A Study to Evaluate the Safety and Antiviral Effect of Multiple Doses of ABT-493 and ABT-530 in Adults With Genotype 1 Hepatitis C Virus (HCV)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and antiviral effect of multiple doses of ABT-493 and ABT-530 in adults with genotype 1 HCV.

Official Title
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A Randomized, Open-Label, Dose Ranging Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of Multiple Doses of ABT-493 and ABT-530 in Adult Subjects With Genotype 1 Chronic Hepatitis C Virus (HCV) Infection

Conditions
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Chronic Hepatitis C, Hepatitis C Virus, Compensated Cirrhosis

Intervention / Treatment
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* Drug: ABT-493
* Drug: ABT-530
* 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: Chronic HCV infection prior to study enrollment. Screening laboratory result indicating HCV genotype 1-infection. Subject has plasma HCV RNA level greater than 10,000 IU/mL at Screening. Per local standard, subject is considered to be non-cirrhotic or to have compensated cirrhosis. Exclusion Criteria: History of severe, life-threatening or other significant sensitivity to any drug. Positive test result for Hepatitis B surface antigen (HBsAg) or anti-Human Immunodeficiency Virus antibody (HIV Ab). Prior therapy for the treatment of HCV. Any current or past clinical evidence of Child Pugh B or C classification of clinical history of liver decompensation including ascites (noted on physical exam), variceal bleeding or hepatic encephalopathy. Any cause of liver disease other than chronic HCV infection.

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: Arm 1 Non-cirrhotic<br>ABT-493 Dose A (100 mg once daily [QD]) for 3 days, followed by 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-493<br>* Tablet<br>* Other names: glecaprevir;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 (RBV)<br>* Tablet<br>|
| Experimental: Arm 2 Non-cirrhotic<br>ABT-493 Dose B (400 mg QD) for 3 days, followed by 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-493<br>* Tablet<br>* Other names: glecaprevir;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 (RBV)<br>* Tablet<br>|
| Experimental: Arm 3 Non-cirrhotic<br>ABT-493 Dose C (700 mg QD) for 3 days, followed by 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-493<br>* Tablet<br>* Other names: glecaprevir;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 (RBV)<br>* Tablet<br>|
| Experimental: Arm 4 Non-cirrhotic<br>ABT-493 Dose D (200 mg QD) for 3 days, followed by 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-493<br>* Tablet<br>* Other names: glecaprevir;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 (RBV)<br>* Tablet<br>|
| Experimental: Arm 5 Compensated cirrhotic<br>ABT-493 Dose E (200 mg QD) for 3 days, followed by 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-493<br>* Tablet<br>* Other names: glecaprevir;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 (RBV)<br>* Tablet<br>|
| Experimental: Arm 6 Non-cirrhotic<br>ABT-530 Dose A (15 mg QD) for 3 days, followed by 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-530<br>* Tablet<br>* Other names: pibrentasvir;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 (RBV)<br>* Tablet<br>|
| Experimental: Arm 7 Non-cirrhotic<br>ABT-530 Dose B (120 mg QD) for 3 days,followed by 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-530<br>* Tablet<br>* Other names: pibrentasvir;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 (RBV)<br>* Tablet<br>|
| Experimental: Arm 8 Non-cirrhotic<br>ABT-530 Dose C (400 mg QD) for 3 days, followed by 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-530<br>* Tablet<br>* Other names: pibrentasvir;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 (RBV)<br>* Tablet<br>|
| Experimental: Arm 9 Non-cirrhotic<br>ABT-530 Dose D (40 mg QD) for 3 days, followed by 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-530<br>* Tablet<br>* Other names: pibrentasvir;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 (RBV)<br>* Tablet<br>|
| Experimental: Arm 10 Compensated cirrhotic<br>ABT-530 Dose E (120 mg QD) for 3 days, followed by 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-530<br>* Tablet<br>* Other names: pibrentasvir;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 (RBV)<br>* Tablet<br>|
| Experimental: Arm 11 Non-cirrhotic<br>ABT-493 Dose F (300 mg QD) for 3 days, followed by 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-493<br>* Tablet<br>* Other names: glecaprevir;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 (RBV)<br>* Tablet<br>|
| Experimental: Arm 12 Non-cirrhotic<br>ABT-530 Dose F (≤ 400 mg) for 3 days, followed by 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-530<br>* Tablet<br>* Other names: pibrentasvir;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 (RBV)<br>* Tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximal Decrease From Baseline in log10 HCV RNA Levels During ABT-493 or ABT-530 Monotherapy Treatment | Maximal decrease from baseline in log10 HCV RNA levels during ABT-493 or ABT-530 monotherapy treatment. The baseline value was the last measurement before the first dose of monotherapy on Day 1. | Day 1 through prior to first dose of the combination regimen on Study Day 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) | 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 combination study drug. | 12 weeks after last actual dose of combination study drug | 
| Percentage of Participants With On-treatment Virologic Failure | On-treatment virologic failure was defined as confirmed HCV RNA ≥ LLOQ after HCV RNA < LLOQ during combination treatment; confirmed increase of > 1 log(subscript)10(subscript) IU/mL above the lowest value post-baseline in HCV RNA during combination treatment; or HCV RNA ≥ LLOQ at end of combination treatment with at least 6 weeks of combination treatment. | Up to 87 days | 
| Percentage of Participants With Post-treatment Relapse | Post-treatment relapse was defined as confirmed HCV RNA ≥ LLOQ between the end of treatment and 12 weeks after the last dose of study drug among participants completing combination treatment with HCV RNA levels < LLOQ at the end of treatment. | From the end of treatment through 12 weeks after the last dose of combination study drug | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Hepatitis C, Cirrhosis, Child Pugh A, Hepatitis C virus, Compensated Cirrhosis, Hepatitis C Genotype 1, Hepatitis C, Interferon-Free, Cirrhotic