Clinical trial NCT01374308: NASVAC Phase-III Trial in Chronic Hepatitis B (CHB) Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Chronic Hepatitis B
Keywords: NASVAC
Pegylated Interferon-2b
CHB
Lead sponsor: Clinical Research Organization, Dhaka, Bangladesh
Sponsor class: OTHER
First posted: 2011-06-15
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).

Detailed description: 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.

Primary outcomes:
measure: Number of study participants with virological and or biochemical response as a measure of efficacy
timeFrame: At week 96
Secondary outcomes:
Other outcomes:
Locations:
city: Dhaka
country: Bangladesh
facility: Farabi General Hospital
Study officials:
affiliation: Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
name: Mamun A Mahtab, MSc MD FACG
role: PRINCIPAL_INVESTIGATOR
References:
citation: Al Mahtab M, Akbar SMF, Aguilar JC, Guillen G, Penton E, Tuero A, Yoshida O, Hiasa Y, Onji M. Treatment of chronic hepatitis B naive patients with a therapeutic vaccine containing HBs and HBc antigens (a randomized, open and treatment controlled phase III clinical trial). PLoS One. 2018 Aug 22;13(8):e0201236. doi: 10.1371/journal.pone.0201236. eCollection 2018.