MK-5172/MK-8742 vs Sofosbuvir/PR in HCV GT1, 4 or 6 Infectio

Phase 1

Conditions: Hepatitis C
Therapeutic area: Diseases [C] - Virus Diseases [C02]
MedDRA version: 17.1Level: LLTClassification code 10019751Term: Hepatitis C virusSystem Organ Class: 100000004848

Registration Number: EUCTR2014-003836-38-ES

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: 256

Inclusion Criteria

1. Be ?18 years of age on day of signing informed consent
2. Weigh ? 40 kg and ?125 kg
3. Have HCV RNA ? 10,000 IU/mL at the time of screening
4. Have documented chronic HCV GT 1, 4 or 6 (with no evidence of non-typeable or mixed genotype) infection:
? Positive for anti-HCV antibody, HCV RNA, or HCV GT 1, 4 or 6 at least 6 months before screening (HCV RNA and HCV genotype must be confirmed by screening lab results), 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)
5. Have liver disease staging assessment as follows:
Cirrhosis is defined as any one of the following [29][30]:
? A liver biopsy performed prior to Day 1 of this trial showing cirrhosis (F4)
? Fibroscan performed within 12 calendar months of Day 1 of this trial showing cirrhosis with result >12.5 kPa [30]*
? 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.)
Absence of cirrhosis is defined as any one of the following:
? Liver biopsy performed within 24 months of Day 1 of this trial showing absence of cirrhosis
? Fibroscan performed within 12 months of Day 1 of this trial with a result of ?12.5 kPa [30]1
? A Fibrosure® (Fibrotest®) score of ?0.48 and Aspartate Aminotransferase to Platelet Ratio Index (APRI) of ?1 during Screening
6. Have an HCV treatment status that is one of the following:
a. Treatment naïve:
? Naïve to all anti-HCV treatment
b. PR treatment experienced:
? peg-IFN/Ribavirin (PR) Null Responder: <2 log10 IU/mL reduction in HCV RNA at Week 12 OR <1 log10 IU/mL decline from baseline at Week 4 and discontinued therapy prior to Week 12
? PR Partial Responder: > 2 log10 IU/mL reduction in HCV RNA by week 12 of treatment, but HCV RNA quantifiable (? LLOQ) at the end of treatment
? Prior PR Relapser: Subject relapsed after completing a prior course of HCV therapy of a dual regimen of PEG-IFN with Ribavirin. (HCV RNA undetectable (?target not detected?) at end of treatment with a Peg-IFN containing regimen, but HCV RNA quantifiable (? LLOQ) during follow-up)
7. Agree to use at least use at least 2 effective non-hormonal methods of contraception1 from at least 2 weeks prior to Day 1 and continue until up to 6 months after last dose of study drug, or longer if dictated by local regulations (for female subject who is of childbearing potential or male subject with female sexual partner who is of childbearing potential).
? If acceptable by local regulatory agencies, methods of birth control allowed in the study are: intrauterine device (IUD), diaphragm with spermicide, contraceptive sponge (nulliparous women only), female condom, male condom with spermicide, vasectomy, and true abstinence: Abstinence2 is in line with the preferred and usual lifestyle of the subject.
? For the purposes of this protocol, a woman of non-childbearing potential is defined as one who has either 1) reached natural menopause (defined as 12 months with no menses without an alternative medical cause), 2) 6 weeks post-surgical bilateral oophorectomy with or without hysterectomy, or 3) bilateral tubal ligation.
? For the purposes of this protocol, a male subjec

Exclusion Criteria

1. Is under the age of legal consent, is mentally or legally incapacitated, has significant emotional problems at the time of pre-trial screening visit or expected during the conduct of the trial or has a history of a clinically significant psychiatric disorder which, in the opinion of the investigator, would interfere with the trial procedures.
2. Subject is not, in the opinion of the investigator, an appropriate candidate for only 12 weeks of PR-based therapy.
NOTE: All subjects in this trial will only receive 12 weeks of treatment. Based on the SOF EU label, investigators should consider the following and decide if a subject is appropriate for enrollment. ?Consideration should be given to potentially extending the duration of therapy beyond 12 weeks and up to 24 weeks; especially for those subgroups who have one or more factors historically associated with lower response rates to interferon-based therapies (e.g. advanced fibrosis/cirrhosis, high baseline viral concentrations, black race, IL28B non CC genotype, prior null response to peg interferon alfa and ribavirin therapy)? [31].
3. 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. For cirrhotics, subjects that are Child-Pugh Class B or C or who have a Pugh-Turcotte (CPT) score >6, must be excluded.
NOTE: To calculate the Child-Pugh score, refer to the following website: http://www.mdcalc.com/child-pugh-score-for-cirrhosis-mortality.
4. Is co-infected with hepatitis B virus (e.g., HBsAg positive) or HIV.
5. 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.
6. Has cirrhosis and liver imaging within 6 months of Day 1 showing evidence of hepatocellular carcinoma (HCC) or is under evaluation for HCC.
NOTE: If liver imaging within 6 months of Day 1 is not available, imaging is required during screening.
7. Is taking or plans to take any of the prohibited medications listed in Section 5.5.1 of this protocol or taking herbal supplements, including but not limited to:
a. Significant inducers or inhibitors of CYP3A4 substrates 2 weeks prior to start of study medications (Day 1) (see section 5.5.1-Prohibited Medications, for further guidance);
b. Herbal supplements, including, but not limited to, St. John?s Wort (Hypericum perforatum) within 2 weeks of Day 1.
8. 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 trial.
9.Has pre-existing psychiatric condition(s), including but not limited to:
a. Current moderate or severe depression.
b. History of depression associated with any of the following:
i. Hospitalization for depression.
ii. Electroconvulsive therapy for depression.
iii. Depression that resulted in a prolonged absence from work and/or significant disruption of daily functions.
c. Suicidal or homicidal ideation and/or attempt.
d. History of severe psychiatric disorders (including but not limited to schizophrenia, psychosis, bipolar disorder, post-traumatic stress disorder or mania).
e. Past history or current use of lithium.
f. Past histo