A Study of Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir With or Without Sofosbuvir and Ribavirin in Direct-Acting Antiviral Agent Treatment-Experienced Adults With Chronic Hepatitis C Virus Infection

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and efficacy of ombitasvir/paritaprevir/ritonavir and dasabuvir with or without sofosbuvir (SOF) and ribavirin (RBV) in DAA treatment-experienced adults with Genotype 1 Chronic Hepatitis C Virus infection. This study will contain 2 parts. Part 1: Approximately 20 participants and at least 10 of the 20 participants previously treated with the combination of ombitasvir/paritaprevir/ritonavir and dasabuvir, with or without RBV, and experienced treatment failure. Part 2: Approximately 10 participants and all participants previously treated with SOF/ledipasvir and experienced treatment failure.

Detailed Description
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Efficacy, safety, and demographic analyses were performed separately for the 2 study parts using the intent-to-treat (ITT) population, which consists of all enrolled participants who received at least one dose of study drug.

Official Title
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An Open-Label Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of Ombitasvir/ABT-450/Ritonavir (Ombitasvir/ABT-450/r) and Dasabuvir Co-administered With or Without Sofosbuvir (SOF) and Ribavirin (RBV) in Direct-Acting Antiviral Agent (DAA) Treatment-Experienced Adults With Genotype 1 Chronic Hepatitis C Virus (HCV) Infection

Conditions
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Chronic Hepatitis C Infection

Intervention / Treatment
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* Drug: ombitasvir/paritaprevir/ritonavir and dasabuvir
* Drug: Sofosbuvir
* Drug: Ribavirin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: History of previous direct acting antiviral (DAA) therapy failure; Part 2 only: history of previous direct acting antiviral (DAA) therapy failure and received at least 8 weeks of SOF/ledipasvir; participant must be treatment naïve to all other anti-HCV therapies HCV genotype 1 infection Females must be post-menopausal, of non-child bearing potential or practicing specific forms of birth control Exclusion Criteria: Positive screen for hepatitis B surface antigen or anti-human immunodeficiency virus antibody Discontinuation of the prior DAA treatment for reasons other than virologic failure Confirmed presence of hepatocellular carcinoma Abnormal lab tests

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 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: 3-DAA with or without SOF and RBV<br>3-DAA (ombitasvir/paritaprevir/ritonavir once daily [QD] and dasabuvir twice daily [BID]) with and without sofosbuvir (SOF) QD and with or without ribavirin (RBV) BID for 12 or 24 weeks | Drug: ombitasvir/paritaprevir/ritonavir and dasabuvir<br>* tablet, ombitasvir coformulated with paritaprevir and ritonavir; tablet, dasabuvir<br>* Other names: dasabuvir also known as ABT-333;Drug: Sofosbuvir<br>* tablet<br>* Other names: Sovaldi;Drug: Ribavirin<br>* tablet<br>* Other names: RBV;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Part 1 Participants With Sustained Virologic Response 12 (SVR12) Weeks Posttreatment | SVR12 was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification [<LLOQ]) 12 weeks after the last dose of study drug. | 12 weeks after the last dose of active drug | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Part 2 Participants With Sustained Virologic Response 12 (SVR12) Weeks Post-treatment | SVR12 was defined as plasma HCV RNA level <LLOQ 12 weeks after the last dose of study drug | 12 weeks after the last dose of active drug | 
| Percentage of Participants With On-treatment Virologic Failure | On-treatment virologic failure was defined as confirmed HCV RNA ≥ LLOQ after < LLOQ during treatment, confirmed increase of > 1 log (subscript)10(subscript) IU/mL above the lowest post-baseline HCV RNA during treatment, or HCV RNA ≥ LLOQ persistently during treatment with at least 6 weeks of treatment. | Up to week 24 | 
| Percentage of Participants With Post-Treatment Relapse | Post-treatment relapse was defined as confirmed HCV RNA ≥ LLOQ between end of treatment and 12 weeks after the last dose of study drug among participants completing treatment and with HCV RNA < LLOQ at the end of treatment. | Within 12 weeks after the last actual dose of active study drug | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatitis C, Interferon-Free, Treatment Experienced, Chronic Hepatitis C, Hepatitis C Virus