MK-5172/MK-3682 with MK-8742 or MK-8408 in HCV GT1 and GT2 Infected Subjects

Phase 1

Conditions: Chronic Hepatitis C infected patient
Therapeutic area: Diseases [C] - Virus Diseases [C02]

Registration Number: EUCTR2014-003304-73-DE

Lead Sponsor: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co.,Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 465

Inclusion Criteria

The following applies to Part A and Part B (unless otherwise specified):
1. be =18 years of age
2. HCV RNA (= 10,000 IU/mL in peripheral blood) at the time of screening
3. have documented chronic HCV GT1, GT2, or GT4 (NOTE: GT4 infected subjects are only eligible for enrollment in Part B) (with no evidence of non-typeable or mixed genotype) infection:
•Positive for anti-HCV antibody, HCV RNA, or any of the above HCV genotypes at least 6 months before screening, or
•Positive for anti-HCV antibody or HCV RNA at the time of screening with a liver biopsy consistent with chronic HCV infection (or a liver biopsy performed before enrollment with evidence of CHC disease, such as the presence of fibrosis)
4.Be otherwise healthy as determined by the medical history, physical examination, ECG, and clinical laboratory measurements performed at the time of screening
5.have liver disease staging assessment as follows:
Absence of cirrhosis is defined as any one of the following (both Part A and Part B):
•Liver biopsy performed within 24 months of Day 1 of this study showing absence of cirrhosis
•Fibroscan performed within 12 months of Day 1 of this study with a result of =12.5 kPa
•A Fibrosure® (Fibrotest®) score of =0.48 and Aspartate Aminotransferase to Platelet Ratio Index (APRI) of =1 during Screening
Compensated cirrhosis is defined as any one of the following (Part B only):
•A liver biopsy performed prior to Day 1 of this study showing cirrhosis (F4)
•Fibroscan performed within 12 calendar months of Day 1 of this study with a result >12.5 kPa
•A FibroSure® (Fibrotest®) performed during Screening with a score of >0.75 and an aspartate aminotransferase (AST): platelet ratio index (APRI) of >2. APRI formula: AST÷lab upper limit of normal (ULN) for AST x 100÷ {platelet count÷100} (APRI calculation to be provided by the central laboratory.)
6.be HCV treatment naïve
7.meet one of the following categories:

-not of reproductive potential
-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 and for 90 days after the last dose of study drug 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 barrier contraception during heterosexual activity. Acceptable methods of contraception are:
• intrauterine device (IUD) with or without local hormone release
• diaphragm with spermicide (cannot be used in conjunction with cervical cap/spermicide)
• cervical cap with spermicide (nulliparous women only)
• contraceptive sponge with spermicide (nulliparous women only)
• male condom with spermicide or female condom with spermicide (cannot be used together)
8. understand the study procedures, alternative treatments available, risks involved, and voluntarily agrees to participate .
9.provide written informed consent for the trial.
For Part B only:
For HIV co-infected subjects these additional criteria must also be met.
10. have HIV-1 infection documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry (Day 1) and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 p24 antigen, or plasma HIV-1 RNA viral load.
11. meet one of the following criteria:

Exclusion Criteria

1. 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 would interfere with the study procedures
2.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.
3.For cirrhotics (Parts B and C only):
a.subjects that are Child-Pugh Class B or C or who have a Pugh-Turcotte (CPT) score >5, must be excluded
4.coinfected with hepatitis B virus
5.coinfected with HIV (Part A only).
6.For subjects with HIV, has a history of opportunistic infection in the preceding 6 months prior to screening. A list of these events may be found in Appendix B of the following document: http://www.cdc.gov/mmwr/preview/mmwrhtml/00018871.htm
7.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.
8.has cirrhosis and liver imaging within 6 months of Day 1 showing evidence of hepatocellular carcinoma (HCC) or is under evaluation for HCC.
9.is taking or plans to take any of the prohibited medications listed in the protocol or is taking herbal supplements within 2 weeks of Day 1.
10.For Parts A and B only: 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.
11.has clinically-relevant drug or alcohol abuse within 12 months of screening. A positive drug screen will exclude subjects unless it can be explained by a prescribed medication; the diagnosis and prescription must be approved by the investigator.
12.is a female and is pregnant or breast-feeding, 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 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, or longer if dictated by local regulations.
13.has any of the following conditions:
a.Organ transplants (including hematopoietic stem cell transplants) other than cornea and hair.
b.Poor venous access that precludes routine peripheral blood sampling required for this trial.
c.subject with a history of gastric surgery or subject with a history of malabsorption disorders.
d.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 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.
e.Chronic pulmonary disease, including but not limited to: clinical chronic obstructive pulmonary disease, interstitial lung disease, pulmonary fib