The phase 2 C-WORTHY
trial evaluated Merck's investigational HCV protease inhibitor grazoprevir
plus NS5A inhibitor
elbasvir, taken with
or without ribavirin. After Part A saw good outcomes for previously untreated people
with genotype 1 hepatitis C and no liver cirrhosis, the study was expanded to
include more people with
traditional predictors of poor treatment response.
Overall, the trial included:
- 65
treatment-naive patients without cirrhosis in Part A, all treated for 12 weeks
- 94
treatment-naive patients without cirrhosis in Part B, treated for 8 or 12 weeks
- 59 patients
with HIV and HCV co-infection, without cirrhosis, all treated for 12 weeks
- 123
treatment-naive patients with cirrhosis, treated for 12 or 18 weeks
- 130 prior
null responders, with or without cirrhosis, treated for 12 or 18 weeks
Mark Sulkowski from
Johns Hopkins reported final combined results from the 218 patients with HCV
mono-infection and HIV/HCV co-infection without cirrhosis in both Part and A
and Part B.
Half of the participants
with HCV mono-infection and 80% of the participants with HIV/HCV co-infection
were men, most were white and the mean ages were 49 and 45 years, respectively.
Three-quarters had harder-to-treat HCV genotype 1a and most had unfavourable
IL28B gene variants. More than 90% had absent-to-mild liver fibrosis while 8%
had advanced fibrosis (stage F3).
The participants with
HIV and HCV co-infection were required to be on stable antiretroviral therapy
containing raltegravir (Isentress),
which was shown not to interact with the HCV drugs. They had CD4 cell counts
above 300 cells/mm3 (median 626 cells/mm3) and
undetectable HIV viral load for at least six months.
Among the participants
with HCV mono-infection, a group of 30 people with genotype 1a received
grazoprevir plus 50mg elbasvir for 8 weeks. Another 129 people
with genotype 1a or 1b were assigned to take grazoprevir plus either 20
or 50mg elbasvir plus ribavirin, or else 50mg elbasvir
without ribavirin, for 12 weeks. The 59 people with co-infection were
assigned
to take grazoprevir plus 50mg elbasvir either with or without
ribavirin for 12 weeks.
The primary intent-to-treat
analysis showed that 98% of people with HCV mono-infection treated with grazoprevir plus elbasvir alone for 12 weeks, and 93% of
those whose treatment included ribavirin, achieved SVR12, or continued
undetectable HCV RNA at 12 weeks after finishing treatment. Among patients with
genotype 1a treated with the triple combination for just 8 weeks, however,
SVR12 fell to 80%. The takeaway message, Sulkowski said, is that the 8-week
regimen was too short for this group.
Turning to the participants
with HIV and HCV co-infection, 87% of people treated with grazoprevir plus elbasvir alone for 12 weeks, and 97% of
those who included ribavirin, achieved SVR12.
Combining all participants
treated for 12 weeks, 92% of patients with genotype 1a taking grazoprevir plus elbasvir alone and 95% who added
ribavirin achieved SVR12. For patients with genotype 1b, the SVR12 rates were
reversed: 95% with grazoprevir plus elbasvir alone and 92% with ribavirin
added.
Across all groups,
three people experienced viral breakthrough during therapy (one taking
ribavirin and two not on ribavirin). Nine people experienced post-treatment
relapse, five of whom were in the 8-week treatment arm.
The grazoprevir/elbasvir regimens used in C-WORTHY were
generally safe and well-tolerated. A total of three participants experienced
serious adverse events, but no one stopped treatment early for this reason. Nine
per cent of people with HCV mono-infection taking ribavirin – but interestingly,
just 3% of people with HIV co-infection – developed anaemia. The most common
side-effects were fatigue, headache, nausea and diarrhoea, with patients who
had HIV co-infection reporting fewer symptoms. None of the HIV-positive
participants experienced HIV viral breakthrough and CD4 cell counts remained
stable.
In response to a
question about patients with HIV co-infection using other antiretrovirals
besides raltegravir, Sulkowski said that studies were underway testing the
Merck HCV drugs with dolutegravir (Tivicay,
also in the Triumeq co-formulation) and
rilpivirine (Edurant, also in Eviplera or Complera).