Hepatitis B Vaccine for Non-responders
Condition: Hepatitis B
MeSH terms: Hepatitis A; Hepatitis B; Hepatitis
Study type: Interventional
Phase: Phase 2

Summary: 
      In the current study, the investigators study the efficacy of the HBAI20 vaccine to induce
      seroprotection in registered non-responders (adults who were previously vaccinated with the
      HBVaxPro-10μg but did not achieve seroprotection). The study will further assess the safety
      of the HBAI20 vaccine in comparison with HBVaxPro-10μg.
    

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 (IL-2) molecules attached to alum), facilitating the slow release of highly
      concentrated IL-2 nano aggregates. In preclinical experiments, vaccination of mice, rats, and
      rabbits with the new HBAI20 vaccine results in higher and earlier immune responses to HBsAg
      compared to vaccination with one of the standard Hepatitis B vaccines. The phase 1 clinical
      trial showed that the HBAI20 vaccine was well tolerated and it induced protective anti
      Hepatitis B antibody titers in 9 out of 10 non-responders (subjects vaccinated at least 6
      times with the Hepatitis B vaccine). The phase 2 clinical trial will be conducted in order to
      assess the immunogenicity and safety of the AI20 adjuvant and further test if the AI20
      adjuvanted Hepatitis B vaccine induces protective antibody titers in the vaccinated
      non-responders.

      Objective: In the current study, the investigators study the efficacy of the HBAI20 vaccine
      to induce seroprotection. Furthermore, the investigators will compare the safety of the
      HBAI20 vaccine with the HBVaxPro-10μg.

      Study design:

      Multicenter double blinded randomized controlled intervention phase II study.

      Study population:

      Registered non-responders after at least 3 HBV vaccinations (n=132- 140) 18-59 years of age,
      males and females.

      Intervention:

      The study will include 2 groups. HB vaccine registered non-responder subjects after at least
      3 vaccinations are randomized into group 1 (n= 33 to 35) or 2 (n= 99 to 105) at a 1 to 3
      ratio. No less than 40% of the subjects of each group should have received only 1 series of
      Hepatitis B vaccination. "Group 1" subjects receive the standard HB vaccine (HBVaxPro-10μg)
      and "Group 2" subjects receive the HBAI20 vaccine. All study subjects will receive 3
      vaccinations separated by one month (0, 1, and 2 months) in accordance with the recommended
      vaccination schedule for non-responders in the Netherlands.

      Main study parameters/endpoints:

      The primary study parameter is the immunogenicity of the adjuvanted vaccine. The
      immunogenicity of the adjuvanted vaccine is measured as the percentage of subjects that
      attain seroprotection after the first vaccination at 1, 2, and 3,5 months (HBsAg antibodies
      ≥10 mIU/ml measure by the COBAS system). The secondary study parameter is the safety of the
      vaccination. The safety of the vaccination is the number and severity of the local and
      systemic adverse reactions.

      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 2 months from the beginning of the
      study and invited to the hospital or vaccination centre for 4 or 5 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.
      Subjects may benefit from this study by becoming immunized (seroprotected) against Hepatitis
      B. Becoming seroprotected is important for the non-responder subjects because most of the
      registered non-responders are healthcare workers who can be exposed to the Hepatitis B virus.
    

Intervention name(s): HBVaxPro; HBAI20
Intervention type(s): Biological; Biological
Intervention description(s): Three doses of HBVaxPro-10μg at 0, 1, and 2 months. The HBVaxPro-10μg vaccines are administered strictly intramuscularly in the deltoid muscle and must not be injected intravascularly.; Three doses of HBAI20 at 0, 1, and 2 months. The HBAI20 vaccines are administered strictly intramuscularly in the deltoid muscle and must not be injected intravascularly.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Interleukin-2; Hepatitis B Vaccines; Non-responders; Liver Diseases; Digestive system; Vaccines