| 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 |
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| E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
| MedDRA Classification |
| 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)To evaluate the efficacy of the combination regimen of MK-5172, MK-3682 and MK-8408 with or without ribavirin as assessed by the proportion of subjects in each arm 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 the combination regimen of MK-5172, MK-3682 and MK-8408 with or without ribavirin to subjects in each arm.
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| E.2.2 | Secondary objectives of the trial |
(1) To evaluate the efficacy of the combination regimen of MK-5172, MK-3682 and MK-8408 with or without ribavirin as assessed by the proportion of subjects in each arm achieving SVR4 (Sustained Virologic Response 4 weeks after the end of all study therapy)
(2) Objective: To evaluate the efficacy of the combination regimen of MK-5172, MK-3682 and MK-8408 with or without ribavirin as assessed by the proportion of subjects in each arm achieving SVR24 (Sustained Virologic Response 24 weeks after the end of all study therapy)
(3) Objective: Among HIV-1 co-infected patients, to evaluate the proportion of subjects who develop HIV-1 virologic failure (HIV-1 RNA 200 copies/mL, confirmed on two consecutive tests at least 2 weeks apart, in subjects compliant with their HIV antiretroviral therapy
(4) Objective: Among HIV-1 co-infected patients, to evaluate the effect of the study regimens on CD4 + T-cell counts.
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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.HCV RNA (≥ 10,000 IU/mL in peripheral blood) at the time of screening.
3.have documented chronic HCV GT1 or HCV GT3 infection (with no evidence of non-typeable or mixed genotype)
4.Have documented virologic relapse after treatment with one of the following properly administered direct-acting antiretroviral (DAA) regimens either by approved dosage and duration or by completion of a clinical trial :
GT1:
•SOF/LDV ± RBV
•MK-5172/MK-8742 ± RBV
GT3:
•SOF + RBV
•SOF + PR
•SOF + DCV ± RBV
•SOF/LDV ± RBV
5.Have liver disease staging assessment for Absence of cirrhosis or Compensated cirrhosis as defined in the protocol
6.Can be HIV co-infected as documented as requested by protocol
7.HIV co-infected subjects must either not be on antiretroviral therapy(ART); or have well controlled HIV on ART
8.meet one of the following categories:
a.The subject is a male who is not of reproductive potential, defined as a male who has azoospermia (whether due to having had a vasectomy or due to an underlying medical condition).
b.The subject is a female who is not of reproductive potential, defined as a female who either: (1) is postmenopausal (defined as at least 12 months with no menses in women ≥45 years of age) and have a documented follicle stimulating hormone (FSH) level in the postmenopausal range at pretrial (screening); (2) has had a hysterectomy and/or bilateral oophorectomy, bilateral salpingectomy, or bilateral tubal ligation/occlusion at least 6 weeks prior to screening; OR (3) has a congenital or acquired condition that prevents childbearing.
c.The 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, for 6 months after taking the last dose of study drug if taking a ribavirin-containing regimen (or longer if dictated by local regulations), 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 contraception during heterosexual activity. Acceptable methods of contraception are outlined in the protocol
Refer to protocol for a complete list
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| E.4 | Principal exclusion criteria |
1.Under the age of legal consent
2.did not complete their prior DAA therapy due to intolerance to the DAA regimen or who discontinued the DAA regimen for reasons other than virologic failure (e.g., non-compliance, lost to follow-up, withdrew consent).
NOTE: The trial is limited to those who have documented virologic relapse with a properly administered DAA regimen.
3.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.
4.For cirrhotics, subjects that are Child-Pugh Class B or C or who have a Pugh-Turcotte (CPT) score >6, must be excluded. NOTE: To calculate the Child-Pugh score, refer to the following website: http://www.mdcalc.com/child-pugh-score-for-cirrhosis-mortality.
5.is coinfected with hepatitis B virus (e.g. HBsAg positive).
6.HIV subjects has a history of opportunistic infection
7.History of malignancy within past 5 years; hepatocellular carcinoma under evaluation
8.Currently taking prohibited medication
9.Is currently participating or has participated in a study with an investigational compound within 30 days prior to study start
10.Is a female and is pregnant or breast-feeding, or expecting to conceive or donate eggs from Day 1 through at least 6 months after last dose of study drug, or longer if dictated by local regulations or is a male whose female partner(s) is/are pregnant
11.Is a male subject who is expecting to donate sperm or planning to impregnate female partner(s) from Day 1 through at least 6 months after last dose of study drug, or longer if dictated by local regulations.
Refer to protocol for a complete list of exclusion criteria
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| 1) Proportion of subjects achieving SVR12. |
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| 12 weeks after the end of treatment |
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| E.5.2 | Secondary end point(s) |
1) The proportion of subjects achieving SVR4
2) The proportion of subjects achieving SVR24.
3) The proportion of subjects who develop HIV-1 virologic failure during protocol therapy for HIV co-infected population;
4) Change from baseline in CD4+ T-cell counts for HIV co-infected population.
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| 1) 4 weeks after the end of treatment 2) 24 weeks after the end of treatment |
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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 | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | Yes |
| 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) | No |
| 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 | No |
| 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.8.3 |
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 | 19 |
| 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 |
| France |
| Germany |
| Spain |
| Sweden |
| 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 | 1 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 21 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 21 |
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