Efficacy and Safety of MK-3682B (MK-5172 + MK-3682 + MK-8408) Fixed Dose Combination in Chronic HCV Participants Failing Prior Antiviral Treatment (MK-3682-021)



Status:Recruiting
Conditions:Infectious Disease, Infectious Disease, Gastrointestinal, Gastrointestinal, Hepatitis, Digestive Disease
Therapuetic Areas:Gastroenterology, Immunology / Infectious Diseases
Healthy:No
Age Range:18 - Any
Updated:4/14/2017
Start Date:December 10, 2015
End Date:September 5, 2018
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-3682B (MK-5172 + MK-3682 + MK-8408 Fixed Dose Combination (FDC)) in Subjects With Chronic HCV GT1 or GT3 Infection Who Have Failed a Direct Acting Antiviral Regimen

This is a randomized, multicenter, open-label trial of the combination regimen of MK-5172
(grazoprevir [GZR]) (100 mg), MK-3682 (450 mg) and MK-8408 (ruzasvir) (60 mg) for 16 weeks
with ribavirin (RBV) or 24 weeks without RBV in cirrhotic (C) or non-cirrhotic (NC)
hepatitis C virus (HCV) genotype (GT) 1 or GT3-infected participants who have previously
failed a direct-acting antiviral regimen (DAA). The combination regimen will be administered
as two fixed-dose combination (FDC) tablets, referred to as MK-3682B, given once-daily.

The study will evaluate the efficacy of the combination regimen of MK-5172 (GZR), MK-3682
and MK-8408 (ruzasvir) with or without ribavirin as assessed by the proportion of
participants achieving Sustained Virologic Response 12 weeks (SVR12) after the end of all
study therapy.

Prior to enrollment of GT3-infected subjects, the safety and efficacy data for GT3 subjects
being dosed in Part B of MK-3682-012 (NCT02332720) will be reviewed. Participants in
MK-5172-017 (NCT01667081) are eligible for enrollment in the study.

Inclusion Criteria:

- Has HCV RNA ≥ 10,000 IU/mL in peripheral blood at enrollment.

- Has documented chronic HCV GT1 or HCV GT3 infection (with no evidence of non-typeable
or mixed genotype)

- Has documented relapse, defined as having HCV RNA target not detected at
end-of-treatment, but HCV RNA quantifiable during follow-up, after treatment with one
of the following DAA regimens either by approved dosage and duration or by completion
of a clinical trial: GT1: SOF/LDV ± RBV; GT1: GZR/EBR ± RBV; GT3: SOF + RBV; GT3: SOF
+ PR; GT3: SOF + DCV ± RBV; GT3: SOF/LDV ± RBV. Participants who previously failed PR
treatment, with or without simepravir (SIM), boceprevir (BOC), or telaprevir (TPV),
prior to receiving DAA therapy, may also be enrolled.

- Is otherwise healthy.

- Has either absence of cirrhosis or presence of compensated cirrhosis.

- Is not of reproductive potential or is of reproductive potential and agrees to avoid
becoming pregnant or impregnating a partner beginning at least 2 weeks prior to
administration of the initial dose of study drug, through 6 months after taking the
last dose of study drug (or longer if dictated by local regulations), by complying
with one of the following: (1) practice abstinence from heterosexual activity OR (2)
use (or have their partner use) two forms of acceptable contraception during
heterosexual activity which may include oral contraceptives.

- For HIV co-infected participants additional criteria include: 1) documented HIV-1
infection 2) either not currently on antiretroviral therapy (ART) without plans to
initiate ART while participating in this study or has well controlled HIV on ART 3)
at least one 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:

- Is under the age of legal consent, is mentally or legally incapacitated, has
significant emotional problems at the time of pre-study screening visit or expected
during the conduct of the study or has a history of a clinically significant
psychiatric disorder which, in the opinion of the investigator, would interfere with
the study procedures.

- Has previously received a DAA containing regimen other than the permitted regimens
listed above.

- Did not complete their prior DAA therapy due to intolerance to the DAA regimen or who
failed the DAA regimen for reasons other than relapse (e.g., virologic breakthrough,
rebound or non-response, non-compliance, lost to follow-up, withdrew consent).

- 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.

- Has cirrhosis classified as Child-Pugh Class B or C or has a Pugh-Turcotte (CPT)
score >6

- Is coinfected with hepatitis B virus (HBV)

- For participants with HIV, has a history of opportunistic infection in the 6 months
prior to screening.

- Has a history of malignancy ≤5 years prior to enrollment 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.

- Is currently participating or has participated in a study with an investigational
compound within 30 days of signing informed consent and is not willing to refrain
from participating in another such study during the course of this study.
Participants participating in MK-5172-017 (NCT01667081) may be enrolled in this
study, MK- 3682-021.

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

- Is a female and is pregnant or breastfeeding or expecting to conceive or donate eggs
from at least 2 weeks prior to Day 1 through at least 6 months after last dose of
study drug, or longer if dictated by local regulations.

- Is a male whose female partner(s) is/are pregnant.

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

- Has history of gastric surgery or history of malabsorption disorders.

- Has current or history of any clinically significant cardiac
abnormalities/dysfunction or personal or family history of Torsade de pointes.

- Has chronic pulmonary disease.

- Has an hemoglobinopathy.

- Has 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).

- Has 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, and a
documented normal neurological examination at Day 1.

- Has history of stroke or transient ischemic attack.

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

- Has a medical condition requiring, or likely to require, chronic systemic
administration of corticosteroids, TNF antagonists, or other immunosuppressant drugs
during the course of the study

- Has evidence of history of chronic hepatitis not caused by HCV. Participants with
history of acute non-HCV-related hepatitis, which resolved >6 months before study
entry, may be enrolled.
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