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

Conditions: Hepatitis C Virus (HCV)

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.

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.

Eligibility criteria:
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

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)