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
Condition: Hepatitis C Virus (HCV)
MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis; Hepatitis, Chronic
Intervention: Glecaprevir/pibrentasvir
Intervention description: Film-coated tablet
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 101.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
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)

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.
    

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