A Study to Evaluate Chronic Hepatitis C Infection in Treatment Experienced Adults

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 and ABT-267 (ABT-450/r/ABT-267; ABT-267 also known as ombitasvir) and ABT-333 (also known as dasabuvir) co-administered with ribavirin (RBV) in hepatitis C virus genotype 1 infected treatment-experienced adults.

Official Title
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A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of ABT450/Ritonavir/ABT-267 (ABT-450/r/ABT-267) and ABT-333 Co-administered With Ribavirin (RBV) in Treatment-Experienced Adults With Genotype 1 Chronic Hepatitis C Virus (HCV) Infection (SAPPHIRE-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
* Drug: Placebo for ABT-450/r/ABT-267
* Drug: Placebo for ABT-333
* Drug: Placebo for ribavirin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Females must be post-menopausal for at least 2 years or surgically sterile or practicing specific forms of birth control. Chronic hepatitis C, genotype 1 infection and HCV RNA level greater than 10,000 IU/mL at screening. Previous treatment failure of peg-interferon and ribavirin (pegIFN and RBV). No evidence of liver cirrhosis. Exclusion Criteria: Positive screen for drugs or alcohol. Significant sensitivity to any drug. Use of contraindicated medications within 2 weeks of dosing. Certain predefined abnormal laboratory tests. Positive hepatitis B surface antigen or anti-human immunodeficiency virus antibody.

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ABT-450/r/ABT-267 and ABT-333, plus RBV<br>Double-blind ABT-450/r/ABT-267 (150 mg/100 mg/25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based ribavirin (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>* Capsule (double-blind treatment period), tablet (open-label treatment period)<br>|
| Experimental: Placebo Followed by ABT-450/r/ABT-267 and ABT-333, plus RBV<br>Double-blind placebo for 12 weeks, followed by open-label ABT-450/r/ABT-267 (150 mg/100 mg/25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based RBV (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>* Capsule (double-blind treatment period), tablet (open-label treatment period)<br>Drug: Placebo for ABT-450/r/ABT-267<br>* Tablet<br>Drug: Placebo for ABT-333<br>* Tablet<br>Drug: Placebo for ribavirin<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 After 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 active study drug | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Normalization of Alanine Aminotransferase (ALT) at Final Treatment Visit During the Double-Blind Treatment Period | Normalization is defined as alanine aminotransferase less than or equal to the upper limit of normal (ULN) at final treatment visit for participants with alanine aminotransferase greater than ULN at baseline. | At 12 weeks | 
| Percentage of HCV Genotype 1a-infected Participants With Sustained Virologic Response 12 Weeks After 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 active study drug | 
| Percentage of HCV Genotype 1b-infected Participants With Sustained Virologic Response 12 Weeks After 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 active study drug | 
| Percentage of Participants With On-treatment Virologic Failure During the Double-blind Treatment Period: ABT-450/r/ABT-267 and ABT-333, Plus RBV Arm | Virologic failure was defined as rebound (hepatitis C virus ribonucleic acid [HCV RNA] ≥ lower limit of quantification [LLOQ] after HCV RNA < LLOQ or increase in HCV RNA of at least 1 log10 IU/mL) or failure to suppress (all on-treatment values of plasma HCV RNA ≥ LLOQ with at least 36 days of treatment) during treatment. | 12 weeks after the last actual dose of active study drug | 
| Percentage of Participants With Virologic Relapse After Treatment: ABT-450/r/ABT-267 and ABT-333, Plus RBV Arm | Participants were considered to have virologic relapse after treatment if they had confirmed quantifiable plasma hepatitis C virus ribonucleic acid (HCV RNA) greater than or equal to the 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 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, Treatment-Experienced, Null responder, Partial Responder, Chronic Hepatitis, Hepatitis C Genotype 1, Interferon-Free, Relapser, Non responder, Viekira Pak, ombitasvir, ribavirin, ritonavir, paritaprevir, dasabuvir