NASVAC Phase-III Trial in Chronic Hepatitis B (CHB) Patients

Phase IIII Study of a Therapeutic Vaccine Candidate Containing Hepatitis B Virus (HBV) Core Antigen (HBcAg) and HBV Surface Antigen (HBsAg) for Treatment of Patients With Chronic HBV Infection

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.

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.