E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
CHRONIC HEPATITIS B VIRUS INFECTION |
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E.1.1.1 | Medical condition in easily understood language |
CHRONIC HEPATITIS B 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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008910 |
E.1.2 | Term | Chronic hepatitis B |
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 |
To assess rates of the following clinical outcomes:
1) malignant neoplasms (overall and non-HCC, in each case including carcinoma in situ [CIS] but excluding non-melanoma skin cancer, and HCC);
2) liver-related events of HBV disease progression;
3) mortality (all cause, liver-related) |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Signed written informed consent
2) Chronic HBV infection, as confirmed by the investigator
3) HBV nucleoside/tide-naive or -experienced
4) Patients who, in the opinion of the investigator, are appropriate for initiating or modifying their HBV therapy and who are appropriate for a treatment regimen comprised of nucleoside/tide monotherapy with either ETV or another standard of care HBV nucleoside/tide analogue
5) Age 16 and older or minimum age required in a given country
6) Male or female
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E.4 | Principal exclusion criteria |
• Sex and Reproductive Status
1) Women who are pregnant or breastfeeding
2) Women with a positive pregnancy test on enrollment or prior to randomization
• Target Disease Exceptions
3) Patients who, in the opinion of the investigator, are expected to have a liver transplant-free survival of less than one year
15) Patients who, in the opinion of the investigator, are virologically controlled on their current HBV treatment regimen and clinically responding to treatment, unless the regimen needs to be modified for medication intolerance.
• Medical History and Concurrent Diseases
4) Coinfection with HIV, as confirmed by investigator
5) History of malignant neoplasm(s), including HCC and CIS, but excluding nonmelanoma skin cancers. The presence of current malignancy, including HCC, is to be excluded by screening and evaluation practices standard in the country of enrollment.
6) History of dysplastic liver nodules
16) Patients with chronic renal insufficiency, defined as a creatinine clearance < 50 ml/min who do not have either of the following means of dose reducing ETV:
a.) an approved country-specific ETV label which includes the extended interval
ETVdose modification method
and/or
b.) an approved country specific label for the ETV oral solution AND access to the
oral solution.
• Allergies and Adverse Drug Reactions
7) Known history of allergy to nucleoside/tide analogues
• Prohibited Therapies and/or Medications
8) Prior or current treatment with ETV
9) An investigator proposed study regimen which will include only IFN-alfa
10) An investigator proposed study regimen of combination (two or more) HBV nucleoside/tide analogue therapy
11) An investigator proposed study regimen which will include TDF, unless TDF is an approved therapy for HBV in the patient’s country
12) An investigator proposed study regimen which will include LdT, unless LdT is an approved therapy for HBV in the patient’s country
13) An investigator proposed study regimen which will include one or more investigational agents for the treatment of HBV
• Other Exclusion Criteria
14) Prisoners or patients who are compulsorily detained |
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E.5 End points |
E.5.1 | Primary end point(s) |
Clinical Outcome Measures:
• Non-HCC malignant neoplasm rates (including CIS, but excluding non-melanoma
skin cancer)
• HCC rates
• Overall malignant neoplasm rates (including CIS, but excluding non-melanoma skin
cancer)
• Mortality (all cause, liver-related)
• Rates of liver-related manifestations of HBV disease progression rates, defined as:
− progression from non-cirrhotic liver status to cirrhosis
− progression from compensated to decompensated cirrhosis (e.g.
gastroesophageal variceal bleeding, ascites, hepatic encephalopathy,
hepatorenal syndrome)
− progression from decompensated cirrhosis (e.g. history or presence at enrollment
of one/more manifestations of decompensated cirrhosis) to worsening of
decompensated cirrhosis (e.g. new, recurrent or ongoing event of
decompensated cirrhosis following enrollment)
− development of HCC
− liver-related death
− decision to list for liver transplantation |
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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 | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
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 | Yes |
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) | Yes |
E.8.2.2 | Placebo | No |
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
| 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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 72 |
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 |
Brazil |
Canada |
China |
Colombia |
Czech Republic |
France |
Germany |
Greece |
India |
Italy |
Korea, Republic of |
Mexico |
Philippines |
Poland |
Portugal |
Romania |
Russian Federation |
Singapore |
Spain |
Taiwan |
Turkey |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |