Hepatitis C Virus (HCV)
Conditions
Keywords
glecaprevir, pibrentasvir, compensated cirrhosis, non-cirrhotic, interferon (IFN), pegylated interferon (pegIFN), ribavirin (RBV), sofosbuvir (SOF), Sustained Virologic Response 12 weeks post dosing (SVR12), Chronic, Genotype 5 or 6 Infection
Brief summary
A Phase 3b, open-label, multicenter study to evaluate the efficacy and safety of glecaprevir/pibrentasvir for an 8- or 12-week treatment duration in participants with chronic hepatitis C virus (HCV) genotype (GT) 5 or 6 infection, with or without compensated cirrhosis respectively.
Interventions
Fixed-dose combination tablets taken orally once a day.
Sponsors
AbbVie
Study design
Allocation
NON_RANDOMIZED
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) GT5 or 6 infection. * Participant has a positive anti-HCV antibody (Ab) and plasma HCV ribonucleic acid (RNA) greater than or equal to 1000 IU/mL at Screening Visit. * Participant must be HCV treatment-naïve (i.e., has never received a single dose of any approved or investigational anti-HCV medication) or treatment-experienced (i.e., has failed prior interferon \[IFN\] or pegylated interferon \[pegIFN\] with or without ribavirin \[RBV\], or sofosbuvir \[SOF\] plus RBV with or without pegIFN therapy). Prior HCV treatment with any other approved or investigational medications is not allowed. Previous HCV treatment must have been completed greater than or equal to 2 months prior to screening. * Participant must be documented as having no cirrhosis or compensated cirrhosis.
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. * Recent (within 6 months prior to study drug administration) history of drug or alcohol abuse that could preclude adherence to the protocol in the opinion of the investigator. * Positive test result at screening for hepatitis B surface antigen (HBsAg) or anti-human immunodeficiency virus antibody (HIV Ab). * HCV genotype performed during screening indicating co-infection with more than one HCV genotype. * History of severe, life-threatening or other significant sensitivity to any excipients of the study drug.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Sustained Virologic Response 12 Weeks Post Treatment (SVR12) | 12 weeks after last dose of study drug (week 20 or 24 depending on the treatment regimen) | SVR12 is defined as 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 actual dose of study drug. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With On-treatment HCV Virologic Failure | 8 or 12 weeks (depending on the treatment regimen) | HCV virologic failure was defined as one of the following conditions: * confirmed HCV RNA ≥ 100 IU/mL after HCV RNA \< 15 IU/mL during the Treatment Period; or 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 * HCV RNA ≥ 15 IU/mL at end of treatment with at least 6 weeks of treatment, where the HCV RNA value must be collected on or after Study Drug Day 36 and study drug duration ≥ 36 days. |
| Percentage of Participants With Relapse | End of treatment (week 8 or 12 depending on the treatment regimen) through 12 weeks after the end of treatment. | Relapse was defined as confirmed HCV RNA ≥ 15 IU/mL between the end of treatment and 12 weeks after the last dose of study drug among participants who completed treatment as planned with HCV RNA \< 15 IU/mL at the end of treatment and had post-treatment HCV RNA data; participants who had been shown to be re-infected were not considered to have relapsed. |
Countries
Australia, Belgium, Canada, France, New Zealand, Singapore, South Africa, United States, Vietnam
Participant flow
Recruitment details
This study was conducted in 24 hospitals or clinics in Europe (Belgium, France), Oceania (Australia, New Zealand), North America (Canada, USA), South Africa, and southeast Asia (Singapore, Vietnam). Participants were screened between January 17, 2017, and December 26, 2017.
Pre-assignment details
Enrolled participants with genotype 5 or 6 hepatitis C (HCV) were assigned to treatment with glecaprevir/pibrentasir for either 8 weeks or 12 weeks based on cirrhotic status.
Participants by arm
| Arm | Count |
|---|---|
| Genotype 5-infected Participants received oral glecaprevir/pibrentasir (300 mg/120 mg) once daily with food for either 8 weeks (those without cirrhosis) or 12 weeks (those with compensated cirrhosis), according to label. | 23 |
| Genotype 6-infected Participants received oral glecaprevir/pibrentasir (300 mg/120 mg) once daily with food for either 8 weeks (those without cirrhosis) or 12 weeks (those with compensated cirrhosis), according to label. | 61 |
| Total | 84 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Patient Left the Country | 0 | 1 |
Baseline characteristics
| Characteristic | Genotype 6-infected | Total | Genotype 5-infected |
|---|---|---|---|
| Age, Continuous | 54.0 years | 59.0 years | 68.0 years |
| Age, Customized < 65 years | 45 Participants | 53 Participants | 8 Participants |
| Age, Customized ≥ 65 years | 16 Participants | 31 Participants | 15 Participants |
| Cirrhosis Status Cirrhotic | 6 Participants | 9 Participants | 3 Participants |
| Cirrhosis Status Non-cirrhotic | 55 Participants | 75 Participants | 20 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 61 Participants | 84 Participants | 23 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| HCV Ribonucleic Acid (RNA) Concentration | 6.64 log10 IU/mL STANDARD_DEVIATION 0.74 | 6.61 log10 IU/mL STANDARD_DEVIATION 0.69 | 6.52 log10 IU/mL STANDARD_DEVIATION 0.53 |
| Prior HCV Treatment History Experienced | 4 Participants | 8 Participants | 4 Participants |
| Prior HCV Treatment History Naive | 57 Participants | 76 Participants | 19 Participants |
| Race/Ethnicity, Customized Asian | 56 Participants | 57 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Multi-race | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 4 Participants | 25 Participants | 21 Participants |
| Region of Enrollment Australia | 8 participants | 8 participants | 0 participants |
| Region of Enrollment Belgium | 0 participants | 8 participants | 8 participants |
| Region of Enrollment Canada | 13 participants | 13 participants | 0 participants |
| Region of Enrollment France | 5 participants | 16 participants | 11 participants |
| Region of Enrollment New Zealand | 3 participants | 4 participants | 1 participants |
| Region of Enrollment Singapore | 4 participants | 4 participants | 0 participants |
| Region of Enrollment South Africa | 1 participants | 4 participants | 3 participants |
| Region of Enrollment United States | 15 participants | 15 participants | 0 participants |
| Region of Enrollment Vietnam | 12 participants | 12 participants | 0 participants |
| Sex: Female, Male Female | 32 Participants | 45 Participants | 13 Participants |
| Sex: Female, Male Male | 29 Participants | 39 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 84 |
| other Total, other adverse events | 26 / 84 |
| serious Total, serious adverse events | 5 / 84 |
Outcome results
Primary
Percentage of Participants With Sustained Virologic Response 12 Weeks Post Treatment (SVR12)
SVR12 is defined as 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 actual dose of study drug.
Time frame: 12 weeks after last dose of study drug (week 20 or 24 depending on the treatment regimen)
Population: All enrolled participants who received at least one 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) |
|---|---|---|
| Genotype 5-infected | Percentage of Participants With Sustained Virologic Response 12 Weeks Post Treatment (SVR12) | 95.7 percentage of participants |
| Genotype 6-infected | Percentage of Participants With Sustained Virologic Response 12 Weeks Post Treatment (SVR12) | 98.4 percentage of participants |
Secondary
Percentage of Participants With On-treatment HCV Virologic Failure
HCV virologic failure was defined as one of the following conditions: * confirmed HCV RNA ≥ 100 IU/mL after HCV RNA \< 15 IU/mL during the Treatment Period; or 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 * HCV RNA ≥ 15 IU/mL at end of treatment with at least 6 weeks of treatment, where the HCV RNA value must be collected on or after Study Drug Day 36 and study drug duration ≥ 36 days.
Time frame: 8 or 12 weeks (depending on the treatment regimen)
Population: All enrolled participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Genotype 5-infected | Percentage of Participants With On-treatment HCV Virologic Failure | 0.0 percentage of participants |
| Genotype 6-infected | Percentage of Participants With On-treatment HCV Virologic Failure | 1.6 percentage of participants |
Secondary
Percentage of Participants With Relapse
Relapse was defined as confirmed HCV RNA ≥ 15 IU/mL between the end of treatment and 12 weeks after the last dose of study drug among participants who completed treatment as planned with HCV RNA \< 15 IU/mL at the end of treatment and had post-treatment HCV RNA data; participants who had been shown to be re-infected were not considered to have relapsed.
Time frame: End of treatment (week 8 or 12 depending on the treatment regimen) through 12 weeks after the end of treatment.
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) |
|---|---|---|
| Genotype 5-infected | Percentage of Participants With Relapse | 4.3 percentage of participants |
| Genotype 6-infected | Percentage of Participants With Relapse | 0.0 percentage of participants |