C-SURFER Trial is First to Investigate an All-Oral Ribavirin-Free
Hepatitis C Treatment Regimen in Treatment-Naïve and
Treatment-Experienced Patients with Advanced Chronic Kidney Disease
Infected with Hepatitis C Virus Genotype 1
VIENNA--(BUSINESS WIRE)--Merck (NYSE:MRK), known as MSD outside the United States and Canada,
today announced the first presentation of data from C-SURFER, the
company’s Phase 2/3 clinical trial evaluating the investigational
once-daily treatment regimen of grazoprevir (100mg) and elbasvir (50mg)
in patients with advanced chronic kidney disease (CKD) infected with
chronic hepatitis C virus (HCV) genotype 1 (GT1).1
Treatment-naïve patients and patients who failed prior pegylated
interferon HCV therapy, with or without cirrhosis, all of whom had CKD
stages 4 or 5, were enrolled.2 Following 12 weeks of
treatment with grazoprevir and elbasvir, 99 percent (115/116) of
patients in the pre-specified primary population for analysis of
efficacy data achieved a sustained virologic response 12 weeks after the
completion of treatment (SVR12).3 These data will be
presented today at The
International Liver CongressTM 2015 – the 50th
annual congress of the European Association for the Study of the Liver
(late breaking E-Poster #LP02).
“There is an unmet medical need to treat chronic hepatitis C virus
infection in patients with advanced chronic kidney disease,” said Dr.
Howard Monsour, Jr., chief of hepatology, Houston Methodist Hospital,
Houston, Texas. “In this trial, the first to investigate an all-oral
ribavirin-free treatment regimen in treatment-naïve and
treatment-experienced CKD patients, treatment with grazoprevir and
elbasvir for 12 weeks was effective in this study population with HCV
genotype 1 infection.”
The ongoing C-SURFER Phase 2/3 clinical trial is a randomized,
parallel-group, placebo-controlled study evaluating patients infected
with chronic HCV GT1 with advanced CKD with or without liver cirrhosis.
Patients were randomized to one of two study arms:
-
Immediate treatment group (ITG), grazoprevir plus elbasvir (blinded)
once-daily for 12 weeks (n=111);
-
Deferred treatment group (DTG), initially placebo (control arm) for 12
weeks followed by a four week follow-up period and then treatment with
grazoprevir plus elbasvir (open label) once-daily for 12 weeks (n=113).
In addition, 11 patients received grazoprevir plus elbasvir (open label)
once-daily for 12 weeks with intensive pharmacokinetic sampling.
Of the 122 patients who received grazoprevir plus elbasvir, 83 percent
were treatment-naïve, 36 percent had diabetes, 18 percent had stage 4
CKD, 82 percent had stage 5 CKD, 75 percent were receiving hemodialysis
and 45 percent were African-American. Among those patients who received
at least one dose of grazoprevir plus elbasvir, five percent (6/122)
were excluded from the pre-specified primary efficacy analysis
population, or modified full analysis set, due to missing data caused by
death or early discontinuation for reasons unrelated to study drug. In
the modified full analysis set, 99 percent (115/116) of patients
receiving grazoprevir plus elbasvir achieved SVR12. One GT1b infected,
non-cirrhotic, interferon-intolerant patient showed a viral relapse at
follow-up week 12. Within the modified full analysis set, efficacy was
consistent across the patient sub-populations assessed. In a supportive
analysis of all 122 patients who received at least one dose of
grazoprevir plus elbasvir in the ITG arms, including patients who did
not complete the study for reasons not related to study drug, 94 percent
(115/122) of patients achieved SVR12.
“Merck’s broad clinical development program includes studies dedicated
to bringing a once-daily regimen to diverse populations of patients
infected with chronic HCV, including certain types of patients with
co-morbidities, such as advanced chronic kidney disease,” said Dr. Eliav
Barr, vice president, infectious diseases, Merck Research Laboratories.
“These data highlight how emerging innovations in chronic hepatitis C
treatment may lead to new options for patient populations in which it
historically has been difficult to achieve high rates of sustained viral
clearance.”
No patients in the ITG arms discontinued treatment due to adverse events
(AEs), while four percent (5/113) of patients in the comparator placebo
phase of the DTG arm discontinued treatment due to AEs. The rates of
serious AEs reported were 14 percent (16/111) in the ITG arms and 17
percent (19/113) in the placebo control DTG arm. The most common
treatment-related AEs in the ITG arms and DTG arm (placebo) were
headache (17%, 17%), nausea (15%, 16%) and fatigue (10%, 15%),
respectively. There were four deaths reported during the initial
treatment phase and the first 14 days of study follow-up. One patient
(1%) in the open label arm died from cardiac arrest (not considered
related to study medicine) and three patients (2%) in the placebo group
died from aortic aneurysm, pneumonia and an unknown cause.
On April 8, 2015, the company announced that the U.S. Food and Drug
Administration (FDA) had granted Breakthrough Therapy designation to
grazoprevir/elbasvir for the treatment of patients infected with chronic
HCV GT1 with end-stage renal disease on hemodialysis and patients
infected with chronic HCV GT4. Breakthrough Therapy designation is
intended to expedite the development and review of a candidate that is
planned for use, alone or in combination, to treat a serious or
life-threatening disease or condition when preliminary clinical evidence
indicates that the drug may demonstrate substantial improvement over
existing therapies on one or more clinically significant endpoints.
About C-SURFER
C-SURFER
is a Phase 2/3 clinical trial evaluating Merck’s investigational
grazoprevir plus elbasvir in patients infected with chronic HCV GT1 and
with advanced chronic kidney disease (stages 4 and 5, including patients
on hemodialysis) with or without liver cirrhosis, which are among those
with HCV infection who are most difficult to treat, over 12 weeks.
About Chronic HCV Infection and Chronic Kidney Disease
Chronic HCV infection is both a cause and complication of the treatment
of CKD. In patients with CKD, chronic HCV infection is associated with
an increased risk of accelerated loss of remaining kidney function,
kidney transplant failure and death. Furthermore, patients with chronic
HCV infection and advanced CKD represent an unmet need due to a lack of
demonstrated HCV treatment options for this group.
About Grazoprevir/Elbasvir
Grazoprevir/elbasvir is an investigational, once-daily single tablet
regimen consisting of grazoprevir (NS3/4A protease inhibitor) and
elbasvir (NS5A replication complex inhibitor). As part of Merck’s broad
clinical trials program, grazoprevir/elbasvir is being studied in
multiple HCV genotypes and in patients with difficult-to-treat
conditions such as HIV/HCV co-infection, advanced chronic kidney
disease, inherited blood disorders, liver cirrhosis and those on opiate
substitution therapy.
Read complete press release here... Labels: C-SURFER, chronic kidney disease (CKD), EASL 2015, grazoprevir/elbasvir, Merck