E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hepatitis C Virus Infection (HCV) |
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E.1.1.1 | Medical condition in easily understood language |
Hepatitis C Virus Infection |
|
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 | 18.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10019744 |
E.1.2 | Term | Hepatitis C |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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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. To evaluate the durability of SVR in subjects who remained HCV RNA
<25 IU/mL throughout the follow-up period of the treatment protocol and did not
start any new HCV therapy between the end of the previous protocol and entry in this
study.
2. To evaluate the presence of antiviral resistance to MK-5172 and
determine if there is a reversion to a wild-type pattern within the 3 or 5 year timeframe
if subjects were from PN 052 or PN 059) of this long-term follow-up study.
3. To evaluate the long term safety of MK-5172. |
|
E.2.2 | Secondary objectives of the trial |
Exploratory objectives
1. To assess liver function using the MELD and/or Child-Pugh scores.
2. To assess chronic kidney disease (CKD) status by assessing change in eGFR in patients from parent Protocol 052.
3. To assess complication of CKD by recording new onset diabetes, cryoglobulinemia, cardiovascular disease, and/or neurologic disorders (such as stroke) in patients from parent Protocol 052.
4. To assess health outcomes by recording the occurrence of variceal bleeding, ascites, spontaneous bacterial peritonitis, encephalopathy, hepatorenal syndrome, hepatocellular carcinoma, liver/kidney transplantation, graft rejection in patient who have undergone liver/kidney transplantation. |
|
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. HCV infected subjects who previously participated in an MK-5172 protocol and received at least one dose of MK-5172.
2. Subject must enroll (Visit 1) within one year of the treatment portion of their previous MK-5172 protocol.
3. Subject must be ≥ 18 years of age and willing to give written informed consent.
4. Subjects, who have consented for the trial, 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 |
In the opinion of the investigator, if a subject is mentally or legally incapacitated at entry, the subject may be excluded. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy Endpoints
A primary efficacy endpoint is the persistence of SVR which will be evaluated based upon the time to viral relapse. Viral relapse is defined as any subject who has HCV RNA ≥ 25 IU/mL and was previously <25 IU/mL after end of treatment in previous trial (see Section 2.5). Time to relapse is defined as the time from last dose of therapy taken in previous trial until the date where HCV RNA is ≥25 IU/mL. The percentage of subjects who remain HCV RNA <25 IU/mL during the course of this study will also be evaluated.
In subjects with HCV RNA ≥1000 IU/mL at entry or during the study period, HCV sequence analysis will be performed to evaluate the presence of RAVs and the persistence of RAVs over time.
Safety Endpoints
Safety and signs of disease progression are assessed for all subjects by physical
examination, drug-related serious adverse events, events of clinical interest, any AEs
related to protocol-specified procedures (blood draw), and laboratory tests. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
- To evaluate the presence of antiviral resistance to MK-5172 and determine if there is a reversion to a wild-type pattern within the 3 or 5 year timeframe.
- To evaluate the long term safety of MK-5172, within the 3 or 5 year timeframe. |
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
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 | 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 | Yes |
E.8.1.7.1 | Other trial design description |
Long term follow-up study; no therapy is being provided. |
|
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 | 120 |
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 |
Argentina |
Australia |
Austria |
Belgium |
Canada |
Czech Republic |
Denmark |
Estonia |
Finland |
France |
Germany |
Greece |
Hungary |
Israel |
Italy |
Lithuania |
Netherlands |
New Zealand |
Norway |
Poland |
Puerto Rico |
Romania |
Spain |
Sweden |
Switzerland |
Turkey |
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 | 4 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 10 |
E.8.9.2 | In all countries concerned by the trial years | 7 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 10 |