Hepatitis C Virus (HCV)
Conditions
Keywords
Acute HCV Infection, HCV Genotype 1-6, Hepatitis C, Glecaprevir, Pibrentasvir, Mavyret
Brief summary
HCV infection is a global health problem. HCV mainly affects liver cells and causes the liver to become inflamed and damaged. This study will evaluate how safe and effective glecaprevir/pibrentasvir (GLE/PIB) is in adult and adolescent participants with acute HCV infection. GLE/PIB is an approved drug for the treatment of chronic HCV. Around 283 participants at least 12 years of age with acute HCV Infection will be enrolled in approximately 70 sites worldwide. Participants will receive oral tablets of GLE/PIB once daily (QD) for 8 weeks and will be followed for 12 weeks after the end of treatment. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, monitoring for side effects and completing questionnaires.
Interventions
Oral tablets
Sponsors
AbbVie
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Evidence of acute HCV infection prior to enrollment, defined as a physician diagnosis of acute HCV infection, quantifiable HCV ribonucleic Acid (RNA) at screening, and at least 1 of the following: * Negative anti-HCV antibody, HCV RNA and/or HCV core antigen followed by a positive HCV RNA or HCV core antigen all within an 8-month period prior to screening; OR * Negative anti-HCV antibody, HCV RNA and/or HCV core antigen followed by a positive HCV RNA or HCV core antigen all within an 11-month period prior to screening; AND risk behavior for HCV infection within 6 months prior to positive HCV RNA or HCV core antigen; OR * Clinical signs and symptoms compatible with acute hepatitis \[alanine aminotransferase (ALT) \> 5 × upper limit of normal (ULN) and/or jaundice\] in the absence of a history of chronic liver disease or other cause of acute hepatitis and positive HCV RNA or HCV core antigen all within an 8-month period prior to screening; AND risk behavior for HCV infection within 6 months prior to positive HCV RNA or HCV core antigen; OR * Negative anti-HCV antibody with a positive HCV RNA or HCV core antigen within a 5-month period prior to screening. * Absence of hepatocellular carcinoma (HCC), for participants with cirrhosis, or with indeterminate cirrhosis status, as indicated by a negative ultrasound, computed tomography (CT) scan or magnetic resonance imaging (MRI) within 3 months prior to screening or a negative ultrasound at screening. Participant who has a positive ultrasound result suspicious of HCC followed by a subsequent negative CT scan or MRI or biopsy result will be eligible for the study. * Participants documented as having no cirrhosis or as having compensated cirrhosis.
Exclusion criteria
* Participants with prior treatment, including interferon for this HCV infection. * History of liver decompensation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Sustained Virologic Response 12 Weeks Post-treatment (SVR12) in the Intention-to-Treat (ITT) Population | 12 weeks after last dose of study treatment (Week 20) | SVR12 is defined as the hepatitis C virus (HCV) ribonucleic acid (RNA) level less than the lower limit of quantification (\< LLOQ) 12 weeks after the last dose of study treatment. Efficacy was demonstrated if the lower bound of the 2-sided 95% CI for the percentage of participants achieving SVR12 was greater than 90.5%. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving SVR12 in the Modified ITT-Virologic Failure (mITT-VF) Population | 12 weeks after last dose of study treatment (Week 20) | SVR12 is defined as the HCV RNA level \< LLOQ 12 weeks after the last dose of study treatment. Efficacy was demonstrated if the lower bound of the 2-sided 95% CI for the percentage of participants achieving SVR12 was greater than 92.7%. This efficacy analysis was performed only if success was demonstrated for the primary efficacy analysis, following a fixed-sequence testing procedure. |
| Percentage of Participants With On-Treatment Virologic Failure in the ITT Population | Up to Week 8 | On-treatment virologic failure is defined as confirmed increase in HCV RNA of \> 1 log\^10 IU/mL above the lowest post-baseline value during treatment, confirmed HCV RNA \>= 100 IU/mL after HCV RNA \< LLOQ during treatment, or HCV RNA \>= LLOQ at the end of treatment (EOT) with at least 6 weeks of treatment. |
| Percentage of Participants With Post-Treatment (PT) Relapse in the ITT Population | Up to 12 weeks after the last dose of study treatment (Week 20) | PT relapse is defined as confirmed HCV RNA \>= LLOQ between the EOT and 12 weeks after the last dose of study treatment among participants who completed treatment as planned (study treatment duration \>= 52 days) with HCV RNA \< LLOQ at the EOT and with at least 1 PT HCV RNA value, excluding cases of reinfection. |
| Percentage of Participants With PT Reinfection With HCV in the ITT Population | Up to 12 weeks after the last dose of study treatment (Week 20) | PT reinfection is defined as confirmed HCV RNA \>= LLOQ in the PT period in a participant who had HCV RNA \< LLOQ at the final treatment visit, along with the PT detection of a different HCV genotype, subtype, or clade compared with baseline. |
Countries
Australia, Austria, Canada, France, Germany, Italy, Spain, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Glecaprevir/Pibrentasvir Participants treated QD with glecaprevir/pibrentasvir 300 mg/120 mg for 8 weeks. | 286 |
| Total | 286 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 6 |
| Overall Study | Other, Not Specified | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Glecaprevir/Pibrentasvir |
|---|---|
| Age, Continuous | 43.7 years STANDARD_DEVIATION 11.71 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 76 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 210 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race/Ethnicity, Customized Asian | 7 Participants |
| Race/Ethnicity, Customized Black or African American | 30 Participants |
| Race/Ethnicity, Customized Multiple | 3 Participants |
| Race/Ethnicity, Customized White | 246 Participants |
| Sex: Female, Male Female | 31 Participants |
| Sex: Female, Male Male | 255 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 286 |
| other Total, other adverse events | 49 / 286 |
| serious Total, serious adverse events | 12 / 286 |
Outcome results
Primary
Percentage of Participants Achieving Sustained Virologic Response 12 Weeks Post-treatment (SVR12) in the Intention-to-Treat (ITT) Population
SVR12 is defined as the hepatitis C virus (HCV) ribonucleic acid (RNA) level less than the lower limit of quantification (\< LLOQ) 12 weeks after the last dose of study treatment. Efficacy was demonstrated if the lower bound of the 2-sided 95% CI for the percentage of participants achieving SVR12 was greater than 90.5%.
Time frame: 12 weeks after last dose of study treatment (Week 20)
Population: ITT Population: all enrolled participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Glecaprevir/Pibrentasvir | Percentage of Participants Achieving Sustained Virologic Response 12 Weeks Post-treatment (SVR12) in the Intention-to-Treat (ITT) Population | 96.2 percentage of participants |
Secondary
Percentage of Participants Achieving SVR12 in the Modified ITT-Virologic Failure (mITT-VF) Population
SVR12 is defined as the HCV RNA level \< LLOQ 12 weeks after the last dose of study treatment. Efficacy was demonstrated if the lower bound of the 2-sided 95% CI for the percentage of participants achieving SVR12 was greater than 92.7%. This efficacy analysis was performed only if success was demonstrated for the primary efficacy analysis, following a fixed-sequence testing procedure.
Time frame: 12 weeks after last dose of study treatment (Week 20)
Population: mITT-VF population: all enrolled participants who received at least one dose of study treatment, excluding those who did not achieve SVR12 for reasons other than virologic failure (i.e., those with HCV reinfection, those who did not achieve SVR12 due to early premature discontinuation of study treatment, and those who were missing HCV RNA data in the SVR12 window after backward imputation).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Glecaprevir/Pibrentasvir | Percentage of Participants Achieving SVR12 in the Modified ITT-Virologic Failure (mITT-VF) Population | 100 percentage of participants |
Secondary
Percentage of Participants With On-Treatment Virologic Failure in the ITT Population
On-treatment virologic failure is defined as confirmed increase in HCV RNA of \> 1 log\^10 IU/mL above the lowest post-baseline value during treatment, confirmed HCV RNA \>= 100 IU/mL after HCV RNA \< LLOQ during treatment, or HCV RNA \>= LLOQ at the end of treatment (EOT) with at least 6 weeks of treatment.
Time frame: Up to Week 8
Population: ITT Population: all enrolled participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Glecaprevir/Pibrentasvir | Percentage of Participants With On-Treatment Virologic Failure in the ITT Population | 0 percentage of participants |
Secondary
Percentage of Participants With Post-Treatment (PT) Relapse in the ITT Population
PT relapse is defined as confirmed HCV RNA \>= LLOQ between the EOT and 12 weeks after the last dose of study treatment among participants who completed treatment as planned (study treatment duration \>= 52 days) with HCV RNA \< LLOQ at the EOT and with at least 1 PT HCV RNA value, excluding cases of reinfection.
Time frame: Up to 12 weeks after the last dose of study treatment (Week 20)
Population: ITT Population: all enrolled participants who received at least 1 dose of study treatment. Participants who completed treatment as planned with HCV RNA \< LLOQ at the EOT and with at least 1 PT HCV RNA value.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Glecaprevir/Pibrentasvir | Percentage of Participants With Post-Treatment (PT) Relapse in the ITT Population | 0 percentage of participants |
Secondary
Percentage of Participants With PT Reinfection With HCV in the ITT Population
PT reinfection is defined as confirmed HCV RNA \>= LLOQ in the PT period in a participant who had HCV RNA \< LLOQ at the final treatment visit, along with the PT detection of a different HCV genotype, subtype, or clade compared with baseline.
Time frame: Up to 12 weeks after the last dose of study treatment (Week 20)
Population: ITT Population: all enrolled participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Glecaprevir/Pibrentasvir | Percentage of Participants With PT Reinfection With HCV in the ITT Population | 0.7 percentage of participants |