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 |
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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 | 20.0 |
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 |
Adult Population
1. To evaluate the durability of response in subjects who achieved SVR24 in the prior treatment study and at the time of entry into PN017 were HCV ribonucleicacid (RNA) lower limit of quantification (LLoQ) (either target not detected [TND] or target detected, unquantifiable [TD(u)]).
2. To evaluate the presence of treatment-emergent antiviral resistance to NS3/4A, NS5A and/or NS5B regions, (as applicable) and determine if there is a reversion to wild-type pattern within the 3-year time frame of this long-term followup study (or 5-year time frame for subjects from PN052) in subjects with virologic failure in the prior treatment study and with HCV RNA ≥1000 IU/mL in Protocol 017.
3. Objective: To evaluate the long-term safety.
Pediatric Population
1. Objective: To evaluate the persistence of treatment-emergent antiviral resistance to NS3 and NS5A regions within the 3-year time frame of this long-term follow-up study. |
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E.2.2 | Secondary objectives of the trial |
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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 |
Inclusion criteria apply to both adult and pediatric populations unless otherwise noted.
1. Subjects previously participated in a HCV treatment study and received GZR in the treatment regimen.
2. Subject must enroll in PN017 (Visit 1) within 3 months of the last study visit (e.g. follow-up week [FW] 24) of the prior treatment study in which they received a GZR containing regimen.
3. Subject is male or female 3 years of age or older on day of signing informed consent/assent.
4. Subject or subject’s legally acceptable representative provides written informed consent (or written informed assent where applicable). Subjects who have consented for the study may also provide consent/assent for Future Biomedical Research (FBR). However, the subject may participate in PN017 without consenting/assenting for FBR.
5. Starting with AM 03: Adult subject must have received at least 1 dose of a GZRcontaining regimen in the prior treatment study and identified as having failed therapy in that study.
6. Pediatric subject must have received at least 1 dose of a GZR-containing regimen and experienced virologic failure with 1 or more associated treatment-emergent RASs at FW12 in PN079. |
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E.4 | Principal exclusion criteria |
Exclusion criteria apply to both the adult and pediatric populations.
1. Adult subjects: In the opinion of the investigator, subject is mentally or legally incapacitated at entry into PN017.
Pediatric subjects: The subject has significant emotional problems or a clinically significant psychiatric disorder that may interfere with participant treatment, assessment, or compliance with the protocol.
2. Subject has received HCV therapy after completion of the prior treatment study and before entry into PN017.
3. Starting with AM 03: subjects who failed therapy due to re-infection, defined as:
- an HCV RNA sample with a different genotype than the baseline genotype in the prior treatment study, or
-an HCV RNA sample determined to be reinfection by phylogenetic analysis with comparison to the baseline sequence in the prior treatment study.
4. Starting with AM 03: subjects who failed therapy in the prior treatment study and received retreatment with HCV therapy |
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E.5 End points |
E.5.1 | Primary end point(s) |
For Adults Patients:
A primary efficacy endpoint is the durability of long-term SVR which will be evaluated based upon the time to viral relapse. Viral relapse is defined as any subject who has confirmed HCV RNA > or = LLoQ and was previously <LLoQ at end of follow-up in previous trial. Relapse would be indicated so long as this was the same genotype of the virus seen in the parent protocol (eg. not a new infection or re-infection). Time to relapse is defined as the time from last dose of study therapy taken in previous trial until the date where HCV RNA is > or = LLoQ. The percentage of subjects who remain HCV RNA < LLoQ during the course of this study will also be estimated.
In subjects with HCV RNA > or = 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.
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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) |
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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 | 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 | 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. |
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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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 109 |
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 |
Canada |
France |
Germany |
Israel |
Italy |
New Zealand |
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 | 10 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 10 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |