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-PL

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 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 GT1a, GT1b, or GT2
4. Be otherwise healthy 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
• Fibroscan performed within 12 months of Day 1 a result of =12.5 kPa
• A Fibrosure® (Fibrotest®) score of =0.48 and APRI Index 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 showing cirrhosis (F4)
• Fibroscan performed within 12 calendar months of Day 1 with a result >12.5 kPa
• A FibroSure® (Fibrotest®) performed during Screening with a score of >0.75 and an (APRI) of >2.
6. be HCV treatment naïve (both Part A and Part B)
7. meet one of the following categories:
a. The subject is a male who is not of reproductive potential, defined as a male who has azoospermia
b. The subject is a female who is not of reproductive potential, defined as a female who either: (1) is postmenopausal and have a documented follicle stimulating hormone (FSH) level in the postmenopausal range at pretrial (screening); (2) has had a hysterectomy and/or bilateral oophorectomy, bilateral salpingectomy, or bilateral tubal ligation/occlusion at least 6 weeks prior to screening; OR (3) has a congenital or acquired condition that prevents childbearing.
c. The subject is a female or a male who 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, for 6 months after taking 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 contraception during heterosexual activity. Acceptable methods of contraception are‡:
• oral contraceptives (Part B and C only)
• Intrauterine device (IUD) with or without local hormone release
• diaphragm with spermicide
• cervical cap with spermicide
• contraceptive sponge with spermicide
• male condom with spermicide or female condom with spermicide
If male, subjects must agree to use a condom with spermicide or abstain from sexual intercourse during the trial until 6 months after the last dose of trial drug

Spermicides alone are not an acceptable method of contraception.
Note: In Part A, Oral contraceptives are not allowed as a method of birth control.

8. understand the study procedures, alternative treatments available, risks involved with the study, and voluntarily agrees to participate by giving written informed consent.
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 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:
1. not currently be on antiretroviral therapy (ART) and

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
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
4. Co-infected with hepatitis B virus
5. Co-infected with HIV (Part A only)
6. For subjects with HIV, has a history of opportunistic infection in the preceding 6 months prior to screening.
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;
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)

12. a female and is pregnant or breastfeeding or expecting to conceive or donate eggs OR is a male subject who is expecting to donate sperm or planning to impregnate female partner(s) from at least two weeks prior to Day 1 through at least 6 months after last dose of study drug,
13. Parts B and C only: is a male whose female partner(s) is/are pregnant
14. has any of the following conditions:
a. Organ transplants other than cornea and hair.
b. Poor venous access that precludes routine peripheral blood sampling.
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 or anti-arrhythmic agents for cardiac conditions, prolonged ECG QTc interval (>470 ms for males or >480 ms for females), personal or family history of Torsade de pointes.
e. Chronic pulmonary disease, including but not limited to: clinically significant chronic obstructive pulmonary disease, interstitial lung disease, pulmonary fibrosis, sarcoidosis.
f. Part B and C only: Hemoglobinopathy, including, but not limited to, thalassemia major
g. 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
h. 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 normal neurological examination is documented in trial files within 6 months of Day 1.
i. History of stroke or transient ischemic attack.
j. History of a medical/surgical condition that resulted in hospitalization within the 3 months prior to enrollment, other than for minor elective procedures.
k. Medical/surgical conditions that may result in a need for hospitalization d