A Study to Evaluate the Safety and Effect of the Experimental Drugs ABT-450/Ritonavir/ABT-267 (ABT-450/r/ABT-267) and ABT-333 in Subjects With Chronic Hepatitis C

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and antiviral activity 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) with and without ribavirin (RBV) in patients with chronic hepatitis C virus genotype 1b (HCV GT1b) infection without cirrhosis.

Detailed Description
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A randomized, open-label, multicenter study to evaluate the safety and antiviral activity of the combination of ABT-450/ritonavir/ABT-267 (ABT-450/r/ABT-267) and ABT-333 with and without ribavirin (RBV) in treatment-experienced, noncirrhotic participants with chronic hepatitis C virus genotype 1b (HCV GT1b) infection.

Official Title
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A Randomized, Open-Label, Multicenter Study to Evaluate the Safety and Antiviral Activity of the Combination of ABT-450/Ritonavir/ABT-267 (ABT 450/r/ABT-267) and ABT-333 With and Without Ribavirin in Treatment-Experienced Subjects With Genotype 1b Chronic Hepatitis C Virus (HCV) Infection (PEARL-II)

Conditions
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Chronic Hepatitis C Infection

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


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 Chronic hepatitis C, genotype 1b-infection (HCV RNA level greater than or equal to 10,000 IU/mL at screening) Subject's hepatitis C virus genotype is subgenotype 1b at Screening without co infection with any other genotype/subgenotype. Exclusion Criteria: Significant liver disease with any cause other than HCV as the primary cause Positive hepatitis B surface antigen or anti-human immunodeficiency virus antibody Positive screen for drugs or alcohol Use of contraindicated medications within 2 weeks of dosing

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<br>ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) 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;Drug: Ribavirin<br>* Tablet<br>|
| Experimental: ABT-450/r/ABT-267 and ABT-333<br>ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg 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;|

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 After Treatment; Primary Analyses | 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. The LLOQ for the assay was 25 IU/mL. The primary efficacy endpoints were noninferiority of the percentage of participants who achieved sustained virologic response 12 weeks after treatment in each treatment arm (ABT-450/r/ABT-267 and ABT-333 with and without RBV) compared with the historical control rate for noncirrhotic, treatment-experienced participants with HCV GT1b infection treated with telaprevir and peginterferon (pegIFN)/RBV. | 12 weeks after last dose of study drug | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Hemoglobin Decrease to Below the Lower Limit of Normal (LLN) At End of Treatment | The percentage of participants with a decrease in hemoglobin from greater than or equal to the lower limit of normal (≥ LLN) at baseline to < LLN at the end of treatment. | Baseline (Day 1) and Week 12 (End of Treatment) | 
| Percentage of Participants With Sustained Virologic Response 12 Weeks After Treatment; Secondary Analyses | 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. The secondary efficacy endpoints were superiority of the percentage of participants who achieved sustained virologic response 12 weeks after treatment in each treatment arm (ABT-450/r/ABT-267 and ABT-333 with and without RBV) compared with the historical control rate for noncirrhotic, treatment-experienced participants with HCV GT1b treated with telaprevir and pegIFN/RBV; and the noninferiority of the percentage of participants who achieved sustained virologic response 12 weeks after treatment who received ABT-450/r/ABT-267 and ABT-333 compared with those who received ABT-450/r/ABT-267 and ABT-333, plus RBV. | 12 weeks after last dose of study drug | 
| Percentage of Participants With Virologic Failure During Treatment | 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 log10 IU/mL above the lowest value post baseline] at any time point during treatment), or failure 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, and 12 | 
| Percentage of Participants With Virologic Relapse After Treatment | Participants who completed treatment with plasma HCV RNA less than the lower limit of quantification (<LLOQ) at the end of treatment were considered to have virologic relapse if they had confirmed HCV RNA ≥ LLOQ during the post-treatment period. 95% CI was calculated using the Wilson score method for the single proportion because the point estimate was 0%. | Between End of Treatment (Week 12) and Post-treatment (up to Week 12 Post-Treatment) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatitis C virus, Hepatitis C Genotype 1, Hepatitis C, Interferon-Free, Chronic Hepatitis C, Ombitasvir, Ribavirin, Viekira PAK, Dasabuvir, Paritaprevir