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MK-5172 in Combination with MK-8742 in subjects with HCV and Chronic Kidney Disease

Phase 1
Conditions
Hepatitis C
MedDRA version: 17.0Level: LLTClassification code 10019183Term: HCVSystem Organ Class: 100000004848
Therapeutic area: Diseases [C] - Virus Diseases [C02]
Registration Number
EUCTR2013-003858-25-EE
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
220
Inclusion Criteria

Be =18 years of age on day of signing informed consent.

Have documented chronic (at least 6 months) HCV GT1 infection (with no evidence of non typable or mixed genotypes) :
- Positive for anti-HCV antibody, HCV RNA, or an HCV genotype
- HCV RNA (= 10,000 IU/mL in peripheral blood)

Subjects with or without cirrhosis may be enrolled into this study. All subjects must have one of the below liver disease staging assessments as follows:
•Liver biopsy performed within 24 months of Day 1 (if subject is cirrhotic then there is no time restriction on biopsy)
•Fibroscan performed within 12 months of Day 1
•A FibroSure® (Fibrotest®) and Aspartate Aminotransferase to Platelet Ratio Index (APRI) (APRI is automatically calculated by central laboratory) during Screening.
In the absence of a definitive diagnosis of presence or absence of cirrhosis by the above critieria, a liver biopsy is required. Liver biopsy results supersede the results obtained by Fibroscan or FibroSure®.

Have an HCV treatment status that is one of the following:
Treatment naïve: Naive to all anti-HCV treatment
Prior IFN or PEG-IFN + Ribavirin Treatment failures: Null responders, Partial responders, Relapsers
P/R Intolerant: Subjects were intolerant to a prior IFN or PEG-IFN ± Ribavirin regimen, Subjects discontinued treatment prematurely and were therefore unable to complete a full course of therapy because of drug-related toxicity.

Have Chronic Kidney Disease defined as:
Subjects with GFR =29 who are non-dialysis dependent (NDD) or have been on hemodialysis (HD) for at least 3 months (including subjects awaiting kidney transplant and subjects with failed kidney transplants no longer on immunosuppressant therapy).

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 110
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 110

Exclusion Criteria

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.

Evidence of decompensated liver disease manifested by the presence of or history of ascites, gastric or variceal bleeding, hepatic encephalopathy or other signs or symptoms of advanced liver disease.

Is on peritoneal dialysis for management of Kidney disease

In the opinion of the investigator the subject has a high likelihood of
receiv ing a renal transplant during the study treatment period (up to 24 weeks from Day 1).

Is coinfected with hepatitis B virus (e.g. HBsAg positive) or HIV.

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 has evidence of hepatocellular carcinoma (HCC) or is under evaluation for other active or suspected malignancy.

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.

Has a clinical diagnosis of substance abuse of the following specified drugs within specified timeframes:
- alcohol, intravenous drugs, inhalational (not including marijuana), psychotropics, narcotics, cocaine use, prescription or over-the-counter drugs: within 1 year of the screening visit or, if shorter is judged by the investigator to be capable of complying with study procedures, OR
NOTE: Subjects receiving opiate agonist substitution therapy are not excluded from the study if, in the opinion of the investigator, the subject is capable of complying with all study procedures - history of marijuana use is deemed excessive by a physician investigator or is interfering with the subject's daily function. If subject's marijuana use is not deemed excessive and does not interfere with daily function, subject must be instructed to discontinue any current use of recreational marijuana prior to entry into trial and throughout the trial period.

Female subject who is pregnant or breast-feeding, or expecting to conceive or donate eggs from Day 1 through 14 days after the last dose of study drugs, or longer if dictated by local regulations or male subject who is expecting to donate sperm from Day 1 through 14 days after the last dose of study drugs, or longer if dictated by local regulations.

Has any of the following conditions:
- Organ transplants (including hematopoietic stem cell transplants) other than kidney, cornea and hair.
- Poor venous access in non-dialysis patients that precludes routine peripheral blood sampling required for this trial.
- Subject with a history of gastric surgery (e.g., stapling, bypass) or subject with a history of malabsorption disorders (e.g., celiac sprue disease).
- Any medical condition requiring, or likely to require, chronic systemic administration of corticosteroids during the course of the trial.
- Has uncontrolled or poorly controlled hypertension including but not limited to hypertensive emergency or hospitalization for hypertension in preceding 3 months.
- Diagnosed with a significant cardiovascular disorder (e.g. MI or unstable angina)

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Secondary Outcome Measures
NameTimeMethod
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