Boceprevir Treatment in Participants With Chronic Hepatitis C Genotype 1 Deemed Nonresponders to Peginterferon/Ribavirin (P05514)

Study Overview
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Brief Summary
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This is a single-arm, multicenter study of boceprevir (BOC) in combination with peginterferon plus ribavirin (PEG/RBV) in adult chronic hepatitis C (CHC) genotype 1 participants who completed their per-protocol defined treatment and did not achieve sustained viral response (SVR) while in the PEG/RBV control arm(s) of an Schering-Plough Research Institute (SPRI) study of BOC combination therapy. Participants who are able to enroll in this study within 2 weeks after the last dose of PEG/RBV in previous protocol are to receive BOC+ PEG/RBV for up to 44 weeks followed by 24 weeks post-treatment follow-up. Participants who are not able to enroll in this study within 2 weeks after the last dose of PEG/RBV in previous protocol are to receive PEG/RBV for 4 weeks followed by BOC+ PEG/RBV for up to 44 weeks, with 24 weeks post-treatment follow-up.

Official Title
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A Single-Arm Study to Provide Boceprevir Treatment in Subjects With Chronic Hepatitis C Genotype 1 Deemed Nonresponders to Peginterferon/Ribavirin in Previous Schering-Plough Boceprevir Studies

Conditions
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Hepatitis C, Chronic

Intervention / Treatment
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* Drug: Boceprevir
* Biological: Peginterferon alfa-2b (SCH 54031)
* Drug: Ribavirin (SCH 18908)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant must have been assigned to a PEG/RBV control arm in a previous SPRI study of BOC, must have completed treatment as per protocol, and have been compliant with all study treatment and scheduled procedures within the previous study. Participant must have received at least 12 weeks of treatment with PEG/RBV and must have discontinued treatment in the previous study due to the futility rule (as defined in the previous protocol), had virologic breakthrough, or relapse. Participant must have had detectable HCV-RNA upon completion of the previous study. Participant and participant partner(s) must each agree to use acceptable methods of contraception for at least 2 weeks prior to starting any study treatment and to continue until at least 6 months after the last doses of study drugs, or longer if dictated by local regulations. Participant must be willing to give written informed consent. Exclusion Criteria: All participant exclusion criteria from the SPRI clinical study in which the participant participated prior to qualifying for this study will apply in this study, EXCEPT for the following: Treatment with RBV within 90 days and any interferon-alpha within 1 month of the enrollment is not exclusionary in P05514. Participation in any other SPRI clinical trial within 30 days of enrollment in this study is not exclusionary. Use of growth factor at the entry of the study is allowed if it was prescribed in the previous study. Laboratory criteria of thyroid-stimulating hormone (TSH) do not apply. Laboratory criteria of hemoglobin, neutrophils, and platelets do not apply, unless they met dose reduction/interruption/discontinuation criteria in the previous study. Participants who develop moderate depression in the previous study and continue to be stable and well controlled are not excluded Participants who had the opportunity to receive boceprevir in the previous study. Participants requiring discontinuation, interruption, or dose reduction of RBV for more than 2 weeks in the previous study. Participants requiring discontinuation, interruption, or dose reduction of PEG to less than two-thirds of the assigned starting dose for more than 2 weeks in the previous study. Participants who experienced a life-threatening SAE considered at least possibly related to study drugs by the investigator or sponsor in the previous study.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BOC + PEG/RBV<br>Participants who enrolled within 2 weeks after the last dose of PEG/RBV in previous protocol received boceprevir (BOC) + peginterferon/ribavirin (PEG/RBV) for up to 44 weeks followed by 24 weeks post-treatment follow-up. Participants who did not enroll within 2 weeks after the last dose of PEG/RBV in previous protocol received PEG/RBV for 4 weeks followed by BOC + PEG/RBV for up to 44 weeks, with 24 weeks post-treatment follow-up. | Drug: Boceprevir<br>* Boceprevir, 200-mg capsules, 800 mg three times a day (TID) orally (PO)<br>* Other names: SCH 503034;Biological: Peginterferon alfa-2b (SCH 54031)<br>* Peginterferon alfa-2b 1.5 µg/kg/week subcutaneously (SC)<br>* Other names: PegIntron, PEG;Drug: Ribavirin (SCH 18908)<br>* Ribavirin weight-based dosing (WBD) 600 mg/day to 1400 mg/day PO divided twice daily (BID).<br>* Other names: Rebetol, RBV;|

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 at Follow-Up Week 24 (SVR24); | SVR24 was defined as undetectable Hepatitis C Virus ribonucleic acid (HCV-RNA) at Follow-up Week (FW) 24. SVR rates were evaluated by the prior interferon response (e.g., log drop from baseline at TW 4 or TW 12) in the previous studies. | From start of 4-week PEG/RBV lead-in therapy or 44-week BOC/PR treatment through Follow-Up Week (FW) 24 (up to 68 weeks) | 
| Percentage of Participants With Adverse Events (AEs) Leading to Dose Modification (DM) or Discontinuation (DC), Treatment-Related Serious AEs (SAEs), Neutrophil Count <0.75 × 10^9/L, or Hemoglobin (Hgb) <10 g/dL | AE= any untoward medical occurrence in a participant administered a pharmaceutical product/biologic (at any dose), whether or not considered related to the use of that product. Included the onset of new illness and the exacerbation of pre-existing conditions. Clinically significant laboratory abnormalities that required intervention/additional therapy, required a dose modification, or were associated with a clinical manifestation were considered AEs. SAE= any adverse drug or biologic or device experience occurring at any dose resulting in death, was life-threatening, was persistent or caused significant disability/incapacity, required in-patient hospitalization or prolonged hospitalization, or was a congenital anomaly or birth defect. | From start of 4-week PEG/RBV lead-in therapy or 44-week BOC/PR treatment through FW 24 (up to 68 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Early Virologic Response (EVR) | EVR was defined as undetectable HCV-RNA at TW 12 of BOC + PEG/RBV. EVR rates were evaluated by the prior interferon response (e.g., log drop from baseline at TW 4 or TW 12) in the previous studies. | From TW 1 to TW 12 |