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.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
•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.
•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 |
Part A
1) To evaluate the efficacy of MK-5172 in combination with MK-8742 as assessed by the proportion of subjects achieving: SVR24 (Sustained Virologic Response 24 weeks after the end of all study therapy), defined as HCV RNA <LLOQ (either TD(u) or TND) 24 weeks after the end of all study therapy.
Part B
1) To evaluate the durability of SVR and the incidence of detectable HCV
RNA, classified as either relapse or reinfection, over a three year follow-up period
following the treatment/follow-up as defined in Part A .
2) To characterize the HCV virus detected during the Part A treatment and
follow-up periods and as well as in the Part B 3-year follow-up period including:
a. To describe the presence of baseline viral resistance-associated variants
(RAVs)
b. To describe treatment emergent RAVs
c. To determine reinfection versus relapse |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Part A:
•You are greater than or equal to 18 years of age.
•You have chronic genotype 1, 4, 5, or 6 Hepatitis C virus.
•You must be on opiate substitution therapy (OST), have kept at least 80% of scheduled appointments while on OST, and not missed any scheduled appointments between screening and study entry
•You have had a liver biopsy, Fibroscan, or Fibrotest to check for cirrhosis or no cirrhosis.
•You are treatment naïve to all HCV treatment
•You may be co-infected with HIV
Part B:
- You have received at least one dose of MK-5172 in combination with MK-8742 as detailed in
Part A.
- You understand the study procedures, alternative treatments available, risks involved with the
study, and voluntarily agree to participate by giving written informed consent. |
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E.4 | Principal exclusion criteria |
Part A:
•You have signs of decompensated liver disease.
•You are coinfected with Hepatitis B virus.
•You have signs of hepatocellular carcinoma or history of malignancy.
•You are taking or plan to take any medication not allowed for this study.
•You have a history of, or signs of, chronic hepatitis not caused by hepatitis C virus.
•You have an exclusionary laboratory value
•If you have HIV, you use HIV drugs other than a dual NRTI backbone of tenofovir or abacavir and either emtricitabine or lamivudine PLUS raltegravir [or dolutegravir or rilpivine]
•You have a history of opportunistic infection in the preceding 6 months prior to screening.
Part B:
- You are mentally or legally incapacitated, have significant emotional problems at the time of
pre-study screening visit or expected during the conduct of the study or have a history
of a clinically significant psychiatric disorder which, in the opinion of the
investigator, would interfere with the study procedures.
- You have a medical condition or personal circumstance which, in the opinion of
the investigator and/or Sponsor, places you at unnecessary risk through
continued participation in the trial or does not allow you to adhere to the
requirements of the protocol.
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E.5 End points |
E.5.1 | Primary end point(s) |
The SVR12 rate of subjects enrolled. |
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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) |
Part A: The SVR24 rate of subjects enrolled.
Part B: primary measurement is plasma HCV RNA, collected every 6 months to evaluate long term durability of SVR and incidence of reinfection in subjects with detectable HCV RNA. |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
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) | No |
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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 |
Australia |
Belgium |
Canada |
France |
Germany |
Greece |
Ireland |
Israel |
Italy |
Lithuania |
Malaysia |
Netherlands |
New Zealand |
Norway |
Romania |
Spain |
Taiwan |
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 | 3 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 3 |