MK-5172/MK-3682 with MK-8742 or MK-8408 in HCV GT3 Infected Subjects

Phase 1

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

• Registration Number: EUCTR2014-003347-35-GB
• Lead Sponsor: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co.,Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2014-09-24
• Study Completion: 2017-05-03
• Last Update Posted: 30 June 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 413

Inclusion Criteria

The following applies to Part A & B unless specified:
1.be =18 years
2.HCV RNA (= 10,000 IU/mL in peripheral blood) at screening.
3. Have documented chronic HCV GT3 (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 at the time of screening with a liver biopsy consistent with chronic HCV infection
4.Be otherwise healthy as determined by the medical history, physical examination, ECG, and clinical lab measurements
5.have liver disease staging assessment as follows:
Absence of cirrhosis defined as follows
•Liver biopsy performed within 24 months of Day 1 of this study •Fibroscan performed within 12 months of Day 1 of this study with a result of =12.5 kPa
•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):
•Liver biopsy performed prior to Day 1 of this study showing cirrhosis (F4)
•Fibroscan performed within 12 months of Day 1 of this study with a result >12.5 kPa
•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
b.Prior virologic failure after treatment with a Peg-IFN/RBV regimen
(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.
7.meet one of the following categories:
-subject is is not of reproductive potential
- 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, and for 90 days after the last dose of study drug by complying with one of the following: (1) practice abstinence OR (2) use (or have their partner use) two forms of acceptable barrier contraception Acceptable methods of contraception are:
•oral contraceptives (Part B and C only)
•intrauterine device
•diaphragm with spermicide
•cervical cap with spermicide (nulliparous women only)
•contraceptive sponge with spermicide (nulliparous women only)
•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 90 days after the last dose of trial drug.
8. understand the study procedures, alternative treatments available, risks involved with the study, and voluntarily agrees to participate
9. provide written informed consent for the trial.
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 and confirmed by a licensed Western blot or

Exclusion Criteria

1. is under the age of legal consent, is mentally or legally incapacitated, has significant emotional problems or has a history of a clinically significant psychiatric disorder which would interfere with the study procedures
2.has evidence of decompensated 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.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.
7.has a history of malignancy =5 years prior to signing informed consent.
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 alchol 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 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
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 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 or anti-arrhythmic agents for cardiac conditions, prolonged ECG QTc interval (>470 ms for males or >480 ms for females by either the Fridericia formula) at the screening visit, 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 C only: Haemoglobinopathy, including but not limited to thalassaemia major.
g.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 Day1.
i.History of stroke or transient ischemic attack.
j.History of a medical/surgical cond

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified