As part of its phase three development programme, the multinational UNITY-2 trial tested the TRIO regimen
in more than 200 people with chronic hepatitis C who have liver cirrhosis – a
group with hepatitis that is more difficult to treat and often requires longer or more
intensive therapy. Andrew Muir from Duke University School of Medicine
presented late-breaking results on Monday.
A total of 112 previously untreated
participants (treatment-naive) and 90 treatment-experienced participants were randomly assigned to
take the TRIO regimen twice daily either with placebo or with weight-based
ribavirin for 12 weeks. Participants were followed through week 24 to determine
sustained virological response, or continued undetectable HCV viral load, at 12
weeks after completing treatment (SVR12), which is considered a cure.
About two-thirds of study participants
were men, most were white and the median age was 59 years. About 70% of
treatment-naive and 78% of treatment-experienced participants had genotype 1a and most
had high baseline viral load. Three-quarters had unfavourable IL28B gene variants
associated with poor response to interferon. All had cirrhosis confirmed by
liver biopsies or non-invasive methods, and one-quarter had a platelet count
<100,000/mm3, indicating advanced disease. In the
treatment-experienced cohort more than one-third were prior null responders –
the hardest group to treat.
Looking first at the previously untreated cohort, 93% of participants
treated with the TRIO regimen alone and 98% who received TRIO plus ribavirin
achieved SVR12. In the treatment-experienced cohort, SVR12 rates were 87% and
93%, respectively. Collapsing these groups, 90% of all
patients who received TRIO alone and 96% who used TRIO plus ribavirin were
cured.
Breaking this down by HCV subtype, all but
one person with genotype 1b achieved SVR12; the individual who was not cured
was treatment-experienced and used TRIO alone. Among treatment-naive people
with genotype 1a, 90% taking TRIO alone and 97% taking TRIO plus ribavirin
achieved SVR12; among treatment-experienced patients with genotype 1a, the corresponding
rates were 86% and 91%.
Other factors including sex, age, baseline
viral load, IL28B gene pattern and platelet count did not noticeably affect
treatment response to either TRIO alone or TRIO plus ribavirin.
Among people who did not achieve SVR12,
three had detectable HCV RNA while still on treatment, all of whom were
treatment-experienced. Ten people experienced viral relapse after finishing
treatment, nine of whom were treated with TRIO without ribavirin.
Looking at resistance, the presence of
resistance-associated viral variants at baseline did not appear to affect
sustained response rates, as 28 of the 30 people with NS5A or NS3 variants
still achieved SVR12. Several patients without SVR – all but one with genotype
1a – developed various emergent resistance-associated variants.
The TRIO regimen was generally safe and
well-tolerated. There were two serious adverse events in the TRIO-only arm and seven
in the TRIO plus ribavirin arm. Two ribavirin recipients discontinued therapy early
due to adverse events, but both went on to achieve SVR12.
The
most common side-effects reported by
at least 10% of participants were fatigue, headache, nausea, diarrhoea,
insomnia and itching. Most side-effects were more common in the
ribavirin arms. Five per cent of ribavirin recipients, but no one taking
TRIO alone, developed anaemia.