A Study to Evaluate the Efficacy and Safety of ABT-493/ABT-530 in Subjects With Genotype 1 Infection

Study Overview
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Brief Summary
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This study seeks to evaluate the efficacy and safety of ABT-493/ABT-530 in participants with Genotype 1 hepatitis C virus infection without cirrhosis

Official Title
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A Randomized, Open-Label, Multicenter Study to Evaluate the Efficacy and Safety of ABT-493/ABT-530 in Adults With Chronic Hepatitis C Virus Genotype 1 Infection (ENDURANCE-1)

Conditions
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HCV, Chronic Hepatitis C, Hepatitis C Virus

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, at least 18 years of age at time of screening. Screening laboratory result indicating hepatitis C virus (HCV) genotype 1 (GT1) infection. Chronic HCV infection. Subject must be HCV treatment-naïve (i.e., patient has never received a single dose of any approved or investigational regimen) or treatment-experienced (has failed prior interferon [IFN] or pegylated IFN (pegIFN) with or without ribivarin (RBV), or sofosbuvir (SOF) plus RBV with or without pegIFN therapy). Subjects must be non-cirrhotic. Additional Inclusion Criteria for HCV GT1/human immununovirus type 1 (HIV-1) co-infected patients: HIV-1 antiretroviral treatment (ART) naïve with CD4 ≥ 500 cells/mm3 (or CD4+ % ≥ 29%) at Screening and plasma HIV-1 RNA <1,000 copies/mL at Screening and at least once during the 12 months prior to Screening. OR On a stable, qualifying HIV-1 ART regimen for at least 8 weeks prior to screening, with CD4 ≥ 200 cells/mm3 (or CD4+ % ≥14%) at Screening and plasma HIV-1 RNA < LLOQ at Screening and at least once during the 12 months prior to Screening. Exclusion Criteria: History of severe, life-threatening or other significant sensitivity to any excipients 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). HCV genotype performed during screening indicating co-infection with more than one HCV genotype. Chronic HIV type 2 (HIV-2) infection.

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: ABT-493/ABT-530 for 12 weeks<br>ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 12 weeks. | Drug: ABT-493/ABT-530<br>* Tablet; ABT-493 coformulated with ABT-530<br>* Other names: MAVYRET;|
| Experimental: ABT-493/ABT-530 for 8 weeks<br>ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 8 weeks. | 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 Mono-infected Hepatitis C Virus Genotype 1 (HCV GT1), Direct-acting Antiviral Agent (DAA) Naïve Participants in the 12-Week Treatment Arm | 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. The primary efficacy endpoint was noninferiority of the percentage of participants who achieved SVR12 in the 12-week treatment group compared with the historical control rate for HCV GT1 subjects who are treatment-naïve or treated with pegylated-interferon alfa-2a or alfa-2b and ribavirin (pegIFN/RBV). | 12 weeks after the last actual dose of study drug | 
| Percentage of Participants With SVR12: Noninferiority of 8-Week Arm to 12-Week Arm in Mono-infected HCV GT1, DAA-Naïve Participants, Excluding Those Who Discontinued/Experienced Virologic Failure by Week 8 or Had No HCV RNA Value at Week 12 or Later | SVR12 was defined as plasma HCV RNA level <LLOQ 12 weeks after the last dose of study drug. The primary efficacy endpoint was noninferiority of the percentage of mono-infected HCV GT1, DAA-naïve participants (excluding those who discontinued/experienced virologic failure by Week 8 or had no HCV RNA value at Week 12 or later) who achieved SVR12 in the 8-week treatment arm compared with the 12-week treatment arm. | 12 weeks after last actual dose of study drug | 
| Percentage of Participants With SVR12: Noninferiority of 8-Week Treatment Arm to 12-Week Treatment Arm in Mono-infected HCV GT1, DAA-Naïve Participants | SVR12 was defined as plasma HCV RNA level <LLOQ 12 weeks after the last dose of study drug. The primary efficacy endpoint was noninferiority of the percentage of mono-infected HCV GT1, DAA-naïve participants who achieved SVR12 in the 8-week treatment arm compared with the 12-week treatment arm. | 12 weeks after the last actual dose of study drug | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With SVR12 in Mono-infected HCV GT1 Participants | SVR12 was defined as plasma HCV RNA level <LLOQ 12 weeks after the last dose of study drug. | 12 weeks after last actual dose of study drug | 
| Percentage of Participants With SVR12 | SVR12 was defined as plasma HCV RNA level <LLOQ 12 weeks after the last dose of study drug. | 12 weeks after last actual dose of study drug | 
| Percentage of Participants With SVR12 in Co-infected HCV GT1/Human Immunodeficiency Virus Type 1 (HIV-1) Participants | SVR12 was defined as plasma HCV RNA level <LLOQ 12 weeks after the last dose of study drug. | 12 weeks after last actual dose of study drug | 
| Percentage of Participants With SVR12 in HCV GT1-infected, Prior Sofosbuvir (SOF) Treatment-Experienced Participants | SVR12 was defined as plasma HCV RNA level <LLOQ 12 weeks after the last dose of study drug. | 12 weeks after last actual dose of study drug | 
| Percentage of Participants With On-treatment Virologic Failure | On-treatment virologic failure was defined as confirmed increase of >1 log(subscript)10(subscript) IU/mL above the lowest value 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. | Treatment Weeks 1, 2, 4, 8 (end of treatment for 8-week treatment arm), and 12 (end of treatment for 12-week treatment arm) or premature discontinuation from treatment | 
| Percentage of Participants With On-treatment Virologic Failure in Mono-infected HCV GT1, DAA-Naïve Participants | On-treatment virologic failure was defined as confirmed increase of >1 log(subscript)10(subscript) IU/mL above the lowest value 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. | Treatment Weeks 1, 2, 4, 8 (end of treatment for 8-week treatment arm), and 12 (end of treatment for 12-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 who completed treatment 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 | 
| Percentage of Participants With Post-treatment Relapse in Mono-infected HCV GT1, DAA-Naïve Participants | 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 who completed treatment 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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Without cirrhosis, Chronic Hepatitis C, Hepatitis C Genotype 1 (GT1), IFN free, Hepatitis C, Ribavirin Free, Interferon (IFN) Free, HCV, Hepatitis C virus, DAA, HCV GT1, Non-cirrhotic, RBV Free