A Study to Evaluate the Efficacy and Safety of ABT-493/ABT-530 in Adults With Chronic Hepatitis C Virus (HCV) Genotype 2 Infection

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-493/ABT-530 in adults with genotype 2 chronic hepatitis C virus (HCV) infection.

Official Title
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A Randomized, Double-Blind, Placebo-controlled, Multicenter Study to Evaluate the Efficacy and Safety of ABT-493/ABT-530 in Adults With Chronic Hepatitis C Virus Genotype 2 Infection (ENDURANCE-2)

Conditions
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Chronic Hepatitis C Virus (HCV) Infection

Intervention / Treatment
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* Drug: ABT-493/ABT-530
* Drug: Placebo for ABT-493/ABT-530


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Screening laboratory result indicating hepatitis C virus (HCV) Genotype-2 (GT2) infection. Chronic HCV infection. Subject must be HCV treatment-naïve (subject had never received a single dose of any approved or investigational regimen) or had failed prior interferon (IFN) or pegylated-interferon (pegIFN) ± ribavirin (RBV) or sofosbuvir (SOF) + RBV ± pegIFN therapy. Subject must be non-cirrhotic. Exclusion Criteria: History of severe, life-threatening or other significant sensitivity to any excipient of the study drugs. 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 in the opinion of the investigator. Positive test result at Screening for hepatitis B surface antigen (HBsAg) or anti-human immunodeficiency virus antibody (HIV Ab). HCV genotype performed during screening indicating coinfection with more than 1 HCV genotype.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 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: Arm A DB Active Drug<br>ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 12 weeks (double-blind [DB] treatment period) | Drug: ABT-493/ABT-530<br>* Tablet; ABT-493 coformulated with ABT-530<br>* Other names: MAVYRET;|
| Experimental: Arm B DB Placebo<br>Placebo for ABT-493/ABT-530 QD for 12 weeks (DB treatment period) | Drug: Placebo for ABT-493/ABT-530<br>* tablet<br>|
| Experimental: Arm B OL Active Drug<br>ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 12 weeks (open-label [OL] treatment period) | 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) in Arm A DB Active Drug Excluding Prior SOF + Ribavirin (RBV) ± pegIFN Failures: Noninferiority Analysis | 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 active study drug. The primary efficacy endpoint was the noninferiority of the percentage of participants who achieved SVR12 in Arm A Double Blind (DB) Active Drug excluding prior sofosbuvir (SOF) + ribavirin (RBV) ± pegylatedinterferon (pegIFN) failures compared with the historical control rate for patients treated with the current standard of care (SOF + RBV for 12 weeks). | 12 weeks after the last actual dose of active study drug | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With SVR12 in Arm A DB Active Drug Excluding Prior SOF + Ribavirin (RBV) ± pegIFN Failures: Superiority Analysis | SVR12 was defined as plasma HCV RNA level <LLOQ 12 weeks after the last dose of study drug. The secondary efficacy endpoint was the superiority of the percentage of participants who achieved SVR12 in Arm A Double Blind (DB) Active Drug excluding prior SOF + RBV ± pegIFN failures compared with the historical control rate for patients treated with the current standard of care (SOF + RBV for 12 weeks). As pre-specified in the study protocol, the primary outcome measure and the secondary outcome measure are not tested independently from each other. Rather, the two measures are ranked in a fixed sequential testing procedure that only if success was demonstrated for the primary outcome (i.e. non-inferiority test of Arm A SVR12 rate to the standard of care) did we test the first secondary outcome (i.e. superiority test of Arm A SVR12 rate to the standard of care). | 12 weeks after the last actual dose of active study drug | 
| Percentage of Participants With On-treatment Virologic Failure in Arm A DB Active Drug Excluding Prior SOF + Ribavirin (RBV) ± pegIFN Failures | On-treatment virologic failure was defined as confirmed increase of > 1 log(subscript)10(subscript) IU/mL above the lowest value of post-baseline HCV RNA during treatment; confirmed HCV RNA ≥ 100 IU/mL after HCV RNA < LLOQ during treatment, or HCV RNA ≥ LLOQ at end of treatment with at least 6 weeks of treatment. | Up to Week 12 post baseline | 
| Percentage of Participants With Post-treatment Relapse in Arm A DB Active Drug Excluding Prior SOF + Ribavirin (RBV) ± pegIFN Failures | Post-treatment relapse was defined as confirmed HCV RNA ≥ LLOQ between the end of DB treatment and 12 weeks after the last dose of active study drug among participants who completed treatment with HCV RNA levels < LLOQ at the end of treatment, excluding reinfection. | Between End of Treatment (Week 12) and 12 weeks after the last dose of Arm A DB active drug (up to Week 24) | 
| Percentage of Participants With SVR12 in Arm A DB Active Drug With Prior SOF + RBV ± pegIFN Failure | SVR12 was defined as HCV RNA level <LLOQ 12 weeks after the last dose of active study drug. | 12 weeks after the last actual dose of active study drug | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Treatment-Naive, Hepatitis C Virus Genotype 2, Sofosbuvir (SOF)-Experienced, Treatment-Experienced, Non-cirrhotic