Douglas Dieterich from Mount Sinai
School of Medicine presented the latest findings from Study 110, a Phase 2
trial testing telaprevir in combination with pegylated interferon/ribavirin in
previously untreated coinfected patients with difficult-to-treat HCV genotype
1. Initial data were presented at last year's conference, with
further follow-up at the Liver Meeting last November.
The study consisted of two parts. Part A included
13 coinfected participants who had CD4 T-cell counts of at least 500 cells/mm3
and were not yet taking antiretroviral therapy (ART). Part B included 47 people
on ART; 24 took efavirenz (Sustiva or Stocrin) plus tenofovir (Viread)
and emtricitabine (Emtriva), while 23 took ritonavir-boosted atazanavir
(Reyataz) with either lamivudine (Epivir) or emtricitabine.
Most participants were men, with an average age of
about 45 years. Part A included a higher proportion of people of African
descent (a group that does not respond as well to interferon-based therapy).
About half in Part A and 75% in Part B had HCV genotype 1a, the rest 1b. Most
had high baseline HCV viral load about 10% had advanced liver fibrosis or
cirrhosis. Median CD4 counts in Part A and B were approximately 600 and 500
cells/mm3, respectively; patients on ART had suppressed HIV RNA
below 50 copies/ml.
In both parts of the study, participants were
randomly assigned to receive either telaprevir or placebo in combination with
180 mcg/week pegylated interferon alfa-2a (Pegasys) plus ribavirin.
Triple therapy continued for 12 weeks, followed by pegylated
interferon/ribavirin alone through week 48.
Patients taking atazanavir received the usual
telaprevir dose of 750mg three times daily; to compensate for a known
drug-drug interaction that lowers telaprevir levels, those taking efavirenz
increased their dose to 1125mg three times daily.
Two patients (5%) in the triple therapy arm and seven
(32%) taking pegylated interferon/ribavirin alone stopped treatment prematurely due to poor early response according to
predefined "futility" rules.
Dieterich
reported rates of sustained virological response, or continued undetectable
viral load, at 12 weeks after completion of treatment, known as SVR12. This has
been shown to be a good predictor of 24-week SVR, generally considered a cure.
Overall, 74% of
patients taking telaprevir achieved SVR12, compared with just 45% of those
taking pegylated interferon/ribavirin alone. Among participants off ART in Part
A, SVR12 rates were 71% and 33%, respectively. By ART regimen, 69% using the
efavirenz combination and 80% using boosted atazanavir achieved SVR12 with
telaprevir, compared with 50% for both regimens with pegylated
interferon/ribavirin alone.
One telaprevir
recipient (3%) and two placebo recipients (15%) experienced HCV relapse after
completing therapy. Three people on the telaprevir combination experienced HCV
RNA breakthrough while on treatment. No participants showed evidence of HIV
viral load rebound. Absolute CD4 cell counts fell in both arms
– a known effect of
interferon
– but CD4 cell percentages did not
change.
People taking telaprevir experienced
more side-effects overall than those on pegylated interferon/ribavirin alone.
Three people on telaprevir, but none in the control group, discontinued
treatment early due to adverse events. Adverse events that occurred at least
10% more often among telaprevir recipients compared with placebo recipients
included pruritis or itching (39% vs 9%), headache (37% vs 27%), nausea (34% vs
23%), skin rash (34% vs 23%), fever (21% vs 9%) and depression (21% vs 9%);
insomnia and weight loss were more common in the control group. No patients in
either arm experienced severe rash and anaemia was equally common in both
groups (18%).
"Higher SVR12 rates were
observed in chronic genotype 1 patients treated with telaprevir combination
treatment," the researchers concluded. "Overall safety and
tolerability profile was comparable to that previously observed in chronic
genotype 1 HCV monoinfected patients."