A Study to Evaluate the Safety and Efficacy of ABT-450/Ritonavir/ABT-267; (ABT-267 Also Known as Ombitasvir) and ABT-333 (Also Known as Dasabuvir) Coadministered With Ribavirin (RBV) in Hepatitis C Virus (HCV) Genotype 1-infected Adults With Compensated Cirrhosis

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 ABT-450/ritonavir/ABT-267 (ABT-450/r/ABT-267; ABT-450 also known as paritaprevir; ABT-267 also known as ombitasvir) and ABT-333 (also known as dasabuvir) coadministered with ribavirin (RBV) in hepatitis C virus (HCV) genotype 1-infected adults with compensated cirrhosis.

Detailed Description
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During the treatment period of the study, participants received treatment with ABT-450/ritonavir/ABT-267 and ABT-333 coadministered with RBV for either 12 or 24 weeks. Upon completing the treatment period or premature discontinuation of the treatment period, participants entered a 48-week post-treatment period.

Official Title
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A Randomized, Open-Label Study to Evaluate the Safety and Efficacy of ABT-450/Ritonavir/ABT-267 (ABT-450/r/ABT-267) and ABT-333 Coadministered With Ribavirin (RBV) in Adults With Genotype 1 Chronic Hepatitis C Virus (HCV) Infection and Cirrhosis (TURQUOISE-II)

Conditions
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Chronic Hepatitis C Infection, Compensated Cirrhosis

Intervention / Treatment
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* Drug: ABT-450/r/ABT-267, ABT-333
* Drug: Ribavirin (RBV)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Females must be practicing specific forms of birth control on study treatment, or be post-menopausal for more than 2 years or surgically sterile Male or female between 18 and 70 years, inclusive, at time of Screening. Chronic HCV-infection prior to study enrollment. Screening laboratory result indicating HCV genotype 1-infection. Compensated cirrhosis defined as a Child-Pugh Score of less than or equal to 6 at Screening Subject has plasma HCV RNA level greater than 10,000 IU/mL at Screening. Exclusion Criteria: Significant liver disease with any cause other than HCV as the primary cause Positive test result for Hepatitis B surface antigen (HBsAg) or anti-Human Immunodeficiency virus antibody (HIV Ab) at screening. Prior therapy with direct acting antiviral agents for the treatment of HCV, including telaprevir and boceprevir. Any current or past clinical evidence of Child-Pugh B or C Classification or clinical history of liver decompensation including ascites (noted on physical exam), variceal bleeding or hepatic encephalopathy. A positive screening ultrasound for hepatocellular carcinoma (HCC) confirmed with a subsequent CT Scan or MRI during the screening period.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: ABT-450/r/ABT-267 and ABT-333, plus RBV for 12 weeks<br>ABT-450/r/ABT-267 (150/100/25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based ribavirin (RBV; 1,000 mg/day if <75 kg or 1,200 mg/day if ≥75 kg, divided twice daily) for 12 weeks | Drug: ABT-450/r/ABT-267, ABT-333<br>* Tablet; ABT-450 coformulated with ritonavir and ABT-267; ABT-333 tablet<br>* Other names: Viekira Pak; ABT-450 also known as paritaprevir; ABT-267 also known as ombitasvir; ABT-333 also known as dasabuvir;Drug: Ribavirin (RBV)<br>* Capsule<br>|
| Experimental: ABT-450/r/ABT-267 and ABT-333, plus RBV for 24 weeks<br>ABT-450/r/ABT-267 (150/100/25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based ribavirin (RBV; 1,000 mg/day if <75 kg or 1,200 mg/day if ≥75 kg, divided twice daily) for 24 weeks | Drug: ABT-450/r/ABT-267, ABT-333<br>* Tablet; ABT-450 coformulated with ritonavir and ABT-267; ABT-333 tablet<br>* Other names: Viekira Pak; ABT-450 also known as paritaprevir; ABT-267 also known as ombitasvir; ABT-333 also known as dasabuvir;Drug: Ribavirin (RBV)<br>* Capsule<br>|

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 12 Weeks Post-treatment | The percentage of participants with sustained virologic response (plasma Hepatitis C virus ribonucleic acid [HCV RNA] level less than the lower limit of quantitation [< LLOQ]) 12 weeks after the last dose of study drug. | 12 weeks after the last actual dose of study drug | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment in the 24-week Arm Compared to the 12-week Arm | A sustained virologic response is defined as plasma Hepatitis C virus ribonucleic acid (HCV RNA) less than the lower limit of quantification (< LLOQ) 12 weeks after the last dose of study drug. | 12 weeks after the last actual dose of study drug | 
| Percentage of Participants in Each Arm With On-treatment Virologic Failure During the Treatment Period | Virologic failure during treatment was defined as rebound (confirmed HCV RNA greater than or equal to the lower limit of quantitation [≥ LLOQ] after HCV RNA < LLOQ during treatment, or confirmed increase from the lowest value post baseline in HCV RNA [2 consecutive HCV RNA measurements > 1 log(subscript)10(subscript) IU/mL above the lowest value post baseline] at any time point during treatment), or fail to suppress (HCV RNA ≥ LLOQ persistently during treatment with at least 6 weeks [≥ 36 days] of treatment). | Baseline (Day 1), and Treatment Weeks 1, 2, 4, 6, 8, 10, 12, 16, 20, and 24 | 
| Percentage of Participants With Virologic Relapse After Treatment | Participants were considered to have virologic relapse after treatment if they had confirmed quantifiable plasma Hepatitis C virus ribonucleic acid (HCV RNA) ≥ lower limit of quantification (LLOQ) between the end of treatment and 12 weeks after the last dose of study drug among participants who completed treatment with HCV RNA < LLOQ at the end of treatment. | within 12 weeks after the last dose of study drug | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cirrhosis, Hepatitis C, Child Pugh A, Compensated Cirrhosis, Hepatitis C Genotype 1, Cirrhotic, Chronic Hepatitis C, Hepatitis C Virus, ombitasvir, paritaprevir, dasabuvir, Interferon-Free, Viekira Pak