Safety and Efficacy of Boceprevir in Asia Pacific Participants With Chronic Hepatitis C Genotype 1 (P07063)

Study Overview
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Brief Summary
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This study will assess the efficacy of boceprevir (BOC) in combination with PegIntron (pegylated interferon alfa-2b) (PEG) and ribavirin (RBV) in response guided therapy compared to the efficacy of standard-of-care therapy alone in adult subjects with chronic hepatitis C (CHC) genotype 1 who failed prior treatment with pegylated interferon and RBV in the Asia Pacific population. The primary hypothesis is that the proportion of participants achieving sustained virologic response in the experimental therapy regimen (BOC/PEG+RBV) is superior to that in the control arm (Placebo/PEG+RBV), in the Full Analysis Set (FAS) population.

Official Title
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Safety and Efficacy of Boceprevir in Combination With Peginterferon Plus Ribavirin for Treatment of Asia Pacific Subjects With Chronic Hepatitis C Genotype 1 Who Failed Prior Treatment With Pegylated Interferon Plus Ribavirin

Conditions
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Hepatitis C, Chronic

Intervention / Treatment
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* Drug: Boceprevir (BOC)
* Drug: Placebo to boceprevir
* Drug: Peginterferon alfa-2b (PEG)
* Drug: Ribavirin (RBV)
* Drug: Cross-Over Boceprevir Treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Previously documented CHC genotype 1 infection. Other or mixed genotypes are not eligible. Liver biopsy with histology consistent with CHC and no other etiology. Participants with cirrhosis must have an ultrasound/imaging study within 6 months of screening (or between screening and Day 1) with no findings suspicious for hepatocellular carcinoma Failed previous treatment (of at least 12 weeks) with pegylated interferon (alfa-2a or alfa-2b) plus RBV Weight between 40 kg and 125 kg, inclusive Of 'local' ancestral descent Sexually active males and females of child-bearing potential must agree to use a medically accepted method of contraception Exclusion Criteria: Co-infected with the human immunodeficiency virus (HIV) or hepatitis B virus. Required discontinuation of previous interferon or RBV regimen for an adverse event considered to be possibly or probably related to RBV and/or interferon. Treatment with RBV within 90 days and any interferon-alpha within 1 month prior to screening. Treatment for hepatitis C with any investigational medication or prior treatment with herbal remedies with known hepatotoxicity. Treatment with any investigational drug or participation in any interventional clinical trial within 30 days of the screening visit. Evidence of decompensated liver disease including, but not limited to, a history or presence of clinical ascites, bleeding varices, or hepatic encephalopathy. Diabetes and/or hypertension with clinically significant ocular examination findings. Any condition the could interfere with participation in and completion of the trial. Evidence of active or suspected malignancy, or history of malignancy within the last 5 years (except adequately treatment carcinoma in situ and basal cell carcinoma of the skin). Pregnant or breast-feeding.

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Boceprevir<br>PEG + RBV for 4 weeks followed by BOC + PEG + RBV for 32 weeks. At the Treatment Week 36 visit, participants with undetectable HCV-RNA at Treatment Weeks 8 and 12 will proceed to 36 weeks of post-treatment follow-up. Participants with detectable HCV-RNA at Treatment Week 8 and undetectable HCV-RNA at Treatment Week 12 will continue on BOC + PEG + RBV until Treatment Week 36, receive placebo + PEG + RBV until Treatment Week 48, and then proceed to 24 weeks of post-treatment follow-up. Participants with any HCV-RNA result at Treatment Week 8 and detectable HCV-RNA at Treatment Week 12 will discontinue treatment and proceed to 24 weeks of post-treatment follow-up. | Drug: Boceprevir (BOC)<br>* 200 mg capsules, 800 mg three times daily by mouth<br>* Other names: Victrelis;Drug: Placebo to boceprevir<br>* 200 mg placebo capsules, 800 mg three times daily by mouth<br>Drug: Peginterferon alfa-2b (PEG)<br>* 1.5 mcg/kg/week subcutaneously<br>* Other names: Redipen;Drug: Ribavirin (RBV)<br>* 200 mg capsules, weight-based dosing 800 to 1400 mg/day by mouth divided twice daily<br>* Other names: SCH 018908;|
| Active Comparator: Control<br>PEG + RBV for 4 weeks followed by BOC placebo + PEG + RBV for 44 weeks. Participants with undetectable HCV-RNA at Treatment Week 12 and at subsequent assays will continue on placebo + PEG + RBV through Treatment Week 48 and proceed to 24 weeks of post-treatment follow-up. Participants with detectable HCV-RNA at Treatment Week 12 may roll over to Cross-Over BOC treatment beginning with Treatment Week 14. | Drug: Placebo to boceprevir<br>* 200 mg placebo capsules, 800 mg three times daily by mouth<br>Drug: Peginterferon alfa-2b (PEG)<br>* 1.5 mcg/kg/week subcutaneously<br>* Other names: Redipen;Drug: Ribavirin (RBV)<br>* 200 mg capsules, weight-based dosing 800 to 1400 mg/day by mouth divided twice daily<br>* Other names: SCH 018908;Drug: Cross-Over Boceprevir Treatment<br>* At Treatment Week 14, participants in the Placebo group with detectable HCV-RNA at Treatment Week 12 have the option to add boceprevir 800 mg three times daily to the PEG + RBV regimen for up to 32 weeks.<br>* Other names: Victrelis;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants in Korea and Taiwan With Sustained Virologic Response (SVR) at Follow-Up Week 24 - Full Analysis Set (FAS) Population | SVR is defined as undetectable plasma HCV-RNA at Follow-up Week (FW) 24. If FW24 is missing and other HCV-RNA values after FW24 are available, the last available value would be used for FW24. The last observation carried forward (LOCF) method was used to impute missing values; if a participant is missing at and after FW24 and has FW12 data, then FW12 data will be carried forward to FW24. Cross-over participants are considered as non-responders in SVR. | Follow-up Week 24 | 
| Percentage of Participants in India With SVR at Follow-Up Week 24 - FAS Population | SVR is defined as undetectable plasma HCV-RNA at FW24. If FW24 is missing and other HCV-RNA values after FW24 are available, the last available value would be used for FW24. The LOCF method was used to impute missing values; if a participant is missing at and after FW24 and has FW12 data, then FW12 data will be carried forward to FW24. Cross-over participants are considered as non-responders in SVR. | Follow-up Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants in Korea and Taiwan With SVR at Follow-Up Week 24 - Modified Intent-to-Treat (mITT) Population | SVR is defined as undetectable plasma HCV-RNA at FW24. If FW24 is missing and other HCV-RNA values after FW24 are available, the last available value would be used for FW24. The LOCF method was used to impute missing values; if a participant is missing at and after FW24 and has FW12 data, then FW12 data will be carried forward to FW24. Cross-over participants are considered as non-responders in SVR. | Follow-up Week 24 | 
| Percentage of Participants in India With SVR at Follow-Up Week 24 - mITT Population | SVR is defined as undetectable plasma HCV-RNA at FW24. If FW24 is missing and other HCV-RNA values after FW24 are available, the last available value would be used for FW24. The LOCF method was used to impute missing values; if a participant is missing at and after FW24 and has FW12 data, then FW12 data will be carried forward to FW24. Cross-over participants are considered as non-responders in SVR. | Follow-up Week 24 | 
| Percentage of Participants in Korea and Taiwan Achieving Early Virologic Response (EVR) at Treatment Week 8 | Percentage of participants achieving early virologic response (undetectable HCV-RNA at Treatment Week 8) | Treatment Week 8 | 
| Percentage of Participants in India Achieving EVR at Treatment Week 8 | Percentage of participants achieving early virologic response (undetectable HCV-RNA at Treatment Week 8) | Treatment Week 8 | 
| Percentage of Participants With an Adverse Event (AE) of Anemia in Korea and Taiwan | Anemia is a condition in which the number of red blood cells or hemoglobin concentration is insufficient to meet the body's physiologic needs. This measure gives the percentage of participants who experienced an occurrence of modified World Health Organization (WHO) grade 1-4 anemia during the treatment period. A higher grade indicates a higher degree of anemia. This table summarizes the worst category observed within the period per participant per laboratory test (i.e., the lowest value for the hemotologic parameters). | Up to 96 weeks | 
| Percentage of Participants With an AE of Anemia in India | Anemia is a condition in which the number of red blood cells (hemoglobin) is insufficient to meet the body's physiologic needs. This measure gives the percentage of participants who experienced an occurrence of modified WHO grade 1-4 anemia during the treatment period. A higher grade indicates a higher degree of anemia. This table summarizes the worst category observed within the period per participant per laboratory test (i.e., the lowest value for the hemotologic parameters). | Up to 96 weeks | 
| Percentage of Participants With an AE of Neutropenia in Korea and Taiwan | Neutropenia is an abnormally low level of white blood cells (neutrophils). This measure gives the percentage of participants who experienced an occurrence of modified WHO grade 1-4 neutropenia during the treatment phase. A higher grade indicates a higher degree of neutropenia. This table summarizes the worst category observed within the period for each participant. | Up to 96 weeks | 
| Percentage of Participants With an AE of Neutropenia in India | Neutropenia is an abnormally low level of white blood cells (neutrophils). This measure gives the percentage of participants who experienced an occurrence of modified WHO grade 1-4 neutropenia during the treatment phase. A higher grade indicates a higher degree of neutropenia. This table summarizes the worst category observed within the period for each participant. | Up to 96 weeks |