Hepatitis C MedDRA version: 17.1 Level: LLT Classification code 10019751 Term: Hepatitis C virus System Organ Class: 100000004848
Conditions
Interventions
Product Name: MK-5172
Product Code: MK-5172
Pharmaceutical Form: Tablet
INN or Proposed INN: MK-5172
Other descriptive name: MK-5172
Sponsors
Merck Sharp & Dohme Copr., a subsidary of Merck & Co.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. be ? 18 years of age on day of signing informed consent. 2. have HCV RNA (? 10,000 IU/mL in peripheral blood) at the time of screening. 3. have documented chronic HCV GT1 infection (Part C subjects may have GT4 or GT6 infection), 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. have evidence of hepatic cirrhosis with a score on the Child-Pugh scale from 7 to 9 (moderate hepatic insufficiency) at the time of screening and not anticipated to receive a liver transplant within the next 36 weeks (for Arm 1 in Part A, Arm 3 in Part B and Arm 4 in Part C) 5. have no evidence of cirrhosis based on the following (only for Arm 2 in Part A): - 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 ? 9.5 kPa -A FibroSure® (Fibrotest®) score of ? 0.48 and Aspartate Aminotransferase to Platelet Ratio Index (APRI) of ? 1 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® 6. agree (if subject is of reproductive potential) to remain truly abstinent or use (or have their partner use) 2 acceptable methods of birth control from at least 2 weeks prior to Day 1 and continue until at least 6 months after last dose of study drug, or longer if dictated by local regulations. If acceptable by local regulatory agencies, methods of birth control allowed in the study are: intrauterine device (IUD), diaphragm with spermicide, hormonal contraceptives (e.g., birth control pills, transdermal patch, or injectables), contraceptive sponge, female condom, male condom with spermicide, or vasectomy. 7. understand the study procedures, alternative treatments available, risks involved with the study, and voluntarily agrees to participate by giving written informed consent. 8. provide written informed consent for the trial. The subject may also provide consent for Future Biomedical Research. However, the subject may participate in the main trial without participating in Future Biomedical Research. 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 6 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 3
Exclusion criteria
Exclusion criteria: 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, in the opinion of the investigator, would interfere with the study procedures. 2. is co-infected with hepatitis B virus (e.g. HBs Ag positive) or HIV. 3. has previously received direct-acting antiviral therapy for HCV. 4. 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. 5. has cirrhosis and liver imaging within 4 weeks prior to screening showing evidence of hepatocellular carcinoma (HCC), or is under evaluation for HCC. Note: If liver imaging within 4 weeks of screening is not available, imaging is required during screening. 6. is taking or plans to take any of the prohibited medications listed in Section 5 of this protocol or taking herbal supplements, including but not limited, to St. John´s Wort (Hypericum perforatum) within 2 weeks of Day 1. Only silymarin (Milk Thistle, Silybum marianum) is permitted during the trial. 7. 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. 8. has a clinically-relevant drug or alcohol abuse within 12 months of screening. 9. 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 continue throughout treatment and follow up, 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 and continue throughout treatment and follow up, or longer if dictated by local regulations. 10. has any of the following conditions: - Organ transplants (including hematopoietic stem cell transplants) other than cornea and hair. - Poor venous access 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. 11. has any condition or prestudy laboratory abnormality, or history of any illness, which, in the opinion of the investigator, might confound the results of the study or pose additional risk in administering the study drugs to the subject. 12. has a life-threatening SAE during the screening period. 13. has evidence or history of chronic hepatitis not caused by HCV, including but not limited to nonalcoholic steatohepatitis (NASH), drug-induced hepatitis, and autoimmune hepatitis. NOTE: Subjects with history of acute non-HCV-related hepatitis, which resolved > 6 months before study entry, can be enrolled. 14. has
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): The primary efficacy endpoint will be the proportion of CP-B subjects treated with the dose of MK-5172 used in Part C achieving SVR12; Main Objective: (1) Objective: To evaluate the efficacy of MK-5172 in combination with MK-8742 as assessed by the proportion of subjects achieving SVR12 (Sustained Virologic Response 12 weeks after the end of all study therapy), defined as HCV RNA <LLoQ (either TD[u] or TND) 12 weeks after the end of all study therapy. (2) Objective: To evaluate the safety and tolerability of MK-5172 in combination with MK-8742. ; Secondary Objective: (1) Objective: To evaluate the efficacy of MK-5172 in combination with MK-8742 as assessed by the mean improvement in MELD score from baseline (Day 1) to follow-up week 12 in subjects who receive the dose of MK-5172 used in Part C. (2) Objective: To evaluate the efficacy of MK-5172 in combination with MK-8742 as assessed by the proportion of subjects who receive the dose of MK-5172 used in Part C achieving: -SVR4 defined as HCV RNA <25 IU/mL (either TD(u) or TND) 4 weeks after the end of all study therapy. -SVR24 defined as HCV RNA <25 IU/mL (either TD(u) or TND) 24 weeks after the end of all study therapy. SVR = Sustained Virologic Response ;Timepoint(s) of evaluation of this end point: SVR12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: TW2, TW4, TW12, SVR4, SVR12, and SVR24; Secondary end point(s): 1. the mean improvement in MELD scores from baseline (Day1) to follow-up week 12 among CP-B subjects who achieve SVR12 with the dose of MK-5172 used in Part C. 2. the proportion of CP-B subjects treated with the dose of MK-5172 used in Part C achieving SVR4 and SVR24. 3. the proportion of CP-B subjects achieving undetectable (TND) HCV RNA levels and HCV RNA levels < LLoQ at Week 2, Week 4, and Week 12 | — |
Countries
Australia, Canada, Estonia, France, Ireland, Italy, Lithuania, Netherlands, New Zealand, Poland, Spain, United Kingdom, United States
Contacts
Public ContactInvestigación Clínica
Merck Sharp & Dohme de España S.A.
Outcome results
None listed