Boceprevir/Peginterferon/Ribavirin for Chronic Hepatitis C: Erythropoietin Use Versus Ribavirin Dose Reduction for Anemia (P06086 AM2)

Study Overview
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Brief Summary
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The current trial is designed to prospectively explore the safety of erythropoietin use for the treatment of anemia during boceprevir plus peginterferon alfa-2b/Ribavirin (PEG2b/RBV) therapy and to assess its relationship to efficacy. All participants in this trial will be treated with the triple combination of boceprevir plus PEG2b/RBV. If a participant becomes anemic during treatment, the participant will be randomized to one of two therapeutic strategies for management of anemia (erythropoietin use versus RBV dose reduction).

Official Title
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Boceprevir and Peginterferon/Ribavirin for the Treatment of Chronic Hepatitis C in Treatment-Naive Subjects: A Comparison of Erythropoietin Use Versus Ribavirin Dose Reduction for the Management of Anemia

Conditions
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Hepatitis C, Chronic

Intervention / Treatment
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* Drug: Boceprevir
* Drug: Peginterferon alfa-2b (PEG2b)
* Drug: Ribavirin (RBV)
* Drug: Erythropoietin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant must have previously documented Chronic Hepatitis C (CHC) genotype 1 infection. Hemoglobin concentration at Screening must be ≤15 g/dL for both females and males. Participant must have a liver biopsy with histology consistent with CHC and no other etiology. Participant with bridging fibrosis (F3) or cirrhosis (F4) must have an ultrasound within 6 months of the Screening Visit (or between Screening and Day 1) with no findings suspicious for hepatocellular carcinoma. Participant's weight must be ≥40 kg and ≤125 kg. Participant and participant's partner(s) must each agree to use acceptable methods of contraception for at least 2 weeks prior to Day 1 and continue until at least 6 months after last dose of study medication, or longer if dictated by local regulations. Participant must be willing to give written informed consent. Participant must be willing to attend frequent site visits for the duration of the trial. Participant must not have any contraindications for the use of erythropoietin. Exclusion Criteria: Participants known to be coinfected with the human immunodeficiency virus (HIV) or hepatitis B virus. Participants who received prior treatment for hepatitis C. Treatment with any investigational drug within 30 days of the screening visit in this trial. Participants receiving any of the following medication(s) within 2 weeks prior to the Day 1 visit: alfuzosin, antiarrhythmics (amiodarone, bepridil, flecainide, propafenone, and quinidine), ergot derivatives, cisapride, lovastatin, simvastatin, pimozide, triazolam, and orally administered midazolam. Participation in any other clinical trial within 30 days of the screening visit in this trial or intention to participate in another clinical trial during participation in this trial. Evidence of decompensated liver disease. Diabetic and/or hypertensive participants with clinically significant ocular examination findings. Pre-existing psychiatric condition(s). Clinical diagnosis of substance abuse of specified drugs within specified timeframes. Any known pre-existing medical condition that could interfere with the participant's participation in and completion of the trial. Evidence of active or suspected malignancy, or a history of malignancy, within the last 5 years (except adequately treated carcinoma in situ and basal cell carcinoma of the skin). Participants who are pregnant or nursing. Participants who intend to become pregnant during the trial period. Male participants with partners who are, or intend to become, pregnant during the trial period. Any other condition which, in the opinion of a physician, would make the participant unsuitable for enrollment or could interfere with the participant participating in and completing the trial. Participant who had a life-threatening serious adverse event during the screening period. A participant must not be a member or a family member of the personnel of the investigational or sponsor staff directly involved with this trial. Protocol-specified hematologic, biochemical, and serologic criteria (growth factors may not be used to achieve trial entry requirements). Serum albumin below the lower limit of normal (LLN) of laboratory reference range. Thyroid-stimulating hormone (TSH) >1.2 x Upper Limit of Normal (ULN) or <0.8 x LLN of laboratory reference. Serum creatinine >ULN of the laboratory reference. Protocol-specified serum glucose concentrations. Prothrombin time/partial thromboplastin time (PT/PTT) values >10% above laboratory reference range. Protocol-specified alpha fetoprotein concentrations.

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treated/Not Randomized<br>Participants received 4 weeks of PEG2b/RBV followed by 24 or 44 weeks of boceprevir plus PEG2b/RBV depending on Hepatitis C Virus RNA (HCV-RNA) levels. Participants continued with this treatment if their serum hemoglobin remained >10 g/dL throughout the 28- or 48-week treatment period. | Drug: Boceprevir<br>* 800 mg given three times a day (TID), orally (PO)<br>* Other names: SCH 503034;Drug: Peginterferon alfa-2b (PEG2b)<br>* 1.5 µg/kg/week given subcutaneously (SC)<br>* Other names: SCH 054031;Drug: Ribavirin (RBV)<br>* Ribavirin weight-based dosing (WBD), 600 to 1400 mg/day given twice daily (BID), orally (PO)<br>* Other names: SCH 018908, Rebetol;|
| Experimental: Ribavirin Dose Reduction<br>After the initiation of treatment with 4 weeks with PEG2b/RBV followed by 24 or 44 weeks of boceprevir, participants who became anemic (serum hemoglobin = ≤10 g/dL) within the 28- or 48-week treatment period and who were randomized to the Ribavirin (RBV) Dose Reduction Arm received reduced doses of RBV for management of the anemia in combination with PEG2b and boceprevir therapies. | Drug: Boceprevir<br>* 800 mg given three times a day (TID), orally (PO)<br>* Other names: SCH 503034;Drug: Peginterferon alfa-2b (PEG2b)<br>* 1.5 µg/kg/week given subcutaneously (SC)<br>* Other names: SCH 054031;Drug: Ribavirin (RBV)<br>* Ribavirin weight-based dosing (WBD), 600 to 1400 mg/day given twice daily (BID), orally (PO)<br>* Other names: SCH 018908, Rebetol;|
| Experimental: Erythropoietin Use<br>After the initiation of treatment with 4 weeks with PEG2b/RBV followed by 24 or 44 weeks of boceprevir, participants who became anemic (serum hemoglobin = ≤10 g/dL) within the 28- or 48-week treatment period and who were randomized to the Erythropoietin Use Arm received erythropoietin for management of the anemia in addition to PEG2b/RBV and boceprevir therapies. | Drug: Boceprevir<br>* 800 mg given three times a day (TID), orally (PO)<br>* Other names: SCH 503034;Drug: Peginterferon alfa-2b (PEG2b)<br>* 1.5 µg/kg/week given subcutaneously (SC)<br>* Other names: SCH 054031;Drug: Ribavirin (RBV)<br>* Ribavirin weight-based dosing (WBD), 600 to 1400 mg/day given twice daily (BID), orally (PO)<br>* Other names: SCH 018908, Rebetol;Drug: Erythropoietin<br>* Initial dose of 40,000 Units given subcutaneously (SC) once weekly (QW), with dose adjustment as necessary to achieve and maintain serum hemoglobin levels of 10-12 g/dL<br>* Other names: Procrit, Eprex;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Sustained Virologic Response (SVR) | SVR was defined as undetectable plasma Hepatitis C Virus ribonucleic acid (HCV-RNA) at Follow-up Week 24 | At Follow-up Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Discontinued Treatment | Cumulative discontinuation was defined as the sum of discontinuations due to adverse events, viral breakthrough/resistance, detectable HCV-RNA and futility rules (<2-log10 decline in HCV-RNA at Treatment Week 12, ≥ Lower Limit of Quantification [LLQ] HCV-RNA at Treatment Week 24), and other (noncompliance, withdrawal of consent, lost to follow-up). | From Study Day 1 up to Study Treatment Week 48 |