A Study to Evaluate the Efficacy and Safety of Glecaprevir/Pibrentasvir in Adults With Chronic Hepatitis C Virus Genotype 1 - 6 Infection and Renal Impairment
A Study to Evaluate the Efficacy and Safety of Glecaprevir/Pibrentasvir in Adults With Chronic Hepatitis C Virus Genotype 1 - 6 Infection and Renal Impairment
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.
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.
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