An Observational Study Examining the Use of Triple Combination Therapy With Boceprevir, Peginterferon Alfa-2a and Ribavirin in the Re-Treatment of Chronic Hepatitis C Patients

Study Overview
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Brief Summary
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This prospective, national, multicenter, non-interventional study examined the use of triple combination therapy with boceprevir, pegylated interferon (peginterferon) alfa-2a and ribavirin in re-treating participants with genotype 1 chronic hepatitis C (CHC) infection. Dosing and treatment duration were at the discretion of the investigator in accordance with local clinical practice and local labeling. Participants were to be observed for the duration of their triple combination therapy and for up to 24 weeks thereafter.

Official Title
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Non-interventional Study to Observe Triple Combination Therapy With Boceprevir or Simeprevir Plus Peginterferon Alfa-2a Plus Ribavirin for Re-treatment of Chronic Hepatitis C in Hungary (IMPERIAL)

Conditions
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Hepatitis C, Chronic

Intervention / Treatment
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* Drug: Boceprevir
* Drug: Simeprevir
* Drug: Pegylated Interferon (Peginterferon) Alfa-2a
* Drug: Ribavirin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years of age or over Genotype 1 CHC infection Prior unsuccessful treatment with peginterferon alfa plus ribavirin (null-response, partial response and relapsed participants) Receiving triple combination therapy with boceprevir, peginterferon alfa-2a and ribavirin according to standard of care and in line with local labeling Enrollment in the study no later than 4 weeks after start of triple combination therapy (including peginterferon alfa-2a and ribavirin lead-in phase) Exclusion Criteria: Naïve participants not responding to peginterferon alfa plus ribavirin at week 4 (HCV RNA drop < 1 log10) or at week 12 (HCV RNA >/= 15 international units/milliliter [IU/mL]) and switching to triple combination therapy with boceprevir

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Triple Combination Therapy<br>Participants who demonstrated genotype 1 chronic hepatitis C infection and had a history of unsuccessful treatment with pegylated interferon (peginterferon) alfa + ribavirin, and who were subjected to receive a triple combination therapy with simeprevir or boceprevir plus peginterferon alfa-2a and ribavirin were observed. | Drug: Boceprevir<br>* Boceprevir administered according to corresponding summary of product characteristics (SmPC).<br>* Other names: Victrelis;Drug: Simeprevir<br>* Simeprevir administered according to corresponding summary of product characteristics (SmPC).<br>* Other names: Olysio;Drug: Pegylated Interferon (Peginterferon) Alfa-2a<br>* Pegylated interferon (peginterferon) alfa-2a according to corresponding summary of product characteristics (SmPC).<br>* Other names: Pegasys;Drug: Ribavirin<br>* Ribavirin according to corresponding summary of product characteristics (SmPC).<br>* Other names: Copegus;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sustained Virological Response 24 (SVR24) Rate | The SVR 24 rate is defined as percentage of participants with Hepatitis C virus (HCV) Ribonucleic Acid (RNA) less than 15 international unit/milliliter (IU/mL) after the 24-weeks follow-up. | 24 weeks after end of treatment (EOT) at Week 72 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Virological Response | Virological response is defined as HCV RNA <15 IU/mL. | Weeks 4, 8, 12, and 24 | 
| Number of Participants With Virological Breakthrough | Virological breakthrough is defined as either HCV RNA >=15 IU/mL in participants with prior virological response or as an increase in HCV RNA >/=1 log10 above nadir. | Up to Week 48 | 
| Number of Participants With Virological Relapse | Virological response is defined as HCV RNA >/=15 IU/mL during the treatment free follow-up period in participants with virological response at the end of treatment. | Week 49 up to Week 72 | 
| Number of Participants With Treatment Discontinuation Due to Futility | Treatment discontinuation due to futility is defined as HCV RNA drop <3 log10 at Week 8, HCV RNA >/=100 IU/mL at Week 12, or HCV RNA >/=15 IU/mL at Week 24. | Up to Week 48 | 
| Number of Participants With Treatment Discontinuation | Treatment discontinuation is reported by sub-categories of reasons for treatment discontinuation. Futility rule is defined as HCV RNA drop <3 log10 at Week 8, HCV RNA >/=100 IU/mL at Week 12, or HCV RNA >/=15 IU/mL at Week 24. | Up to Week 48 | 
| Number of Participants With Adverse Events | An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. | Up to 72 weeks | 
| Percentage of Participants With Positive Predictive Value of Participant Demographics for SVR Rate | Demographic characteristics recorded were age and gender. Predictive value of these characteristics for SVR rate was to be assessed. | Screening (before Week 1) | 
| Percentage of Participants With Positive Predictive Value of Liver Fibrosis | The following sub-categories of liver fibrosis were determined in this study: 1) no cirrhosis, 2) bridging fibrosis and 3) cirrhosis. Predictive value of these sub-categories of liver fibrosis for SVR rate was to be assessed. | Screening (before Week 1) | 
| Predictive Value of HCV Disease Characteristics | HCV disease characteristics evaluated were HCV genotype (subtype), including HCV 1(a) and HCV 1(b). Predictive value of these disease characteristics for SVR rate were to be assessed. | Screening (before Week 1) | 
| Percentage of Participants With Positive Predictive Value of Previous Virological Response (Null-response, Partial Response, or Relapse) | Previous virological response was sub-categorized into the following categories: null-response, partial response, or relapse. Predictive value of these sub-categories for SVR rate were to be assessed. | Up to 72 weeks |