A Phase III Randomized Clinical Trial to Study the Efficacy and Safety of the Combination Regimen of MK-5172/MK-8742 in Treatment-Naïve Subjects with Chronic HCV GT1, GT4, and GT6 Infection who are on Opiate Substitution Therapy.

Every year, 3*4 million people worldwide are newly infected with HCV, and
approximately 80% of these will progress to chronic infection . It is estimated
that 130*170 million people, or 2*3% of the world*s population, are chronically
infected with HCV. Long-term complications of chronic HCV infection develop in
chronically infected individuals over the course of several years to decade s,
including cirrhosis, end-stage liver disease and hepatocellular carcinoma
(HCC). More than 350 000 people die from HCV - related liver diseases every
year.

HCV has six major genotypes (GT), which can each be split into multiple
subtypes. The global distribution of HCV genotypes is diverse, which reflects
differences in epidemiology, modes of transmission and ethnic variability. HCV
GT 1, 2 and 3 have a fairly broad geographical distribution, whereas HCV GT 4,
5 and 6 are generally confined to spe cific geographical regions.

The goal of therapy for chronic HCV infection is eradication of the virus,
which is typically measured as a sustained virologic response (SVR). Until
recently, SVR at 24 weeks post treatment (SVR24) has been considered the gold
standard for treatment success; this end point is predictive of long term
eradication of the virus and correlates with a reduction in symptoms and in the
rate of negative clinical outcomes. However, there is evidence that most
patients who have an SVR at earlier time points (such as SVR12) maintain it
until week
24; therefore, the US FDA has concluded that SVR12 is suitable as a primary end
point for regulatory approval.

Until 2011, the standard of care (SOC) treatment for chronic HCV
infection with all genotypes was pegylated-interferon (peg-IFN) plus
ribavirin (RBV) (PR) administered for either 48 weeks (HCV GT 1, 4, 5, and 6)
or for 24 weeks (HCV GT 2 and 3). PR therapy led to SVR rates of 40%-50% in
those with GT1 and of 80% or more in those with GT 2 and 3 infections.

Subjects co-infected with HCV and HIV have SVR rates of 27 -44% when treated
with peginterferon plus ribavirin (PR) for 48 weeks. In HCV co-infected
patients, the addition of boceprevir and telaprevir to PR has been shown to
increase the efficacy of therapy substantially. Furthermore, the safety profile
in co-infected subjects was similar to that in monoinfected persons.

3.1 Primary Objective(s):
1) Objective:
To evaluate the efficacy of MK-5172 in combination with MK-8742 as assessed by
the proportion of subjects achieving SVR12 (Sustained Virologic Response 12
weeks after the end of all study therapy), defined as HCV RNA TD[u] or TND) 12 weeks after the end of all study therapy.

2) Objective:
To evaluate the safety and tolerability of MK -5172 in combination with MK-8742.


3.2 Secondary Objective(s):
Part A
1) Objective: To evaluate the efficacy of MK-5172 in combination with MK-8742
as assessed by the proportion of subjects achieving: SVR24 (Sustained Virologic
Response 24 weeks after the end of all study therapy), defined as HCV R NA

Part B
1) To evaluate the durability of SVR and the incidence of detectable HCV RNA,
classified as either relapse or reinfection, over a three year followup period
following the treatment/follow-up as defined in Part A .
2) To characterize the HCV virus detected during the Part A treatment and
follow-up periods and as well as in the Part B 3-year follow-up period
including:
a. To describe the presence of baseline viral resistance-associated variants
(RAVs)
b. To describe treatment emergent RAVs
c. To determine reinfection versus relapse

This is a randomized, parallel-group, placebo-controlled, multi-site, double
blind trial of 100 mg of MK-5172 in combination with 50 mg of MK-8742
(MK-5172A) in subjects with chronic Hepatitis C Virus (HCV), genotype (GT) 1,
4, or 6 infection who are on opiate
substitution therapy, to be conducted in conformance with Good Clinical
Practices. A total of 300, GT 1, 4, or 6 HCV subjects on opiate substitution
therapy will be enrolled. Approximately 20% of the enrolled subjects may have
evidence of cirrhosis at screening. Enrolled subjects may be co-infected with
HIV. All subjects must be treatment-naïve. Subjects in the immediate treatment
group will receive MK-5172A 100mg/50mg (100 mg MK-5172/50 mg MK-8742) for 12
weeks with 24 weeks of follow-up after dosing is completed. Subjects in the
deferred treatment group will receive Placebo for 12 weeks followed by 4 weeks
of follow-up and then 12 weeks of open-label treatment with MK-
5172A 100mg/50mg (100 mg MK-5172/50 mg MK-8742) with 24 weeks of follow-up
after dosing is completed.
All subjects who received at least one dose of MK-5172 in combination with
MK-8742 in Part A will be asked to participate in Part B (3-year followup).
Safety and tolerability will be carefully monitored throughout the study by the
SPONSOR (or designee) in accordance with standard procedures.

Part A:
Immediate Blinded Treatment:
Arm 1: MK-5172A 100mg/50mg (100 mg MK-5172/50mg MK- 8742) for 12 weeks

Deferred Treatment Blinded for first 12 weeks Followed by 12 Weeks of
Open-Label Therapy:

Arm 2: Placebo for 12 weeks followed by open-label treatment for 12 weeks

Part B: no intervention

Part A and B:
*Blood samples: drawing blood from your arm may cause pain, bruising,
lightheadedness, and rarely, infection.

Part A only:
* The electrocardiogram (ECG) procedure may cause minimal discomforts during
the attachment and removal of the ECG leads to and from the skin.

* Liver Biopsy: Pain at the biopsy site is the most frequent risk of
percutaneous liver biopsy, occurring in about 20 percent of patients. The risk
of excessive bleeding, called hemorrhage, is about 1 in 500 to 1 in 1,000. Risk
of death is about 1 in 10,000 to 1 in 12,000. If hemorrhage occurs, a
procedure called embolization, assisted by an x-ray procedure used to visualize
blood vessels called angiography, can be used to stop the bleeding. In some
cases, a blood transfusion is necessary. Surgery can also be used to stop a
hemorrhage. Other risks include puncture of other internal organs, infection,
and spread of cancer cells, called cancer seeding.

* FibroTest/FibroSure®: The main risks associated with blood tests are bruising
and some pain around the needle*s entry point.

* FibroScan: Generally there is no pain or discomfort associated with the
procedure.