In a minority of the population (5-10%) standard vaccines against Hepatitis-B do not induce protective immunity, even after prolonged and repeated vaccination courses. Non- responsiveness to hepatitis-B vaccination poses a severe problem for people with high risk of infection (e.g. medical and laboratory staff, surgeons). Several approaches have been proposed to overcome non- responsiveness, however these work only to a minimal extent leaving too many people unprotected.
Conditions
Interventions
Trade Name: HBVAXPRO 10 micrograms, suspension for injection in pre-filled syringe Hepatitis B vaccine (rDNA)
Product Name: HBVaxPRO 10 micrograms
Pharmaceutical Form: Solution for injection
INN or Pr
Sponsors
CyTuVax BV
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: In good health as determined by the outcome of medical history, physical examination screening/baseline labs and clinical judgment of the clinical investigator Age 18 to 59 years, inclusive at the time of enrollment Willing and able to adhere to the study regimen Having a signed informed consent form Documented non-responders: Subjects with documented one or more cycles of Hepatitis B vaccination (total of 3 or more vaccinations) and titer analysis that show that they have not developed the Hepatitis B antibody titer recommended after standard vaccination: anti-HBsAg antibody titer superior to 10mIU/ml Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 140 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Any infectious disease at the time of screening and/or enrollment Positive HIV, Hepatitis B virus or Hepatitis C virus serology Known or suspected immune deficiency Known or suspected disease that influences the immune system including chronic allergies that require frequent anti-allergy medication, cancer and transplantation recipients Known or suspected allergy to any of the vaccine components: see IB, IMPD Dialysis patient History of unusual or severe reactions to any previous vaccination History of any neurologic disorder, including epilepsy and autism Use of medication that influences the immune system (immune suppressive treatment or daily use of corticosteroids) Any vaccination within 3 months before screening Blood donation within 1 month before screening Administration of plasma (incl. immunoglobulins) or blood products within 12 months before screening Participation in another clinical trial within 3 months before screening Abnormal pre-treatment laboratory parameters which are clinically relevant according to the investigator Bleeding disorders, or use of medication for bleeding disorders, and use of anti-coagulants Female subjects planning to become pregnant or breastfeeding babies until visit 4 Females: positive urine pregnancy test at screening date Excessive alcohol or controlled drug use - More than 2 alcohol measures per day (one alcohol measure is a beer (250ml) or one glass of wine (125ml) or one strong measure (35ml) or one port/sherry (75ml)). Regular use of controlled drugs Any Hepatitis B vaccination in the last 6 months
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary study parameter is the determination the immunogenicity of the HBAI vaccine and how it compares with the standard HBVaxPro-10µg. The immunogenicity will be measured as the antibody titer specific for Hepatitis B which will be collected by the COBAS® system (Roche). The immunogenicity of the different vaccines will be assessed primarily as the percentage of individuals that become seroprotected with an anti HBsAg antibody titer equal or higher than 10mIU/ml. Other measurements of immunogenicity will the the Geometric Mean Titre and frozen PBMC will be used to investigate cellular immunogenicity of the different vaccines. In particular: epitope specificity, differentiation, maturation, and functionality of CD4+ T cells specific for HBsAg.;Secondary Objective: The secondary objective is to evaluate the safety and tolerability of the CyTuVax Hepatitis B vaccine in non-responders: assessment of the local and systemic adverse reactions. The time frame for the determination of the vaccine safety is within the first 30 days after first, second, and 45 days after the third vaccination. The whole duration of the study protocol, which include the 3 vaccinations with the IMP and the 6 weeks after, are consider the safety assessment period. Adverse effects will be recorded as described on section 8.1.1 of the present document. ;Primary end point(s): The primary study endpoint is the immunogenicity of the adjuvanted vaccine. The immunogenicity of the vaccine is assessed as the percentage of subjects that have an anti HBsAg antibody titer higher or equal to 10mIU/ml 6 weeks after the 3rd vaccination. The antibody titers specific for Hepatitis B will be measured using an immunochemistry COBAS assay. ;Timepoint(s) of evaluation of this end point: 102 days after the beginning of the study. 42 days after the last vaccination | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints for safety are the number and intensity of local and systemic adverse reactions and the determination of the dose. To determine the safety of the adjuvanted vaccine, subjects will be observed during the first 30 minutes after vaccination in order to record the occurrence of acute reactions. A diary will be given to each subject for reporting of adverse events on the day of vaccination and during the next 4 days after the day of vaccination for a total of 5 days. ;Timepoint(s) of evaluation of this end point: 102 days after the beginning of the study. 42 days after the last vaccination | — |
Countries
Belgium, Netherlands
Contacts
Public ContactDepartment of Medical Microbiology
Maastricht University Medical Center
Outcome results
None listed