MK-5172/MK-3682 with MK-8742 or MK-8408 in HCV GT1 and GT2 Infected Subjects
- Conditions
- Chronic Hepatitis C infected patientTherapeutic area: Diseases [C] - Virus Diseases [C02]
- Registration Number
- EUCTR2014-003304-73-GB
- 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
- Not specified
- Target Recruitment
- 442
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 GT1a, GTb or GT2 (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, 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 barrier contraception during heterosexual activity. Acceptable methods of contraception are:
• oral contraceptive (Part B and C only)
• 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 (only for women who have not previously given birth)
• contraceptive sponge with spermicide (only for women who have not previously given birth)
• male condom with spermicide or female condom with spermicide (cannot be used together)
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.
8. understand the study procedures, alternative treatments ava
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 (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.co-infected 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 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 from 2 weeks prior to Day 1 through 2 weeks after the study drug treatment period.
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 through at least 6 months after the last dose of study drug, or longer if dictated by local regulations OR is a male subject who is expecting to donate sperm or planning to impregnate female partner(s) from at least 2 weeks prior to day 1 through at least 6 months after the last dose of study drug, or longer if dictated by local regulations.
13. Parts B and C only: is a male whose female partner(s) is/are pregnant (this is a contraindication for ribavirin use)
14. has any of the following conditions:
a.Organ transplants (including haematopoietic 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.
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: Haemoglobinopathy, including, but not limited to. thalassaemia major
g. CNS trauma requiring intubation, intracranial pressure monitoring, brain meningeal or skull surgery, o
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method