A Study to Evaluate the Efficacy and Safety of Glecaprevir/Pibrentasvir (ABT-493/ABT-530) in Treatment-Naive and Treatment-Experienced, Non-Cirrhotic Asian Adults With Chronic Hepatitis C Virus Genotype (GT) 1 to GT6 Infection With or Without Human Immunodeficiency Virus Co-Infection

Study Overview
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Brief Summary
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This study will evaluate the efficacy and safety of glecaprevir/pibrentasvir (ABT-493/ABT-530) in non-cirrhotic chronic hepatitis C virus (HCV) genotype (GT)1 to GT6-infected Asian participants with or without human immunodeficiency virus (HIV) co-infection who are HCV treatment-naïve or treatment-experienced with interferon (IFN) with or without ribavirin (RBV), OR sofosbuvir with RBV with or without IFN.

Detailed Description
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Randomization was stratified by geographic region (China, South Korea, Singapore), genotype (GT1, GT2, combined GT3 - 6), and HCV/HIV co-infection status (co-infected, not co-infected). In China, eligible participants were randomized to Arm A or Arm B (defined below) in the following ratios: 2:1 for GT1, 2:1 for GT2, and 2:1 for combined GT3-6. In South Korea and Singapore, eligible participants were randomized to Arm A or Arm B in the following ratios: 2:1 for GT1 and 2:1 for GT2. All Primary and Secondary Outcome Measures were pre-specified to be analyzed only in Arm A.

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 Treatment-Naïve and Treatment-Experienced, Non-Cirrhotic Asian Adults With Chronic Hepatitis C Virus Genotype (GT) 1 to GT6 Infection With or Without Human Immunodeficiency Virus Co-Infection

Conditions
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Hepatitis C Virus (HCV)

Intervention / Treatment
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* Drug: Placebo
* Drug: Glecaprevir/Pibrentasvir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must be of Asian descent Screening laboratory result indicating hepatitis C virus (HCV) genotype (GT) 1, 2, 3, 4, 5 or 6 infection. Positive anti-HCV antibody (Ab) and HCV ribonucleic acid (RNA) viral load ≥ 1000 IU/ mL at Screening Visit. Chronic HCV infection defined as one of the following: Positive for anti-HCV Ab or HCV RNA at least 6 months before Screening; or A liver biopsy consistent with chronic HCV infection HCV treatment-naïve to any approved or investigational HCV treatment or treatment-experienced with interferon (IFN) (alpha, beta or pegylated interferon[pegIFN] with or without ribavirin, OR sofosbuvir with RBV with or without IFN. Previous treatment must have been completed ≥ 8 weeks prior to screening. Participant must be documented as non-cirrhotic. Participants enrolled with human immunodeficiency virus (HIV)-1 and HCV co-infection must also meet the following criteria: Positive test result for human immunodeficiency virus antibody (HIV Ab) at Screening Naïve to treatment with any antiretroviral therapy (ART) with a cluster of differentiation (CD)4+ count greater than or equal to 500 cells/mm³ (or CD4+ percent ≥ 29%) On a stable, qualifying HIV-1 ART regimen with CD4+ count ≥ 200 cells/mm³ (or CD4+ % ≥ 14%) at Screening and plasma HIV-1 RNA below lower limit of quantification (LLOQ) by an approved plasma HIV-1 RNA quantitative assay at Screening and at least once during the 12 months prior to Screening. Exclusion Criteria: Positive test result for Hepatitis B surface antigen (HbsAg) or positive test result for hepatitis B virus (HBV) deoxyribonucleic acid (DNA) if HBsAg is negative. Any cause of liver disease other than chronic HCV-infection. HCV genotype performed during screening indicating co-infection with more than one HCV genotype Clinically significant abnormalities, other than HCV infection or HCV/HIV co-infection Chronic human immunodeficiency virus, type 2 (HIV-2) infection Additional Exclusion Criteria for participants with HCV/HIV Co-Infection: For participants on stable ART, taking anti-retroviral agent(s) other than those permitted Treatment for an acquired immunodeficiency syndrome (AIDS)-associated opportunistic infection within 12 months of Screening or prophylaxis for an AIDS-associated opportunistic infection within 6 months of screening Diagnosis of any clinical AIDS-defining event within 12 months prior to Screening.

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Glecaprevir/Pibrentasvir<br>Participants received oral glecaprevir/pibrentasvir (300 mg/120 mg) once daily with food for 8 or 16 weeks during the double-blind (DB) treatment period. Participants received treatment for 8 weeks with the exception of treatment-experienced, genotype 3-infected participants who received treatment for 16 weeks. | Drug: Glecaprevir/Pibrentasvir<br>* Coformulated tablet for oral administration<br>* Other names: MAVYRET™;|
| Experimental: Placebo / Glecaprevir/Pibrentasvir<br>Participants received placebo to glecaprevir/pibrentasvir for 8 or 16 weeks during the DB treatment period followed by glecaprevir/pibrentasvir (300 mg/120 mg) once daily for 8 or 16 weeks during the open-label (OL) treatment period. In each period participants received treatment for 8 weeks with the exception of treatment-experienced, genotype 3-infected participants who received treatment for 16 weeks. | Drug: Placebo<br>* Matching placebo tablet for oral administration<br>Drug: Glecaprevir/Pibrentasvir<br>* Coformulated tablet for oral administration<br>* Other names: MAVYRET™;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of HCV GT1 - GT6-Infected Participants in Arm A Who Achieved Sustained Virologic Response 12 Weeks Post Treatment (SVR12) | Sustained virologic response 12 weeks post-treatment (SVR12) was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification (LLOQ; less than 15 IU/mL) 12 weeks after the last dose of study drug. | 12 weeks after the last actual dose of study drug, Week 20 or Week 28 depending on the treatment regimen. | 
| Percentage of HCV GT1-Infected Participants in Arm A Who Achieved SVR12 | SVR12 was defined as plasma HCV RNA level less than 15 IU/mL 12 weeks after the last dose of study drug. | 12 weeks after last actual dose of study drug, Week 20 or Week 28 depending on the treatment regimen | 
| Percentage of HCV GT2-Infected Participants in Arm A Who Achieved SVR12 | SVR12 was defined as plasma HCV RNA level less than 15 IU/mL 12 weeks after the last actual dose of study drug. | 12 weeks after the last dose of study drug, Week 20 or Week 28 depending on the treatment regimen. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants in Arm A With On-treatment Virologic Failure | On-treatment virologic failure was defined as meeting one of the following: confirmed increase from nadir in HCV RNA (two consecutive HCV RNA measurements > 1 log₁₀ IU/mL above nadir) at any time point during the treatment period; or confirmed HCV RNA greater than or equal to 100 IU/mL after HCV RNA < 15 IU/mL during the treatment period, or HCV RNA ≥ 15 IU/mL at end of treatment with at least 6 weeks of treatment. | 8 or 16 weeks depending on the treatment regimen | 
| Percentage of Participants in Arm A With Post-treatment Relapse | Post-treatment relapse was defined as confirmed HCV RNA greater than or equal to 15 IU/mL between the end of treatment and 12 weeks after the last dose of study drug among participants who completed treatment with HCV RNA levels < 15 IU/mL at the end of treatment, excluding re-infection. | From the end of treatment (Weeks 8 or 16) through 12 weeks after the last dose of study drug (Weeks 20 or 28 depending on the treatment regimen). | 
| Percentage of HCV/HIV Co-infected Participants in Arm A Who Achieved SVR12 | SVR12 was defined as plasma HCV RNA level less than 15 IU/mL 12 weeks after the last dose of study drug. | 12 weeks after the last actual dose of study drug, Week 20 or 28 depending on the treatment regimen | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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interferon, Treatment-experienced, Chronic Hepatitis C Virus (HCV), Genotype 1 to 6, Asian, non-cirrhotic, Human Immunodeficiency Virus, co-infection, Treatment-naïve