A Study to Qualify an In-house Reference Standard Batch of Sci-B-Vac™
Condition: Hepatitis B
MeSH terms: Hepatitis B
Study type: Interventional
Phase: Phase 4

Summary: 
      Each Sci-B-Vac™ lot to be released to the market is tested in comparison to a reference
      batch,which has to be tested in a human clinical trial. This study was conducted by SciVac
      Ltd. to to evaluate the immunogenicity and explore the immune kinetics of Sci-B-Vac™ in
      support of its qualification as new reference standard which according to the European
      Pharmacopeia (Ph.Eur. 1056) should elicit ≥ 95% seroprotection rate (SPR) of Hepatitis B
      surface (HBs) antibody concentrations ≥ 10 milli-International Units (mIU) per ml in young,
      healthy adult subjects.
    

Detailed description: 
      This study was a post-marketing, open-label, single arm study in healthy volunteers who had
      never been vaccinated with any hepatitis B vaccine and were seronegative to HBsAg, Hepatitis
      B core (HBc) and HBs antibodies. This study consisted of three periods: screening period (up
      to 1 month prior to first vaccination), treatment (Day 1 to month 6), and post-vaccination
      follow-up period (months 6 -12). Immunogenicity endpoints were examined one month after the
      first injection and at every month until month 6, then at months 7, 9 and 12. The primary
      safety endpoint was the frequency, severity, and duration of adverse events, including
      clinically-significant laboratory abnormalities after administration of Sci-B-Vac™.

      Statistical Methods: A total of 92 subjects were recruited into the study. Subjects who fully
      complied with the study protocol, had no inclusion/exclusion criteria violation and who early
      terminated the study but reached the primary endpoint prior to withdrawal (modified
      intention-to-treat (mITT) population) were included in the final population for statistical
      analysis. mITT population was defined as the subset of the ITT set, which consisted of all
      enrolled subjects who were vaccinated at least once with Sci-B-Vac™ and had at least one
      post-vaccination follow-up visit, fully complied with the protocol and had no violation of
      the inclusion/exclusion criteria. Eligible subjects were followed for a total duration of 12
      months.

      Significance Level: The overall significance level for this study was 5% using two-tailed
      tests. Sample size determination was performed under the following assumptions:

      The primary endpoint for the study was the SPR, defined as the proportion of subjects with
      HBs antibody titer ≥10 mIU/ml by month 7 (i.e. one month after the third immunization with
      Sci-B-Vac™). Subjects terminated early from the study for any reason at any time and who met
      the primary endpoint were included.

      In compliance with the European Pharmacopeia, the SPR threshold was set at ≥ 95%. Based on a
      9% margin of non-inferiority, the study was considered successful if the lower bound of the
      95.0% exact confidence interval (CI) was 86.0% or more (lower non-inferiority limit) by month
      7.

      The secondary objective of the study was to explore kinetics of immune response induced by
      Sci-B-Vac™ based on serial immunogenicity measurements.

      Demographic and baseline data as well as disease prognostic factors, medical history and
      prior medications were summarized for the mITT population,For continuous variables,
      descriptive statistics (number [n], mean, standard deviation (SD), standard error, median,
      minimum, and maximum) were provided. For categorical variables, subject counts and
      percentages were provided.
    

Intervention name(s): Sci-B-Vac™
Intervention type(s): Biological
Intervention description(s): Sci-B-Vac™ is a recombinant Hepatitis B vaccine, produced by SciVac Israel Ltd under good manufacturing practices (GMP). It contains the 3 surface antigens of the Hepatitis B virus: HBs, pre-S1 and pre-S2. Each 1 ml dose contains sterile 10 μg Hepatitis B virus surface antigens. It is formulated for intramuscular injection supplied in single use vials containing 1ml suspension.
Intervention model: Single Group Assignment
Intervention model description: This study was an open-label, single arm study. No control groups were deemed necessary since this was a phase IV trial for which the goal, set according to the European Pharmacopeia 1056, was to achieve 95% SPR after the third vaccination.
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: SciB018; Prophylactic vaccine; Sci-B-Vac™; HepB vaccines; Phase 4; pre-S1; pre-S2; Surface antigen