Safety and Immunogenicity of HBAI20 Hepatitis B Vaccine in Naive Adults and Non-responders
Condition: Hepatitis B
MeSH terms: Hepatitis A; Hepatitis B; Hepatitis
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to determine whether the HBAI20 vaccine is safe and more
      immunogenic than the HBVaxPro-10µg in people who have never been vaccinated with a hepatitis
      B vaccine and in people who have been vaccinated 6 times with hepatitis B vaccine but do not
      have a protective anti hepatitis B antibody titer.
    

Detailed description: 
      Rationale: Worldwide, people are suffering from the consequences of Hepatitis B (HB) virus
      infection. Currently available vaccines are protective in most of the vaccinees, however, a
      small part of the population does not respond to these vaccines (non-responders). A new
      adjuvant (AI20) has been developed by CyTuVax to improve the standard Hepatitis B vaccine for
      the protection of non-responders. The AI20 adjuvant consists of depot-attached rhuIL-2
      (aggregated Interleukin-2 molecules attached to alum), facilitating the slow release of
      highly concentrated IL-2 nano aggregates. As shown in preclinical experiments, vaccination of
      mice, rats, and rabbits with the new HBAI20 vaccine results in higher and earlier immune
      responses to Hepatitis B surface antigen (HBsAg) compared to vaccination with one of the
      standard Hepatitis B vaccines. This clinical study will be done in order to assess the safety
      of the AI20 adjuvant and test if the AI20 adjuvanted Hepatitis B vaccine induces protective
      antibody titers in the vaccinated non-responders.

      Objective: In the current study we investigate the safety of the HBAI20 vaccine. Furthermore,
      the efficacy of the HBAI20 vaccine in non-responders is investigated.

      Study design: Partly double blinded randomized controlled intervention phase I study, partly
      open-label phase I study.

      Study population: Healthy volunteers (n=24) and registered non-responders (n=12), 18-59 years
      old, males and females.

      Intervention: The study will include 3 groups. HB vaccine naïve healthy subjects are
      randomized into group 1 and 2 and registered non-responders are included in group 3.

      "Group 1" subjects receive the standard HB vaccine (HBVaxPro-10µg), "Group 2" and "Group 3"
      subjects receive the HBAI20 vaccine. 2 subjects from "Group 3" will constitute "Group 3
      pilot" and will start the study 7 days before the start of the remaining "Group 3" subjects.

      All study subjects in groups 2 and 3 will receive two vaccinations with the assigned
      investigational medical product (IMP) at 0 and 1 month and one regular booster vaccination
      with the standard HB vaccine HBVaxPro-10µg 6 months after the first dose according to the
      recommended vaccination schedule for HBVaxPro-10µg.

      Main study parameters/endpoints: The primary study parameter is the number and intensity of
      local and systemic adverse reactions (redness, swelling, impaired movement). The secondary
      study parameter is the HBAI20 vaccine immunogenicity as calculated by the median titer,
      geometric mean titer, geometric mean titer increase, proportion of subjects with a virus
      specific antibody titer measure by the COBAS system of ≥ 10 mIU/ml, and seroconversion rate.
      Seroconversion is defined as a four-fold increase in titer or a conversion from seronegative
      to an anti-HBsAg antibody titer of more than 10 mIU/ml after vaccinations.

      Nature and extent of the burden and risks associated with participation, benefit and group
      relatedness: Study subjects will be vaccinated 3 times at 0, 1 and 6 months from the
      beginning of the study and invited to the hospital for 8 visits. The risks associated with
      participation in this study are considered to be low and comparable with standard vaccines.
      Physical discomfort after vaccine administration can occur at the injection site (redness,
      swelling, etc.) and systemically (fever, fatigue, headache). Effects are expected to occur
      for a short period of time (within the first 4 days after the first and second injection). In
      addition subjects may experience adverse reactions to the cytokine component of the adjuvant.
      Because of the very low dose of the cytokine component of the adjuvant, which will be
      gradually released, the risks are expected to be low. The potential risks of venepuncture for
      blood sampling are mild pain and haematoma, and are considered low.

      The naïve subjects participating in this study will benefit from participating by receiving
      immunization against Hepatitis B. Subjects in the non-responder group may benefit when they
      become responders due to the effect of the HBAI20 vaccine.
    

Intervention name(s): HBVaxPro; HBAI20
Intervention type(s): Biological; Biological
Intervention description(s): 3 vaccinations with HBVaxPro-10ug at 0, 30, and 180 days.; 2 vaccinations with HBAI20 at 0 and 30 days and 1 vaccination with HBVaxPro-10ug at 180 days.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Adjuvants, immunologic; Interleukin-2; Hepatitis B vaccines; Non-responders