| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
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| E.1.1.1 | Medical condition in easily understood language |
| A viral infection affecting the liver |
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| E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 17.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10019751 |
| E.1.2 | Term | Hepatitis C virus |
| E.1.2 | System Organ Class | 100000004848 |
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| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
(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.
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| E.2.2 | Secondary objectives of the trial |
(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
(3) Objective: To evaluate the efficacy of MK-5172 in combination with MK-8742 as assessed by the proportion of CP-B subjects who receive the dose of MK-5172 used in Part C achieving undetectable (TND) HCV RNA and HCV RNA < LLoQ at Week 2, 4 and 12.
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| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
| Merck will conduct Future Biomedical Research on DNA (blood) specimens collected during this clinical trial. Such research is for biomarker testing to address emergent questions not described elsewhere in the protocol (as part of the main trial) and will only be conducted on specimens from appropriately consented subjects. The objective of collecting specimens for Future Biomedical Research is to explore and identify biomarkers that inform the scientific understanding of diseases and/or their therapeutic treatments. The overarching goal is to use such information to develop safer, more effective drugs, and/or to ensure that subjects receive the correct dose of the correct drug at the correct time |
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| E.3 | Principal 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. 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.
6. understand the study procedures, alternative treatments available, risks involved with the study, and voluntarily agrees to participate by giving written informed consent.
7. 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. |
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| E.4 | Principal 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 exclusionary laboratory values as listed below:
Note: If any of the laboratory exclusion criteria below are met, the site may have the abnormal value retested one time.
Exclusionary Laboratory Values
Laboratory Assessment Cirrhotic (CP-B)
Hemoglobin <9.5 g/dL for both male and female subjects
Creatinine Clearance <30 mL/min
Platelets < 30 x 103/μL
Serum Albumin < 2.2 g/dL
INR >2.3
Total Bilirubin > 3.0 mg/dL
HbA1c >10%
ALT >5 x ULN
AST >5 x ULN
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| E.5 End points |
| E.5.1 | 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 |
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
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| E.5.2 | Secondary end point(s) |
The secondary efficacy endpoints are:
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
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| TW2, TW4, TW12, SVR4, SVR12, and SVR24 |
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| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 1 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 20 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Australia |
| Canada |
| Estonia |
| France |
| Ireland |
| Italy |
| Lithuania |
| Netherlands |
| New Zealand |
| Poland |
| United Kingdom |
| United States |
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| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial days | 26 |
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