A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of ABT-493 and ABT-530 With and Without Ribavirin in Adults With HCV Who Failed a Prior DAA Containing Therapy

Study Overview
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Brief Summary
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The purpose of this study is to assess the efficacy and safety of ABT-493 and ABT-530 with or without ribavirin (RBV) in participants with chronic hepatitis C virus, (HCV)-infection who previously failed treatment with a direct acting antiviral (DAA)-containing regimen.

Official Title
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A Randomized, Open-Label, Multicenter Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Co-Administration of ABT-493 and ABT-530 (or ABT-493/ABT-530) With and Without Ribavirin in Adults With Chronic Hepatitis C Virus (HCV) Infection Who Failed a Prior Direct-Acting Antiviral Agent (DAA)-Containing Therapy

Conditions
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HCV, Chronic Hepatitis C, Hepatitis C Virus, Direct-Acting Antiviral Agent (DAA)-Experienced

Intervention / Treatment
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* Drug: ABT-493, ABT-530
* Drug: ribavirin (RBV)
* Drug: ABT-493/ABT-530


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients from 18 to 70 years in Arms A, B, and C; patients 18 years of age or older in Arms D and E. Previous treatment with DAA-containing regimen for chronic hepatitis C virus (HCV) infection resulting in either on-treatment virologic failure or post-treatment relapse Chronic HCV genotype (GT) 1, 4, 5, or 6-infection (GT4-6 in Arms D and E) Exclusion Criteria: History of severe, life-threatening or other significant sensitivity to any drug Female who is pregnant, planning to become pregnant during the study or breastfeeding; or male whose partner is pregnant or planning to become pregnant during the study Recent (within 6 months prior to study drug administration) history of drug or alcohol abuse that could preclude adherence to the protocol Positive for hepatitis B surface antigen (HBsAg) or anti-human immunodeficiency virus antibody (HIV Ab) Co-infection with more than one HCV genotype

Ages Eligible for Study
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Minimum Age: 18 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 A<br>ABT-493 (200 mg) once daily (QD) co-administered with ABT-530 (80 mg) QD for 12 weeks in chronic HCV genotype 1- infected participants without cirrhosis. | Drug: ABT-493, ABT-530<br>* ABT-493 (tablet) dosed with ABT-530 (tablet)<br>* Other names: ABT-493/ABT-530 (ABT-493 coformulated with ABT-267) also known as MAVYRET;|
| Experimental: Arm B<br>ABT-493 (300 mg) once daily (QD) co-administered with ABT-530 (120 mg) QD plus ribavirin (RBV) for 12 weeks in chronic HCV genotype 1- infected participants without cirrhosis. | Drug: ABT-493, ABT-530<br>* ABT-493 (tablet) dosed with ABT-530 (tablet)<br>* Other names: ABT-493/ABT-530 (ABT-493 coformulated with ABT-267) also known as MAVYRET;Drug: ribavirin (RBV)<br>* Tablet<br>|
| Experimental: Arm C<br>ABT-493 (300 mg) once daily (QD) co-administered with ABT-530 (120 mg) QD for 12 weeks in chronic HCV genotype 1- infected participants without cirrhosis. | Drug: ABT-493, ABT-530<br>* ABT-493 (tablet) dosed with ABT-530 (tablet)<br>* Other names: ABT-493/ABT-530 (ABT-493 coformulated with ABT-267) also known as MAVYRET;|
| Experimental: Arm D<br>ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 12 weeks in HCV genotypes 1- or 4-6- infected participants with or without cirrhosis. | Drug: ABT-493/ABT-530<br>* Tablet; ABT-493 coformulated with ABT-530<br>* Other names: MAVYRET;|
| Experimental: Arm E<br>ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 16 weeks in HCV genotype 1- or 4-6- infected participants with or without cirrhosis. | Drug: ABT-493/ABT-530<br>* Tablet; ABT-493 coformulated with ABT-530<br>* Other names: MAVYRET;|

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 (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 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 4 Weeks Post-treatment (SVR4) | SVR4 was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification [<LLOQ]) 4 weeks after the last dose of study drug. | 4 weeks after the last actual dose of study drug | 
| Percentage of Participants With On-treatment Virologic Failure | On-treatment virologic failure was defined as confirmed HCV RNA ≥ 100 IU after HCV RNA < LLOQ during treatment; confirmed increase of > 1 log(subscript)10(subscript) IU/mL above the lowest value post-baseline in HCV RNA during treatment; or HCV RNA ≥ LLOQ at end of treatment with at least 6 weeks of treatment. | Day 3, Treatment Weeks 1, 2, 4, 6, 8, 10, 12 (end of treatment for 12-week treatment arms), and 16 (end of treatment for 16-week treatment arm) or premature discontinuation from treatment | 
| 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 with HCV RNA levels < LLOQ at the end of treatment, excluding reinfection. | From the end of treatment through 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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HCV Genotype 1, HCV Genotype 6, Hepatitis C, HCV GT1, Interferon (IFN) free, HCV Genotype 5, HCV, HCV GT4, HCV Genotype 4, Chronic Hepatitis C, Chronic HCV, Hepatitis C Genotype 1, HCV GT5