Amendment of rTSST-1 Variant Vaccine Phase 1 Clinical Trial
Condition: Toxic-Shock Syndrome; Sepsis
MeSH terms: Shock, Septic; Shock
Study type: Interventional
Phase: Phase 1

Summary: 
      Toxic Shock Syndrome (TSS) a severe condition with high morbidity and mortality results from
      the hosts overwhelming inflammatory response and cytokine storm. Staphylococcal superantigen
      toxins are the main causative agents. Toxic shock syndrome toxin (TSST-1) being responsible
      for almost all of menstruation associated and more than 50% of all other cases. There is no
      specific therapy. The Phase I study BioMed0713 demonstrated the safety and tolerability of
      the BioMed recombinant toxic shock syndrome toxin (rTSST-1) Variant Vaccine in healthy
      adults.

      The aim of this amendment is to demonstrate prolonged safety of the BioMed rTSST-1 Variant
      Vaccine and to assess persistence of antibodies generated in participants. The second aim of
      the study is to assess boosterability of the BioMed rTSST-1 Variant Vaccine.
    

Detailed description: 
      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, single-blinded follow-up study of the safety and immunogenicity of the
      BioMed rTSST1 Variant Vaccine compared to adjuvant in healthy adults.

      All subjects who received 2 doses of 100 ng or more of the rTSST-1 Variant Candidate Vaccine
      or placebo (Groups 1 - 6) will be followed up in a single-blinded manner for long-term
      immunogenicity 6 - 15 months after their last (= second) immunization to gain more data about
      persistence of TSST-1 Ab titer. As this part of the study occurs after unblinding of the
      study subjects, it is termed Part B (for better discrimination from double-blinded Part A).

      All participants will be invited for a blood withdrawal to determine TSST-1 antibodies.
      Independent of the TSST-1 Ab titer level, subjects will receive one booster immunization
      either according to their former allocated dose (group 4: 3µg or placebo, group 5: 10 µg or
      placebo, group 6: 30 µg or placebo) or 3µg or placebo (groups 1 - 3) in the same visit.

      Placebo will be administered according to the former allocated dose.

      The treated subjects will stay two hours after immunization at the department and will be
      followed up for 6 months.

      Rationale for reduced monitoring after immunization and follow up:

      The BioMed rTSST-1 Variant Vaccine demonstrated excellent local and systemic tolerability and
      safety and an absence of adverse events classified as clinically relevant during the conduct
      of the study. Therefore no abnormal findings are expected and the monitoring of the
      vaccinated subjects after immunization is reduced to two hours, there are three follow up
      visits planned, 24h (+-2 h), 28 days (+-7 days) and 6 months (+-28 days) after booster
      vaccination.
    

Intervention name(s): rTSST-1 Variant Candidate Vaccine
Intervention type(s): Biological
Intervention description(s): Immunization either according to their former allocated dose (group 4: 3 µg of candidate vaccine or placebo, group 5: 10 µg of candidate vaccine or placebo, group 6: 30 µg of candidate vaccine or placebo) or 3 µg of candidate vaccine or placebo (groups 1 - 3) from Phase I.
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Treatment