Hepatitis C Virus (HCV)
Conditions
Keywords
Chronic Hepatitis C Virus, Chronic Kidney Disease, Glecaprevir, Pibrentasvir, Hepatitis C Virus Genotype, Compensated cirrhosis, Non-cirrhotic, Interferon (IFN), Treatment naïve, Sofosbuvir (SOF), Pegylated interferon (pegIFN), Ribavirin (RBV)
Brief summary
This was a Phase 3b, open-label, non-randomized, multicenter study to evaluate the efficacy and safety of glecaprevir/pibrentasvir (GLE/PIB) in participants with chronic hepatitis C virus (HCV) genotype (GT) 1 - 6 infection without liver cirrhosis or with compensated liver cirrhosis and with chronic renal impairment in participants who were either HCV treatment-naïve (TN) or prior treatment-experienced (TE) with interferon (IFN) or pegylated interferon (PegIFN) with or without ribavirin (RBV), or sofosbuvir (SOF) plus RBV with or without pegIFN.
Detailed description
The study included a 42-day screening period, a treatment period of either 8, 12, or 16 weeks, and a 24-week post-treatment period. The duration of treatment was determined by product labeling. Participants received glecaprevir/pibrentasvir (GLE/PIB) 300 mg/120 mg once daily. Participants who completed or prematurely discontinued the treatment period were followed for 24 weeks after their last dose of study drug to monitor safety, hepatitis C virus ribonucleic acid (HCV RNA), and the emergence and persistence of viral substitutions.
Interventions
Film-coated tablet
Sponsors
AbbVie
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female (of non-childbearing potential or using allowed contraceptive methods) at least 18 years of age time of Screening * Participant had a positive anti-hepatitis C virus (HCV) antibody (Ab) and plasma HCV ribonucleic acid (RNA) greater than or equal to 1000 IU/mL at the Screening Visit. * Participant had an estimated glomerular filtration rate (eGFR) less than 45 mL/min/1.73 m\^2 as estimated by the Modification of Diet in Renal Disease (MDRD) method at Screening according to the following formula: eGFR (mL/min/1.73 m\^2 ) = 175 × (Serum Creatinine) \^-1.154 × Age\^-0.203 × (0.742 if female) × (1.212 if black), or were dialysis dependent. Subjects requiring dialysis had to have been receiving dialysis for at least 1 month prior to enrollment, and may have been on hemodialysis or peritoneal dialysis. * Cirrhotic participants only: absence of hepatocellular carcinoma (HCC) 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. Participants who had an ultrasound with results suspicious of HCC followed by a subsequent negative CT or MRI of the liver were eligible for the study.
Exclusion criteria
* Female participants who were pregnant, breastfeeding, or were considering becoming pregnant during the study or for approximately 30 days after the last dose of study drug * Current hepatitis B virus (HBV) or human immunodeficiency virus (HIV) infection on screening tests, defined as: * Positive test result at Screening for hepatitis B surface antigen (HBsAg), or; * HBV deoxyribonucleic acid (DNA) greater than lower limit of quantification (LLOQ) in participants with isolated positive hepatitis B core antibody (HBcAb), (i.e., negative HBsAg and Anti-HBsAg), or; * Positive anti-HIV antibody (Ab). * Any current or historical clinical evidence of decompensated cirrhosis, including any current or past evidence of Child-Pugh B or C classification, hepatic encephalopathy or variceal bleeding; radiographic evidence of small ascites; or prior or current empiric use of lactulose/rifaximin for neurologic indications. Prophylactic use of beta blockers was not exclusionary. * Clinical history of acute renal failure in the 3 months prior to Screening * History of severe, life-threatening, or other significant sensitivity to any excipients of the study drugs * Clinically significant abnormalities or co-morbidities, or recent (within 6 months prior to study drug administration) alcohol or drug abuse that could preclude adherence to the protocol in the opinion of the investigator * Receipt of any investigational or commercially available direct acting anti-HCV agents other than sofosbuvir
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Sustained Virologic Response 12 Weeks Post Dosing (SVR12) | 12 weeks after the last actual dose of study drug | SVR12 was defined as hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification (LLOQ) 12 weeks after the last actual dose of study drug. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With On-treatment Virologic Failure | Up to 16 weeks | On-treatment virologic failure was defined as: * Confirmed increase from nadir in hepatitis C virus ribonucleic acid (HCV RNA) defined as confirmed increase of \> 1 log (subscript)10(subscript) IU/mL above nadir during treatment; or * Confirmed HCV RNA greater than or equal to 100 IU/mL after HCV RNA less than the lower limit of quantification (LLOQ) during study drug treatment; or * HCV RNA ≥ LLOQ at the 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 hepatitis C virus ribonucleic acid (HCV RNA) ≥ the lower limit of quantification (LLOQ) 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 \< LLOQ at the end of treatment and had post-treatment HCV RNA data; participants who had been shown to be reinfected were not considered to have relapsed. . |
Countries
Canada, Germany, Greece, Italy, Poland, Puerto Rico, South Korea, Spain, Sweden, United States
Participant flow
Pre-assignment details
Intent to treat population: all participants who received at least 1 dose of study drug
Participants by arm
| Arm | Count |
|---|---|
| GLE/PIB for 8, 12, or 16 Weeks Glecaprevir/pibrentasvir (GLE/PIB): three 100 mg/40 mg co-formulated tablets once daily with food | 101 |
| Total | 101 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
Baseline characteristics
| Characteristic | GLE/PIB for 8, 12, or 16 Weeks |
|---|---|
| Age, Continuous | 59.03 years STANDARD_DEVIATION 11 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 13 Participants |
| Race (NIH/OMB) Black or African American | 14 Participants |
| Race (NIH/OMB) More than one race | 0 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 | 74 Participants |
| Sex: Female, Male Female | 41 Participants |
| Sex: Female, Male Male | 60 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 101 |
| other Total, other adverse events | 27 / 101 |
| serious Total, serious adverse events | 12 / 101 |
Outcome results
Primary
Percentage of Participants Achieving Sustained Virologic Response 12 Weeks Post Dosing (SVR12)
SVR12 was defined as hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification (LLOQ) 12 weeks after the last actual dose of study drug.
Time frame: 12 weeks after the last actual dose of study drug
Population: Intent to treat population: all participants who received at least 1 dose of study drug; participants with missing data after backwards imputation were counted as non-responders
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GLE/PIB for 8, 12, or 16 Weeks | Percentage of Participants Achieving Sustained Virologic Response 12 Weeks Post Dosing (SVR12) | 97.0 percentage of participants |
Secondary
Percentage of Participants With On-treatment Virologic Failure
On-treatment virologic failure was defined as: * Confirmed increase from nadir in hepatitis C virus ribonucleic acid (HCV RNA) defined as confirmed increase of \> 1 log (subscript)10(subscript) IU/mL above nadir during treatment; or * Confirmed HCV RNA greater than or equal to 100 IU/mL after HCV RNA less than the lower limit of quantification (LLOQ) during study drug treatment; or * HCV RNA ≥ LLOQ at the end of treatment with at least 6 weeks of treatment
Time frame: Up to 16 weeks
Population: Intent to treat population: all participants who received at least 1 dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GLE/PIB for 8, 12, or 16 Weeks | Percentage of Participants With On-treatment Virologic Failure | 0 percentage of participants |
Secondary
Percentage of Participants With Post-treatment Relapse
Post-treatment relapse was defined as confirmed hepatitis C virus ribonucleic acid (HCV RNA) ≥ the lower limit of quantification (LLOQ) 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 \< LLOQ at the end of treatment and had post-treatment HCV RNA data; participants who had been shown to be reinfected were not considered to have relapsed. .
Time frame: Up to 12 weeks after the last dose of study drug
Population: Intent to treat population: all participants who received at least 1 dose of study drug and who completed treatment, had HCV RNA \< LLOQ at final treatment visit, and had at least one post-treatment HCV RNA value
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GLE/PIB for 8, 12, or 16 Weeks | Percentage of Participants With Post-treatment Relapse | 0 percentage of participants |