Efficacy and Safety of Glecaprevir/Pibrentasvir (ABT-493/ABT-530) in Treatment-Naive and Treatment-Experienced Asian Adults With Chronic Hepatitis C Virus Genotype (GT) 1 to GT6 Infection With Compensated Cirrhosis and With or Without Human Immunodeficiency Virus Co-Infection

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

Official Title
-----------------
An Open-Label Study to Evaluate the Efficacy and Safety of ABT-493/ABT-530 in Treatment-Naïve and Treatment-Experienced Asian Adults With Chronic Hepatitis C Virus Genotype (GT) 1 to GT6 Infection With Compensated Cirrhosis and With or Without Human Immunodeficiency Virus Co-Infection

Conditions
-----------------
Hepatitis C Virus (HCV)

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


Participation Criteria
=================
Eligibility Criteria
-----------------
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) greater than or equal to 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 (RBV) OR sofosbuvir with RBV with or without IFN. Previous treatment must have been completed >= 8 weeks prior to screening. Compensated cirrhosis defined as Child-Pugh score of ≤ 6 at Screening and no current or past clinical evidence of Child-Pugh B or C Classification or clinical history of liver decompensation including ascites noted on physical exam, bleeding varices, use of diuretics for ascites, or hepatic encephalopathy. Absence of hepatocellular carcinoma (HCC) 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+ % >= 29%), or 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
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Glecaprevir/Pibrentasvir<br>Participants received oral glecaprevir/pibrentasvir 300 mg/120 mg once daily (QD) for 12 or 16 weeks. Participants received treatment for 12 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™;|

What is the study measuring?
-----------------
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; 15 IU/mL) 12 weeks after the last dose of study drug. | 12 weeks after the last actual dose of study drug, Week 24 or Week 28 depending on the treatment regimen. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants 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. | 12 or 16 weeks depending on the treatment regimen | 
| Percentage of Participants 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 (Week 12 or 16) through 12 weeks after the last dose of study drug (Weeks 24 or 28 depending on the treatment regimen). | 
| Percentage of HCV/HIV Co-infected Participants Achieving SVR12 | SVR12 was defined as plasma HCV RNA level less than LLOQ (15 IU/mL) 12 weeks after the last dose of study drug. | 12 weeks after the last actual dose of study drug, Week 24 or Week 28 depending on the treatment regimen | 

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