rTSST-1 Variant Vaccine Phase 1 First-in-man Trail

The BioMed rTSST-1 Variant Vaccine has been developed by Biomedizinische ForschungsgmbH as one component of a polyvalent staphylococcal vaccine for the prevention of toxic shock and hyperimmunization of donors for the production of TSST-1 immunoglobulin.

This is a prospective, partly randomized, parallel control, dose escalation study of the safety and immunogenicity of the BioMed rTSST1 Variant Vaccine compared to adjuvant in healthy adults.

28 - 3 days prior to entry into the study, 50 male and female subjects 18 - 64 years in age will be screened for eligibility , screening criteria to include physical examination, medical history, pregnancy/ adequate contraception in females, HIV Ab, hepatitis C virus antibodies (HCV Ab), hepatitis B antigen (HBs Ag) and TSST-1 Ab. 46 of these subjects will be entered into the study.

In a first step, two subjects will receive the adjuvanted Vaccine containing 100 ng rTSST-1 Ag and one subject will receive the adjuvant containing 0.2 mg Al(0H)3 only (Group 1). The subjects will be seen four times after immunization in a period of 14 days (6 h, 48 h + 2 hrs, 7 + 1 days and 14 + 2 days).Tests and examinations will include vital signs, hematology and clinical chemistry parameters, C-reactive protein, cytokines, TSST-Ab , local reactions and adverse events.

In the absence of clinically relevant adverse events , another three subjects will be entered into the study one week later, two of them to receive the adjuvanted Vaccine containing 300 ng rTSST-1 Ag, one receiving the adjuvant containing 0.6 mg Al(0H)3 (Group 2) and be followed for a period of 14 days as described above.

In the absence of clinically relevant adverse events , four more subjects will be entered into the study one week thereafter, three of them to receive the adjuvanted Vaccine containing 1 µg rTSST-1 Ag , one to receive adjuvant containing 1 mg Al(0H)3 alone (Group 3), and be followed for a period of 14 days in the manner described above.

Immunization will be repeated at the same dose level in each group one to two months after the first. Follow-up will be the same.

If immunogenicity can be shown after the second administration of the Vaccine containing 1 µg of rTSST-1 Ag, doses and sample sizes will be increased to Vaccine containing 3 µg , 10 µg, and 30 µg and adjuvant containing 1 mg Al(0H)3 in nine and three subjects in Groups 4 - 6, respectively. Otherwise, the sample size of 3 + 1 will continue until immunogenicity is seen at a higher dose level.

Subjects in Groups 4 - 6 will receive a second immunization at the respective dose level one to two months after the first, follow-up being the same as in Groups 1 - 3.

If there is no immune response in any dose group after the second immunization, a third injection will be given 4 - 8 weeks thereafter in dose groups of 1 µg (Groups 3 - 6) and above.

Immunogenicity is defined by seroconversion from a TSST-1 Ab titer of < 20 to > 40 or a 4-fold increase in TSST-1 Ab titer.

Subjects to receive vaccine containing 3 µg rTSST-1 Ag or more will be randomized.