There were no drug-related serious adverse events found in the study.
While glecaprevir/pibrentasvir (GLE/PIB) treatment is proven safe and effective in adults and adolescents with chronic hepatitis c virus (HCV) infections, the data is fairly limited in children.
A team, led by Maureen M. Jonas, Division of Gastroenterology, Hepatology, and Nutrition, Boston Children’s Hospital, Department of Pediatrics, Harvard Medical School, evaluated the pharmacokinetics, efficacy, and safety of a pediatric formulation of glecaprevir and pibrentasvir in children 3-12 years old.
In the DORA part 2 phase 2/3 nonrandomized, open-label study, the researchers examined children with chronic HCV infection, genotype (GT) 1‐6, with or without compensated cirrhosis. The patients were divided into 3 cohorts by age, cohort 2 (9–12 years), cohort 3 (6–9 years), and cohort 4 (3–6 years) and given weight-based doses of the treatment for 8,12, or 16 weeks.
The researchers sought primary endpoints of SVR12 and steady-state exposure and secondary endpoints of the rates of persistent viremia, relapse, and reinfection.
The team also assessed safety and laboratory abnormalities.
“Final pediatric dosages determined to be efficacious were 250 mg GLE + 100 mg PIB (in children weighing ≥ 30 kg to < 45 kg), 200 mg GLE + 80 mg PIB (≥ 20 kg to < 30 kg), and 150 mg GLE + 60 mg PIB (12 kg to < 20 kg),” the authors wrote.
A total of 80 patients participated in the trial and 96% (n = 77) achieved SVR12. However, 1 participant relapsed by post-treatment week 4 on the initial dose ratio.
In addition, no participants had virologic failures on the final dose ratio of GLE 50 mg/ PIB 20 mg and 2 non-responding participants prematurely discontinued the study.
The majority of adverse events were mild with treatment-related serious adverse events occurred. In addition, pharmacokinetic exposures were ultimately comparable to adults.
“A pediatric formulation of GLE/PIB was highly efficacious and well‐tolerated in chronic HCV‐infected children 3 ‐ < 12 years old,” the authors wrote.
Last year, researchers found glecaprevir/pibrentasvir after failure of sofosbuvir with an NS5A inhibitor for patients with HCV.
A team of investigators, led by Anna S. Lok, MD, Division of Gastroenterology and Hepatology, University of Michigan, performed a randomized, phase 3B, open-label, pragmatic trial of the safety and efficacy of 12 and 16 weeks of G/P, with or without ribavirin (RBV), in 177 patients with HCV genotype 1 (GT1) infection with treatment failure after sofosbuvir and an NS5A inhibitor.
The treatment failed in 13 (7.3%) patients with HCV genotype 1a infection, 6 (7.9%) in the first group, 3 (6.1%) in second group, 3 (6.1%) in the third group (6.1%), and 1 (3.4%) in the fourth group.
The majority of patients had baseline resistance-associated substitutions in NS5A.
Treatment-emergent resistance-associated substitutions in NS3 and NS5A were observed in 9 and 10 patients with treatment failure. While G/P was well-tolerated, ribavirin increased adverse events and did not increase efficacy.