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

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.

• Biological: NASVAC
  NASVAC will be administered every 2 weekly intra-nasally at a dose of 100 micro grams for 5 times followed by every 2 weekly administration of 100 micro grams intra-nasally plus 100 micro grams subcutaneously.
• Drug: Pegylated interferon alpha 2b
  Injection Pegylated interferon alpha 2b will be administered once weekly subcutaneously at a dose of 180 micro grams for 48 weeks
  Other Names:

  • Pegasys
  • Pegintron
  • Pegin
  • Optipeg
  • Peghebron

• Experimental: NASVAC
  NASVAC will be administered every 2 weekly intra-nasally at a dose of 100 micro grams for 5 times followed by every 2 weekly administration of 100 micro grams intra-nasally plus 100 micro grams subcutaneously.
  Intervention: Biological: NASVAC
• Active Comparator: Pegylated interferon alpha 2b
  Injection Pegylated interferon alpha 2b will be administered once weekly subcutaneously at a dose of 180 micro grams for 48 weeks
  Intervention: Drug: Pegylated interferon alpha 2b

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.