Hepatitis C Virus (HCV)
Conditions
Keywords
Chronic Hepatitis C Virus (HCV), Genotype 1 to 6, Cirrhosis, Compensated Cirrhosis, Human Immunodeficiency Virus, co-infection, Treatment-naïve, treatment-experienced, interferon, Asian
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.
Interventions
Coformulated tablet for oral administration
Sponsors
AbbVie
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) | 12 weeks after the last actual dose of study drug, Week 24 or Week 28 depending on the treatment regimen. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With On-treatment Virologic Failure | 12 or 16 weeks depending on the treatment regimen | 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. |
| Percentage of Participants With Post-treatment Relapse | 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). | 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. |
| Percentage of HCV/HIV Co-infected Participants Achieving SVR12 | 12 weeks after the last actual dose of study drug, Week 24 or Week 28 depending on the treatment regimen | SVR12 was defined as plasma HCV RNA level less than LLOQ (15 IU/mL) 12 weeks after the last dose of study drug. |
Countries
China, South Korea
Participant flow
Recruitment details
The study was conducted at 34 sites in China and South Korea. Eligible participants were chronic hepatitis C (HCV) genotype (GT)1-6-infected adults with compensated cirrhosis with or without HIV co-infection who were HCV treatment-naïve or treatment-experienced with regimens containing interferon (IFN), pegylated IFN, ribavirin, and/or sofosbuvir.
Participants by arm
| Arm | Count |
|---|---|
| Glecaprevir/Pibrentasvir 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. | 160 |
| Total | 160 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Other | 1 |
Baseline characteristics
| Characteristic | Glecaprevir/Pibrentasvir |
|---|---|
| Age, Continuous | 57.83 years STANDARD_DEVIATION 11.27 |
| Age, Customized < 65 years | 120 Participants |
| Age, Customized ≥ 65 years | 40 Participants |
| HCV Genotype Genotype 1 | 85 Participants |
| HCV Genotype Genotype 2 | 53 Participants |
| HCV Genotype Genotype 3 | 14 Participants |
| HCV Genotype Genotype 4 | 1 Participants |
| HCV Genotype Genotype 5 | 0 Participants |
| HCV Genotype Genotype 6 | 7 Participants |
| HCV Ribonucleic Acid (RNA) Level | 6.16 log₁₀ IU/mL STANDARD_DEVIATION 0.74 |
| Human Immunodeficiency Virus (HIV) Co-infection Status HCV / HIV co-infection | 0 Participants |
| Human Immunodeficiency Virus (HIV) Co-infection Status Hepatitis C infection only | 160 Participants |
| Prior HCV Treatment History Treatment-experienced | 50 Participants |
| Prior HCV Treatment History Treatment-naive | 110 Participants |
| Race/Ethnicity, Customized Asian | 160 Participants |
| Region of Enrollment China | 123 Participants |
| Region of Enrollment South Korea | 37 Participants |
| Sex: Female, Male Female | 80 Participants |
| Sex: Female, Male Male | 80 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 160 |
| other Total, other adverse events | 29 / 160 |
| serious Total, serious adverse events | 5 / 160 |
Outcome results
Primary
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.
Time frame: 12 weeks after the last actual dose of study drug, Week 24 or Week 28 depending on the treatment regimen.
Population: All enrolled participants who received at least 1 dose of study drug. Backward imputation, where applicable, was used to impute missing data. Participants with missing data after backward imputation were counted as non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Glecaprevir/Pibrentasvir | Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) | 99.4 percentage of participants |
Secondary
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.
Time frame: 12 weeks after the last actual dose of study drug, Week 24 or Week 28 depending on the treatment regimen
Population: No HCV-HIV co-infected participants were enrolled in the study
Secondary
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.
Time frame: 12 or 16 weeks depending on the treatment regimen
Population: All enrolled participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Glecaprevir/Pibrentasvir | Percentage of Participants With On-treatment Virologic Failure | 0.0 percentage of participants |
Secondary
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.
Time frame: 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).
Population: All enrolled participants who received at least one dose of study drug, with HCV RNA \< 15 IU/mL at the end of treatment, at least one post-treatment HCV RNA value, and who completed the assigned treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Glecaprevir/Pibrentasvir | Percentage of Participants With Post-treatment Relapse | 0.6 percentage of participants |