 4 - Full Analysis Set | Plasma HCV RNA levels were measured using the Roche COBAS Taqman assay (limit of detection: 25 international unit per milliliter [IU/mL]). Baseline value calculated as the average of the screening and Day 1 pre-dose measurements. | Baseline, Week 4 | 
| Change From Baseline in Plasma Log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Week 4 - Modified Analysis Set | Plasma HCV RNA levels were measured using the Roche COBAS Taqman assay (limit of detection: 25 IU/mL). Baseline value calculated as the average of the screening and Day 1 pre-dose measurements. | Baseline, Week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Participants Achieving Undetectable Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) | Proportion of participants achieving undetectable plasma HCV RNA at Week 4 (rapid virologic response), at Week 12 (early virologic response), at Week 48 (end of treatment response), at Week 60 (sustained virologic response; 12 weeks after cessation of therapy), at Week 72 (sustained virologic response; 24 weeks after cessation of therapy) were summarized. Undetectable viral load was defined as HCV RNA <25 IU/mL. | Week 4, 12, 48, 60, 72 | 
| Alanine Aminotransferase (ALT) Levels |  | Week 4, 12, 48, 72 | 
| Population Pharmacokinetics (PK) of PF-00868554 | Data for this Outcome Measure are not reported here because the analysis population includes participants who were not enrolled in this study. ClinicalTrials.gov is designed for reporting results from only those participants who were enrolled in the study and described in the Participant Flow and Baseline Characteristics modules. | 1, 2 and 6 hours post-dose on Day 1; 0 hour (pre-dose) on Day 7, 14, 21; 0 hour (pre-dose), 2, 6 hours post-dose on Day 28 |