rTSST-1 Variant Vaccine Phase 1 First-in-man Trail
Condition: Toxic Shock Syndrome; Vaccination; 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 aim of this study is to demonstrate the safety and tolerability of the BioMed recombinant
      toxic shock syndrome toxin (rTSST-1) Variant Vaccine in healthy adults. The second aim of the
      study is to measure antibodies in the blood of these healthy volunteers which have been
      produced in response to treatment with the BioMed rTSST-1 Variant Vaccine. These antibodies
      are expected to be important in resistance against the diseases. 46 healthy adults, male and
      female, age 18-64 years will be assigned to 6 dose groups of the vaccine at the Department of
      Clinical Pharmacology of the Medical University of Vienna. The patients will be monitored for
      vital signs, hematology, clinical chemistry, blood cytokine level and antibodies against
      TSST-1. Immunization will be repeated 4 weeks after the first with the same dose.
    

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, 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.
    

Intervention name(s): rTSST-1 Variant Candidate Vaccine
Intervention type(s): Biological
Intervention description(s): In the absence of adverse events classified as clinically relevant, interval between dose escalations 1 week. Immunization to be repeated at the same dose level 1 - 2 months later. If immunogenicity can be shown after the second administration of 1 µg, the sample size will be increased from 3 + 1 to 9 + 3. Otherwise, the sample size of 3 + 1 will continue until immunogenicity is seen at a higher dose level. 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 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 .
Patients 3 µg or more will be randomized.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment