Hepatitis C Virus (HCV)
Conditions
Keywords
Hepatitis C Virus (HCV), Glecaprevir, Pibrentasvir, Treatment Naïve, Cirrhosis, Compensated Cirrhosis, Genotype (GT) 1-6, Pangenotypic, Chronic Hepatitis C Virus (HCV)
Brief summary
A Phase 3b, single arm, open-label, multicenter study in treatment naïve adults with chronic HCV infection and compensated cirrhosis to assess the safety of 8 weeks of treatment with glecaprevir/pibrentasvir and to demonstrate the efficacy of the sustained virologic response 12 weeks post dosing (SVR12) rates of 8 weeks of treatment with glecaprevir/pibrentasvir compared to the historical SVR12 rates of 12 weeks of treatment with glecaprevir/pibrentasvir.
Interventions
Tablet
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
* Screening laboratory result indicating Hepatitis C Virus (HCV) Genotype (GT) 1-6 infection. * Positive plasma HCV antibody and HCV RNA viral load greater than or equal to 1000 IU/mL at Screening. * Treatment-naive to any approved or investigational anti-HCV medication. * Participant must be documented as cirrhotic, with a Child-Pugh score of less than or equal to 6.
Exclusion criteria
* Female participant who is pregnant, breastfeeding or is considering becoming pregnant during the study, or for approximately 30 days after the last dose of study drug. * Any current or historical clinical evidence of decompensated cirrhosis. * Positive test result at Screening for hepatitis B surface antigen (HBsAg), HBV deoxyribonucleic acid \> lower limit of quantification (LLOQ) in subjects with isolated positive antibody to hepatitis B core antigen (anti-HBc) (i.e., negative HBsAg and anti-hepatitis B),or anti human immunodeficiency virus antibody (HIV Ab). * HCV genotype performed by the central laboratory during screening indicating co-infection with more than one HCV genotype. * History of suspected or confirmed hepatocellular carcinoma.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) in Hepatitis C Virus (HCV) Genotype (GT) 1,2,4,5 and 6-infected Participants in the Per Protocol (PP) Population | 12 weeks after last dose of study drug | 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. Efficacy of the 8-week treatment duration compared to the historical 12-week treatment duration was demonstrated if the lower bound of the 2-sided 95% confidence interval (CI) for the percentage of participants with HCV GT1, GT2, GT4, GT5, or GT6 infection in the 8 week treatment duration achieving SVR12 was greater than 94% in the PP population. Efficacy analyses were performed following a fixed-sequence testing procedure to control the type I error rate. The percentage of participants achieving SVR12 was summarized with a 2-sided 95% CI, calculated using the normal approximation to the binomial distribution. If the number of participants who failed to achieve SVR12 rate was less than 5, the Wilson's score method was used to calculate the CI. |
| Percentage of Participants With SVR12 in HCV GT 1,2,4,5 and 6-infected Participants in the Intent-To-Treat (ITT) Population | 12 weeks after last dose of study drug | SVR12 was defined as HCV RNA level less than the LLOQ (less than 15 IU/mL) 12 weeks after the last dose of study drug. Efficacy of the 8-week treatment duration compared to the historical 12-week treatment duration was demonstrated if the lower bound of the 2-sided 95% CI for the percentage of participants with HCV GT1, GT2, GT4, GT5, or GT6 infection in the 8 week treatment duration achieving SVR12 was greater than 93% in the ITT population. Primary efficacy analyses were performed following a fixed-sequence testing procedure to control the type I error rate. The percentage of participants achieving SVR12 was summarized with a 2-sided 95% CI, calculated using the normal approximation to the binomial distribution. If the number of participants who failed to achieve SVR12 rate was less than 5, the Wilson's score method was used to calculate the CI. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With On-treatment Virologic Failure in the ITT Population | 8 weeks on treatment | On-treatment virologic failure was defined as confirmed HCV RNA ≥ 100 IU/mL after HCV RNA \< LLOQ during treatment; confirmed increase of \> 1 log(subscript)10(subscript) IU/mL above the lowest value post-baseline in HCV RNA during treatment; or HCV RNA ≥ LLOQ at end of treatment with at least 6 weeks of treatment. |
| Percentage of Participants With Post-treatment Relapse | Up to 12 weeks after the last dose of study drug | 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 as planned (defined as study drug duration ≥ 52 days for participants assigned to 8 weeks of treatment) and with HCV RNA levels \< LLOQ at the end of treatment excluding participants who had been reinfected. |
| Percentage of Participants With SVR12 in HCV GT1-6-infected Participants in the PP Population | 12 weeks after last dose of study drug | SVR12 was defined as HCV RNA level less than the LLOQ (less than 15 IU/mL) 12 weeks after the last dose of study drug. Efficacy of the 8-week treatment duration compared to the historical 12-week treatment duration was demonstrated if the lower bound of the 2-sided 95% CI for the percentage of participants with HCV GT1, GT2, GT3, GT4, GT5, or GT6 infection in the 8 week treatment duration achieving SVR12 was greater than 94% in the PP population. These efficacy analyses were performed only if success was demonstrated for both primary efficacy analyses, following a fixed-sequence testing procedure. |
| Percentage of HCV GT3-infected Participants Who Achieved SVR12 in the ITT Population | 12 weeks after the last dose of study drug | SVR12 was defined as HCV RNA level less than the LLOQ (less than 15 IU/mL) 12 weeks after the last dose of study drug. |
| Percentage of HCV GT3-infected Participants Who Achieved SVR12 in the PP Population | 12 weeks after the last dose of study drug | SVR12 was defined as HCV RNA level less than the LLOQ (less than 15 IU/mL) 12 weeks after the last dose of study drug. |
| Percentage of Participants With SVR12 in HCV GT1-6-infected Participants in the ITT Population | 12 weeks after the last dose of study drug | SVR12 was defined as HCV RNA level less than the LLOQ (less than 15 IU/mL) 12 weeks after the last dose of study drug. Efficacy of the 8-week treatment duration compared to the historical 12-week treatment duration was demonstrated if the lower bound of the 2-sided 95% CI for the percentage of participants with HCV GT1, GT2, GT3, GT4, GT5, or GT6 infection in the 8 week treatment duration achieving SVR12 was greater than 93% in the ITT population. These efficacy analyses were performed only if success was demonstrated for both primary efficacy analyses, following a fixed-sequence testing procedure. |
Countries
Bulgaria, Canada, Czechia, France, Greece, Hungary, Ireland, Israel, Italy, Poland, Portugal, Puerto Rico, Romania, Russia, Spain, Taiwan, United Kingdom, United States, Vietnam
Participant flow
Pre-assignment details
A total of 343 participants were enrolled and received ≥ 1 dose of study drug.
Participants by arm
| Arm | Count |
|---|---|
| Glecaprevir (GLE)/Pibrentasvir (PIB) for 8 Weeks GLE/PIB 300 mg/120 mg once daily (QD) for 8 weeks. | 343 |
| Total | 343 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Lost to Follow-up | 8 |
| Overall Study | Other | 1 |
| Overall Study | Withdrew Consent | 2 |
Baseline characteristics
| Characteristic | Glecaprevir (GLE)/Pibrentasvir (PIB) for 8 Weeks |
|---|---|
| Age, Continuous | 57.61 years STANDARD_DEVIATION 10.58 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 43 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 300 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 28 Participants |
| Race (NIH/OMB) Black or African American | 28 Participants |
| Race (NIH/OMB) More than one race | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 285 Participants |
| Sex: Female, Male Female | 126 Participants |
| Sex: Female, Male Male | 217 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 343 |
| other Total, other adverse events | 82 / 343 |
| serious Total, serious adverse events | 6 / 343 |
Outcome results
Primary
Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) in Hepatitis C Virus (HCV) Genotype (GT) 1,2,4,5 and 6-infected Participants in the Per Protocol (PP) Population
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. Efficacy of the 8-week treatment duration compared to the historical 12-week treatment duration was demonstrated if the lower bound of the 2-sided 95% confidence interval (CI) for the percentage of participants with HCV GT1, GT2, GT4, GT5, or GT6 infection in the 8 week treatment duration achieving SVR12 was greater than 94% in the PP population. Efficacy analyses were performed following a fixed-sequence testing procedure to control the type I error rate. The percentage of participants achieving SVR12 was summarized with a 2-sided 95% CI, calculated using the normal approximation to the binomial distribution. If the number of participants who failed to achieve SVR12 rate was less than 5, the Wilson's score method was used to calculate the CI.
Time frame: 12 weeks after last dose of study drug
Population: Per Protocol (PP) Population: All participants who received at least one dose of study drug, with the exception of participants who experienced breakthrough, or prematurely discontinued treatment prior to Week 8, or had no HCV RNA value in the SVR12 visit window or later.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Glecaprevir (GLE)/Pibrentasvir (PIB) for 8 Weeks | Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) in Hepatitis C Virus (HCV) Genotype (GT) 1,2,4,5 and 6-infected Participants in the Per Protocol (PP) Population | 100 percentage of participants |
Primary
Percentage of Participants With SVR12 in HCV GT 1,2,4,5 and 6-infected Participants in the Intent-To-Treat (ITT) Population
SVR12 was defined as HCV RNA level less than the LLOQ (less than 15 IU/mL) 12 weeks after the last dose of study drug. Efficacy of the 8-week treatment duration compared to the historical 12-week treatment duration was demonstrated if the lower bound of the 2-sided 95% CI for the percentage of participants with HCV GT1, GT2, GT4, GT5, or GT6 infection in the 8 week treatment duration achieving SVR12 was greater than 93% in the ITT population. Primary efficacy analyses were performed following a fixed-sequence testing procedure to control the type I error rate. The percentage of participants achieving SVR12 was summarized with a 2-sided 95% CI, calculated using the normal approximation to the binomial distribution. If the number of participants who failed to achieve SVR12 rate was less than 5, the Wilson's score method was used to calculate the CI.
Time frame: 12 weeks after last dose of study drug
Population: Intent to treat (ITT) population: Participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Glecaprevir (GLE)/Pibrentasvir (PIB) for 8 Weeks | Percentage of Participants With SVR12 in HCV GT 1,2,4,5 and 6-infected Participants in the Intent-To-Treat (ITT) Population | 98.2 percentage of participants |
Secondary
Percentage of HCV GT3-infected Participants Who Achieved SVR12 in the ITT Population
SVR12 was defined as HCV RNA level less than the LLOQ (less than 15 IU/mL) 12 weeks after the last dose of study drug.
Time frame: 12 weeks after the last dose of study drug
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Glecaprevir (GLE)/Pibrentasvir (PIB) for 8 Weeks | Percentage of HCV GT3-infected Participants Who Achieved SVR12 in the ITT Population | 95.2 percentage of participants |
Secondary
Percentage of HCV GT3-infected Participants Who Achieved SVR12 in the PP Population
SVR12 was defined as HCV RNA level less than the LLOQ (less than 15 IU/mL) 12 weeks after the last dose of study drug.
Time frame: 12 weeks after the last dose of study drug
Population: PP population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Glecaprevir (GLE)/Pibrentasvir (PIB) for 8 Weeks | Percentage of HCV GT3-infected Participants Who Achieved SVR12 in the PP Population | 98.4 percentage of participants |
Secondary
Percentage of Participants With On-treatment Virologic Failure in the ITT Population
On-treatment virologic failure was defined as confirmed HCV RNA ≥ 100 IU/mL after HCV RNA \< LLOQ during treatment; confirmed increase of \> 1 log(subscript)10(subscript) IU/mL above the lowest value post-baseline in HCV RNA during treatment; or HCV RNA ≥ LLOQ at end of treatment with at least 6 weeks of treatment.
Time frame: 8 weeks on treatment
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Glecaprevir (GLE)/Pibrentasvir (PIB) for 8 Weeks | Percentage of Participants With On-treatment Virologic Failure in the ITT Population | 0 percentage of participants |
Secondary
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 as planned (defined as study drug duration ≥ 52 days for participants assigned to 8 weeks of treatment) and with HCV RNA levels \< LLOQ at the end of treatment excluding participants who had been reinfected.
Time frame: Up to 12 weeks after the last dose of study drug
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Glecaprevir (GLE)/Pibrentasvir (PIB) for 8 Weeks | Percentage of Participants With Post-treatment Relapse | 0.3 percentage of participants |
Secondary
Percentage of Participants With SVR12 in HCV GT1-6-infected Participants in the ITT Population
SVR12 was defined as HCV RNA level less than the LLOQ (less than 15 IU/mL) 12 weeks after the last dose of study drug. Efficacy of the 8-week treatment duration compared to the historical 12-week treatment duration was demonstrated if the lower bound of the 2-sided 95% CI for the percentage of participants with HCV GT1, GT2, GT3, GT4, GT5, or GT6 infection in the 8 week treatment duration achieving SVR12 was greater than 93% in the ITT population. These efficacy analyses were performed only if success was demonstrated for both primary efficacy analyses, following a fixed-sequence testing procedure.
Time frame: 12 weeks after the last dose of study drug
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Glecaprevir (GLE)/Pibrentasvir (PIB) for 8 Weeks | Percentage of Participants With SVR12 in HCV GT1-6-infected Participants in the ITT Population | 97.7 percentage of participants |
Secondary
Percentage of Participants With SVR12 in HCV GT1-6-infected Participants in the PP Population
SVR12 was defined as HCV RNA level less than the LLOQ (less than 15 IU/mL) 12 weeks after the last dose of study drug. Efficacy of the 8-week treatment duration compared to the historical 12-week treatment duration was demonstrated if the lower bound of the 2-sided 95% CI for the percentage of participants with HCV GT1, GT2, GT3, GT4, GT5, or GT6 infection in the 8 week treatment duration achieving SVR12 was greater than 94% in the PP population. These efficacy analyses were performed only if success was demonstrated for both primary efficacy analyses, following a fixed-sequence testing procedure.
Time frame: 12 weeks after last dose of study drug
Population: PP population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Glecaprevir (GLE)/Pibrentasvir (PIB) for 8 Weeks | Percentage of Participants With SVR12 in HCV GT1-6-infected Participants in the PP Population | 99.7 percentage of participants |