Efficacy and Safety of Grazoprevir (MK-5172) and MK-3682 With Elbasvir (MK-8742) or MK-8408 for Chronic Hepatitis C Virus (HCV) Genotype (GT) 3, GT4, GT5, and GT6 Infection (MK-3682-012)



Status:Recruiting
Conditions:Hepatitis, Hepatitis
Therapuetic Areas:Immunology / Infectious Diseases
Healthy:No
Age Range:18 - Any
Updated:6/30/2016
Start Date:January 2015
End Date:April 2017
Contact:Toll Free Number
Phone:1-888-577-8839

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A Phase II, Randomized, Open-Label Clinical Trial to Study the Efficacy and Safety of the Combination Regimen of MK-5172 and MK-3682 With Either MK-8742 or MK-8408 in Subjects With Chronic HCV GT3, GT4, GT5, and GT6 Infection

This is a randomized, three-part, parallel-group, open-label trial of grazoprevir (MK-5172)
(100 mg) and MK-3682 (300 mg or 450 mg) with either elbasvir (MK-8742) (50 mg) or MK-8408
(60 mg), and with and without ribavirin (RBV), in treatment-naive (TN) or
treatment-experienced (TE) cirrhotic (C) or non-cirrhotic (NC) participants infected with
hepatitis C virus (HCV) genotype (GT) 3, GT4, GT5, or GT6. Part A will consist of 4 arms to
evaluate the safety of dose combinations. In Part B, participants will take 2 MK-3682B fixed
dose combination (FDC) tablets once daily (q.d.) by mouth, with or without twice-daily
(b.i.d.) RBV (200 mg capsules; weight-based dosing). Participants who relapse following
completion of therapy in Part A will be offered the option of retreatment with 16 weeks of
MK-3682B with RBV in Part C (data obtained from Part C will not be used in the analysis of
outcome measures).

In Part A, study therapy will be administered as separate products, each taken q.d. by
mouth. In Part B and Part C, participants will take 2 MK-3682B FDC tablets q.d. by mouth;
each MK-3682B FDC tablet contains grazoprevir 50 mg + MK-3682 225 mg + MK-8408 30 mg.

Inclusion Criteria:

- Has documented chronic HCV GT3, GT4, GT5, or GT6 with no evidence of non-typeable or
mixed GT infection

- Is otherwise healthy as determined by the medical history, physical examination,
electrocardiogram (ECG), and clinical laboratory measurements performed at the time
of screening

- Has cirrhosis of the liver (Part B only) or is non-cirrhotic (Part A and B)

- Is HCV treatment-naïve or has experienced virologic failure after completing a prior
Pegylated Interferon/Ribavirin (Peg-IFN/RBV) regimen

- Is of non childbearing potential or agrees to avoid becoming pregnant or impregnating
a partner beginning at least 2 weeks prior to administration of the initial dose of
study drug and for 14 days after the last dose of study drug if not taking RBV, or
for 6 months after the last dose of study drug if taking RBV (or longer if dictated
by local regulations). If not abstinent from heterosexual activity, participants in
Part A must use 2 acceptable forms of barrier contraception whereas participants in
Parts B and C must use 2 acceptable forms of contraception which may include oral
contraceptives

Part B only:

- If coinfected with human immunodeficiency virus (HIV) is not currently on
antiretroviral therapy (ART) and has no plans to initiate ART treatment while
participating in this study OR has well-controlled HIV on ART.

- Has at least 1 viable antiretroviral regimen alternative beyond their current regimen
in the event of HIV virologic failure and the development of anti-retroviral drug
resistance.

Exclusion Criteria:

Parts A, B, and C (unless otherwise specified):

- Has evidence of decompensated liver disease manifested by the presence of or history
of ascites, esophageal or gastric variceal bleeding, hepatic encephalopathy or other
signs or symptoms of advanced liver disease.

- If cirrhotic (Part B only), is Child-Pugh Class B or C or has a Pugh-Turcotte (CPT)
score >5.

- Is coinfected with hepatitis B virus (Parts A, B, and C) or is coinfected with HIV
(Part A only; HIV coinfected participants are eligible for Parts B and C).

- If coinfected with HIV, has a history of opportunistic infection in the preceding 6
months prior to screening.

- Has a history of malignancy ≤5 years prior to signing informed consent except for
adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer
or carcinoma in situ; or is under evaluation for other active or suspected
malignancy.

- Has cirrhosis and liver imaging within 6 months of Day 1 showing evidence of
hepatocellular carcinoma (HCC) or is under evaluation for HCC.

- Has clinically-relevant drug or alcohol abuse within 12 months of screening.

- Is female and is pregnant or breastfeeding, or expecting to conceive or donate eggs
from at least 2 weeks prior to Day 1 and 90 days after the last dose of study
medication, or longer if dictated by local regulations OR a male subject who is
expecting to donate sperm from at least 2 weeks prior to day 1 until 90 days after
the last dose of study medication.

- Has any of the following conditions:

- Organ transplants (including hematopoietic stem cell transplants) other than cornea
and hair.

- Poor venous access that precludes routine peripheral blood sampling required for this
trial.

- History of gastric surgery (e.g., stapling, bypass) or a history of malabsorption
disorders (e.g., celiac sprue disease).

- Current or history of any clinically significant cardiac abnormalities/dysfunction,
including but not limited to: angina, congestive heart failure, myocardial
infarction, pulmonary hypertension, complex congenital heart disease, cardiomyopathy,
significant arrhythmia, uncontrolled hypertension, a history of use of antianginal or
anti-arrythmic agents for cardiac conditions, prolonged ECG QTc interval (>470 ms for
males or >480 ms for females by either the Bazett or Fridericia formula) at the
screening visit, personal or family history of Torsade de pointes.

- Chronic pulmonary disease, including but not limited to: clinically significant
chronic obstructive pulmonary disease, interstitial lung disease, pulmonary fibrosis,
sarcoidosis.

- Central nervous system (CNS) trauma requiring intubation, intracranial pressure
monitoring, brain meningeal or skull surgery, or resulting in seizure, coma,
permanent neurologic deficits, abnormal brain imaging, or cerebral spinal fluid (CSF)
leak. Prior brain hemorrhage and/or intracranial aneurysms (whether adequately
repaired or not).

- Current or history of seizure disorder unless seizure was >10 years ago, a single
isolated event, no history of or current use of anti-seizure medications prescribed,
and a normal neurological examination is documented in trial files within 6 months of
Day 1.

- Has a history of stroke or transient ischemic attack.

- Has a history of a medical/surgical condition that resulted in hospitalization within
the 3 months prior to enrollment, other than for minor elective procedures.

- Has medical/surgical conditions that may result in a need for hospitalization during
the period of the study.

- Has any medical condition requiring, or likely to require, chronic systemic
administration of corticosteroids, tumor necrosis factor (TNF) antagonists, or other
immunosuppressant drugs during the course of the trial.

- Has any condition, prestudy laboratory or ECG abnormality or history of any illness,
which, in the opinion of the investigator, might confound the results of the study or
pose additional risk in administering the study drugs to the subject.

- Has had a life-threatening serious adverse event (SAE) during the screening period.

- Has evidence of history of chronic hepatitis not caused by HCV, including but not
limited to nonalcoholic steatohepatitis (NASH), drug-induced hepatitis,
hemochromatosis, Wilson's disease, α1-antitrypsin deficiency, alcoholic liver disease
and autoimmune hepatitis Parts B and C only: is a male whose female partner(s) is/are
pregnant
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