nasvac phase-iii trial in chronic hepatitis b (chb) patients

Conditions: Chronic Hepatitis B

Summary: the general objective of the present clinical trial is to compare the therapeutic efficacy of a combination therapeutic vaccine containing hepatitis b surface antigen (hbsag) and hepatitis b core antigen (hbcag) \[later called nasvac\] with a commonly used antiviral drug, pegylated interferon in patients with chronic hepatitis b (chb).

to collect and assess data on the therapeutic potential of the nasvac in chb patients regarding: reduction of the serum hbv dna levels. reduction in the levels of alanine aminotransferase (alt) clearance of hepatitis b e antigen (hbeag) negativation or lowering of hbsag anti-hbsag/anti-hbeag seroconversion an additional objective of this study is to reconfirm the safety of nasvac in chb patients that has previously been shown by us in phase i-ii clinical trial in chb patients.

Eligibility criteria:
inclusion criteria: * hbsag+ serology for more than 6 months before the beginning of the treatment. in the last six months, according to hbeag serostatus, for: * hbeag (-) patients, with a) baseline hbv dna ≥ 103 and b) raised serum alt (x \>1 uln) or significant hepatic necroinflammation and/or fibrosis (hai-ni\>4 and/or hai-f \>2) or liver stiffness \>7.2 kpa. * hbeag (+) patients, with a) baseline hbv dna ≥ 104 and b) and raised serum alt (x \>1.5 uln) or significant hepatic necroinflammation and or fibrosis (hai-ni\>4 and/or hai-f \>2) or liver stiffness \>7.2 kpa. * patients of both sex from 18 to 60 years-old * no specific hepatitis b treatment at least for 6 months previous to the inclusion * voluntary signed informed consent to participate in the trial exclusion criteria: * condition of hbv asymptomatic carrier or cirrhosis or patients with primary hepatocellular carcinoma * positive serological markers for hepatitis c * positive serological markers for hiv * previous specific anti-hepatitis b treatment in the last 6 months. * critically ill patient history of heart or renal failure, hypertension, hyperthyroidism, epilepsy, immunodeficiency diseases, malignancies or any non-controlled systemic disease. * pregnancy or nursing women. women in fertile age without any contraceptive methods. * known severe allergic conditions (degree iii or iv asthma, urticaria, dermatitis, bronchitis, etc. or hypersensitivity to any of the ingredients present in the preparation). * severe psychiatric dysfunction or another limitation that prevents the patient's consent. * history of autoimmune diseases (such as sle, rheumatoid arthritis, multiple sclerosis, non controlled diabetes mellitus type 1) * history of other hepatic diseases of different etiology (such as alcoholism, autoimmune hepatitis, drug induced hepatitis, wilson's diseases, hemochromatosis) * history of immune suppressive disorder or administration of immune suppressive-immune modulator drugs (including steroids) during or in the 6 months previous to the study. * very high transaminase levels at the beginning of treatment (alt over 500 u/l) suggesting a not stable disease with risk for patient's health or acute flares over 15 times the upper limit of normality.

Keywords: nasvac pegylated interferon-2b chb