E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic hepatitis B |
Epatite B cronica |
|
E.1.1.1 | Medical condition in easily understood language |
Chronic Hepatitis B |
epatite B cronica |
|
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 determine whether add-on of peg-IFN-a to an ongoing effective nucleos(t)ide therapy achieve higher rates of seroconversion in CHB patients. |
Determinare se l’aggiunta di Peg-IFN-α-2a ad un trattamento efficace di lunga durate con analoghi nucleos(t)idici determini un maggior tasso di sieroconversione di HBeAg e HBsAg in soggetti con CHB, rispetto a coloro che proseguono con la monoterapia con NUCs. |
|
E.2.2 | Secondary objectives of the trial |
To investigate the the immunomodulatory action of IFNα, particularly on the host innate response through the analysis of the mechanisms involved in the restoration of NK cell effector functions in the “add-on” strategy described above. |
Studiare l’effetto immunomodulante della strategia “add-on” con Peg-IFN sulla risposta innata (NK, NKT) e specifica (T CD8+). Considerando i differenti effetti immunologici dei NUCs e dell’IFNα è atteso un cambiamento dei parametri relativi alla conta e funzione delle cellule NK, NKT, e T CD8+. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
age 18-65 years
HBsAg positivity
treatment with NUCs for at least 2 years;
compensated liver disease;
Hb > 12 g/dl
WBC > 3000/mm3
PLT >100000
ANA, AMA, ASMA, LKM-Ab negativity
HCV-Ab and HIV-Ab negative;
Signed informed consent |
età compresa tra i 18 e i 65 anni
HBsAg positività
Trattamento da almeno due anni con NUCs
malattia epatica compensata che soddisfi i seguenti criteri:
emoglobina > 12 g/dl
WBC > 3000/mm3
Piastrine >100000
negatività degli autoanticorpi (ANA, AMA, ASMA, LKM, anticorpi antitireoglobulina e antimicrosomi tiroidei)
HCV-Ab e HIV-Ab negativi
In entrambi i sessi l’impegno a non procreare per tutta la durata del trattamento e per 6 mesi dopo la sospensione.
Sottoscrizione del consenso informato scritto
|
|
E.4 | Principal exclusion criteria |
HCV or HIV coinfection;
Pregnancy:
Other liver diseases besides chronic hepatitis B fuori dell’epatite B;
decompensated liver disease;
Autoimmunity;
Major depression
hypersensitivity to Pegylated interferon
Uncontrolled pilepsy |
coinfezione con HCV o HIV
Gravidanza e allattamento
altre cause di malattia epatica al di fuori dell’epatite B (abuso alcolico, epatiti autoimmuni, emocromatosi, epatopatia da farmaci)
malattia epatica con segni di scompenso ascitico, biochimico o con segni di encefalopatia.
Patologie immunomediate (LES, anemia emolitica autoimmune, psoriasi)
Depressione maggiore con idee suicide
Ipersensibilità a interferone
Convulsioni non controllate |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Loss of HBsAg and/or HBeAg |
Perdita di HBsAg o di HBeAg |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline-week12-week24-week48 |
Al tempo basale, a 12-24 e 48 settimane di tratatmento. |
|
E.5.2 | Secondary end point(s) |
Sustained virological response or therapy suspension at the end of 48 weeks of treatment. |
Raggiungimento di una risposta virologica sostenuta (sieroconversione ad anti-HBeAg o anti-HBsAg) o sospensione della terapia con Peg-IFN-α alla fine delle 48 settimane previste. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
12-24-48-weeks |
12-24-48 settimane |
|
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 | No |
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 | No |
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) | 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 | 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) | 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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |