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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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008910 |
E.1.2 | Term | Chronic hepatitis B |
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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 investigate sustained HBeAg response to peg-interferon alfa-2b in chronic HBeAg-positive hepatitis B patients who are pretreated with nucleos(t)ide analogues, thereby lowering viral load |
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E.2.2 | Secondary objectives of the trial |
· Determine the effect of PEG-IFNa on NK cell function and induction HBV-specific immunity in patients with relatively low viral load. · Determine whether NK cell function and HBV-specific T cell response can be predictive for sustained off-treatment effective HBV-specific immunity
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
· Chronic hepatitis B (HBsAg positive > 6 months) · HBeAg positive, anti-HBe negative within one month prior to initiation of peg-interferon alfa-2b · HBV DNA < 2000 IU/ml during nucleos(t)ide analogue treatment within one month prior to initiation of peg-interferon alfa-2b · Compensated liver disease · Age > 18 years · Written informed consent
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E.4 | Principal exclusion criteria |
· Treatment with any investigational drug within 30 days of entry to this protocol · Severe hepatitis activity as documented by ALT>10 x ULN · History of decompensated cirrhosis (defined as jaundice in the presence of cirrhosis, ascites, bleeding gastric or esophageal varices or encephalopathy) · Pre-existent neutropenia (neutrophils £1,800/mm3) or thrombocytopenia (platelets £90,000/mm3) · Co-infection with hepatitis C virus, hepatitis D virus or human immunodeficiency virus (HIV) · Other acquired or inherited causes of liver disease: alcoholic liver disease, obesity induced liver disease, drug related liver disease, auto-immune hepatitis, hemochromatosis, Wilson’s disease or alpha-1 antitrypsin deficiency · Alpha fetoprotein > 50 ng/ml · Hyper- or hypothyroidism (subjects requiring medication to maintain TSH levels in the normal range are eligible if all other inclusion/exclusion criteria are met) · Immune suppressive treatment within the previous 6 months · Contra-indications for alfa-interferon therapy like suspected hypersensitivity to interferon or PEG-interferon or any known pre-existing medical condition that could interfere with the patient's participation in and completion of the study. · Pregnancy, breast-feeding · Other significant medical illness that might interfere with this study: significant pulmonary dysfunction in the previous 6 months, malignancy other than skin basocellular carcinoma in previous 5 years, immunodeficiency syndromes (e.g. HIV positivity, auto-immune diseases, organ transplants other than cornea and hair transplant) · Any medical condition requiring, or likely to require chronic systemic administration of steroids, during the course of the study · Substance abuse, such as alcohol (³80 g/day), I.V. drugs and inhaled drugs in the past 2 years. · Any other condition which in the opinion of the investigator would make the patient unsuitable for enrollment, or could interfere with the patient participating in and completing the study
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary outcome (response): Sustained response defined as HBV DNA level < 200 IU/ml and HBeAg loss at week 72 Secondary outcomes: · Frequency, phenotype and function of NK cells,Treg and DCs. · Determination of HBV-specific T cell response · Determination of HBV and proteins in/on NK cells
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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 | No |
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 | 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 | 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.8.3 |
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 | 2 |
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 | Information not present in EudraCT |
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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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 | 3 |
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 | 3 |
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 |