A Study to Evaluate the Pharmacokinetics, Safety, and Efficacy of Glecaprevir/Pibrentasvir in Pediatric Subjects With Genotypes 1-6 Chronic Hepatitis C Virus (HCV) Infection
Condition: Hepatitis C Virus (HCV)
MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis; Hepatitis, Chronic
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      The objectives of this study are to assess the pharmacokinetics, safety, and efficacy of
      glecaprevir/pibrentasvir adult formulation in adolescents ages 12 to 17 years and a pediatric
      formulation of glecaprevir and pibrentasvir in children ages 3 to < 12 years.
    

Detailed description: 
      This was a multicenter study to evaluate the pharmacokinetics (PK), efficacy, and safety of
      glecaprevir (GLE) and pibrentasvir (PIB) treatment for 8, 12, or 16 weeks in hepatitis C
      virus (HCV) genotype 1 - 6 (GT1 - GT6)-infected pediatric participants 3 to < 18 years of
      age, with or without compensated cirrhosis, with or without human immunodeficiency virus
      (HIV) coinfection, who are either treatment-naïve (TN), treatment-experienced (TE) with
      pegylated interferon (pegIFN) with or without ribavirin (RBV), or TE with sofosbuvir (SOF) +
      RBV with or without pegIFN.

      The study was divided into 2 parts, according to the formulation of GLE/PIB administered.
      Part 1 of the study enrolled HCV GT1 - GT6 infected adolescent participants into the 12 to <
      18 years old age group who were willing to swallow the adult formulation of GLE/PIB (Cohort
      1). Part 2 of the study enrolled HCV GT1 - GT6 infected pediatric participants divided into
      the 9 to < 12 (Cohort 2), 6 to < 9 (Cohort 3), and 3 to < 6 (Cohort 4) years old age groups,
      to receive the pediatric formulation of GLE + PIB. Part 1 enrolled first and once the
      pediatric formulation was available enrollment into Part 2 commenced, with each cohort
      enrolled in parallel.

      In each cohort, the first group of participants were enrolled into an intense
      pharmacokinetics (IPK) portion to characterize the PK and safety in each age group, followed
      by enrollment into a non-IPK safety/efficacy portion. Study participants enrolled in the IPK
      portion must have been HIV-negative, treatment-naive, and have an identified HCV genotype. In
      the IPK portion the first approximately six participants received an initial proposed dose of
      GLE and PIB based on the child's weight and age at screening. PK samples from these
      participants were evaluated to determine if therapeutic efficacious exposures were attained,
      comparable to those of adults, and if any dose adjustments were needed. After the intensive
      PK analysis results for the first six participants were available, enrollment of the
      remaining IPK portion resumed with subsequent participants receiving an adjusted final dose
      as applicable. Additional participants may have been required for further intensive PK
      analysis per age cohort if therapeutic exposure targets were not achieved.

      Enrollment into the non-IPK safety and efficacy portions began when the dosing
      recommendations per age group based on the PK and clinical data from the IPK analysis were
      ascertained.
    

Intervention name(s): Glecaprevir/Pibrentasvir Adult Formulation; Glecaprevir + Pibrentasvir Pediatric Formulation
Intervention type(s): Drug; Drug
Intervention description(s): Co-formulated film-coated tablet (100 mg/40 mg); Film-coated pellets/granules (15.67%/8.25%) administered by mixing with a small amount (1-2 teaspoons) of a soft food vehicle, such as hazelnut spread, Greek yogurt, or peanut butter.
Other intervention name(s): ABT-493/ABT-530; MAVYRET®; ABT-493/ABT-530
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Chronic Hepatitis C Virus; Glecaprevir; Pibrentasvir; Pharmacokinetic; Treatment naïve; Treatment experienced; Interferon (IFN); Pegylated interferon (pegIFN); Ribavirin (RBV); Sofosbuvir; Non-cirrhotic cirrhosis; Compensated (Child-Pugh A) cirrhosis