ENDURANCE-4 tested the combination in previously untreated
or treatment-experienced people with genotypes 4, 5 or 6, without cirrhosis.
The study recruited treatment-experienced people previously exposed to either
pegylated interferon plus ribavirin or to sofosbuvir with or without ribavirin.
The study excluded people with hepatitis B or HIV co-infection.
All participants received glecaprevir and pibrentasvir
(300mg/120mg) once daily for 12 weeks.
The study recruited 121 people, 76 with genotype 4, 26 with
genotype 5 and 19 with genotype 6. The overall study population was 64% male,
71% white, 8% black, with an average age of 54 years. The median body mass
index was 24.8.
As in other ENDURANCE studies the vast majority of
participants had less advanced liver disease (86% F0/F1), with 7% having F2 and
7% having F3 fibrosis. Approximately two-thirds (68%) were previously untreated
and all treatment-experienced participants had previous exposure only to
In the overall study population intent-to-treat analysis
showed that 99% achieved SVR12. One person in the genotype 4 arm discontinued
treatment on day 12 due to a transient ischaemic attack. Two other participants
discontinued treatment before the end of the treatment period due to anxiety
and to heartburn respectively. Both achieved SVR12. No cases of virologic
breakthrough or rebound occurred in the study population.
The most common adverse events were headache (21%) and
fatigue (17%). No grade 3 laboratory adverse events were observed.