E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with chronic HBeAg-negative hepatitis B with a stable oral antiviral treatment (not containing telbivudine) and a fully suppressed viral load for at least 12 months (below limit of detection in conventional HBV-PCR assays, i.e. <116 IU / ml). |
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E.1.1.1 | Medical condition in easily understood language |
Patients with chronic hepatitis B. |
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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 | LLT |
E.1.2 | Classification code | 10019738 |
E.1.2 | Term | Hepatitis B positive |
E.1.2 | System Organ Class | 100000109834 |
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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 |
The primary objective of the trial is to investigate whether the add-on of pegylated interferon alfa-2a to a continued treatment with nucleos(t)ide analogues increases the percentage of patients who have significant decrease (≥1log10) of HBs-antigen after 48 weeks. |
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E.2.2 | Secondary objectives of the trial |
• To evaluate safety and tolerability of pegylated interferon alfa-2a when combined with tenofovir, entecavir, lamivudine, adefovir, or a combination of those:
- Adverse events
- Vital signs, physical examination
- Laboratory test abnormalities
- Laboratory test value changes over time
•To identify biological variables predicting HBs antigen decrease:
- viral genotype
- kinetic of HBs antigen level
• To determine the effect of pegylated interferon on frequency and functional properties of HBV-specific cytotoxic and regulatory T-cells in responder and nonresponder patients
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Chronic hepatitis B, HBe antigen negative
• Treatment with a stable oral antiviral treatment (not containing telbivudine) and a fully suppressed viral load for at least 12 months (below limit of detection in conventional HBV-PCR assays, i.e. <116 IU / ml).
• 18-70 yrs
• Willingness and ability to give informed consent and to follow study procedures
• willingness to use adequate contraception
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E.4 | Principal exclusion criteria |
• HBe antigen positive Hepatitis B
• Co-infection with HCV, HDV or HIV – as based on positive serology or PCR
• Ongoing antiviral treatment with Telbivudine
• Contraindications against treatment with pegylated interferon, e.g. severe depression, epilepsy, autoimmune diseases, pregnancy, leukocytopenia or thrombocytopenia at screening, etc.
• Preexisting polyneuropathy
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the objective response after 48 weeks of therapy. The response is defined as a confirmed reduction of ≥1log10 in HBs antigen compared to baseline. |
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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) |
1. Decline of quantitative HBs antigen at week 12 and 24
2. Rate of patients with at least 10% HBs antigen loss at week 24 compared to baseline
3.HBsAg seroconversion defined as percentage of subjects who become HBsAg negative and anti-HBs positive during the observation period
4.Safety and tolerability of pegylated interferon alfa-2a when added to a continuing treatment with tenofovir, entecavir, lamivudine, adefovir, or a combination of those: Analysis of adverse events and laboratory data.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
add 1. at week 12 and 24
add 2. at week 24
add 3. at week 1 - 72
add 4. at week 1 - 72
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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 | 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 | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
- Immune monitoring
- Bioinformatic analysis of genetic markers
- Other biomarkers |
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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 | 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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Patients of the controll group continue their basic Nucleos(t)ide treatment |
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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 | 16 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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 | 0 |
E.8.9.1 | In the Member State concerned months | 24 |
E.8.9.1 | In the Member State concerned days | 0 |