MK-5172/MK-3682 with MK-8742 or MK-8408 in HCV GT3, GT4, GT5 and GT6 Infected Subjects

Phase 1

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

Registration Number: EUCTR2014-003347-35-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: 500

Inclusion Criteria

The following applies to Part A and Part B (unless otherwise specified):
1.be =18 years of age on day of signing informed consent.
2.HCV RNA (= 10,000 IU/mL in peripheral blood) at the time of screening.
3.have documented chronic HCV GT3, GT4, GT5, GT6 (with no evidence of non-typeable or mixed genotype) infection.
•Positive for anti-HCV antibody, HCV RNA, or HCV genotype 3 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.Have a prior treatment history of:
a.HCV treatment-naïve (defined as no prior exposure to any interferon, ribavirin, or other approved or experimental HCV-specific direct-acting antiviral agent) (both Part A and Part B)
b.Prior virologic failure after treatment with a Peg-IFN/RBV regimen (the subject’s medical records must include sufficient detail of prior virologic failure to allow for categorization of prior response) (Part B only):
i.P/R Null Responder: <2 log10 IU/mL reduction in HCV RNA after at least 12 weeks of a Peg-IFN/RBV regimen.
ii.P/R Partial Responder: =2 log10 IU/mL reduction in HCV RNA after at least 12 weeks of treatment, but not achieving HCV RNA target not detected at end-of-treatment, with a Peg-IFN/RBV regimen.
iii.P/R Relapser: HCV RNA target not detected at end-of-treatment with a Peg-IFN/RBV regimen, but HCV RNA quantifiable (=LLOQ) during follow-up.
See protocol for exclusion criteria 7 to 9.
For Part B only:
For HIV coinfected 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:
a.not currently be on antiretroviral therapy (ART) and have no plans to initiate ART treatment while participating in this study.
i.subjects not on ART must have CD4+ T-cell count >500 cells/mm3 at screening
b.have well controlled HIV on AR

Exclusion Criteria

The following applies to Parts A, B and C (unless otherwise specified):
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, in the opinion of the investigator, 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 (Part B only):
a.subjects that are Child-Pugh Class B or C, or who have a Pugh-Turcotte (CPT) score >5, must be excluded.
4.is coinfected with hepatitis B virus (e.g. HBsAg positive).
5.is 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, including but not limited to St. John’s Wort (Hypericum perforatum) within 2 weeks of Day 1.
10.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 abuse within 12 months of screening.
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 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 or longer if dictated by local regulations.
13. Part C only: is a male whose female partner(s) is/are pregnant (this is a contraindication for ribavirin use).
see protocol for exclusion criterion 14.
15. has exclusionary laboratory values at the screening visit as listed in Table 6 of protocol.