Clinical Trial of the BioMed rTSST-1 Variant Vaccine in Healthy Adults
Condition: Toxic Shock Syndrome
MeSH terms: Shock, Septic; Shock
Study type: Interventional
Phase: Phase 2

Summary: 
      Toxic Shock Syndrome (TSS) is a severe condition with high morbidity and mortality 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 extend the safety and tolerability of two doses of the BioMed
      recombinant toxic shock syndrome toxin (rTSST-1) Variant Vaccine after one to three
      vaccinations in healthy adults. The second aim of the study is to measure immunogenicity and
      persistence of antibodies which produced in response to treatment with the BioMed rTSST-1
      Variant Vaccine over a period of 12 months. These antibodies are expected to be important in
      prevention and mitigation of the diseases. 140 healthy adults, male and female, age 18-64
      years will be assigned to 7 groups comprising two doses of the vaccine or adjuvant at the
      Department of Clinical Pharmacology of the Medical University of Vienna. The patients will be
      monitored for vital signs, hematology, clinical chemistry, and antibodies against TSST-1.
      Immunization will be repeated 3 months after the first with the same dose and 6 months after
      the second immunization in the respective groups.

      Antibodies will be determined through monitoring TSST-1 binding antibodies as assessed
      through ELISA and neutralizing antibodies (exploratory endpoint) as assessed by inhibition of
      T cell activation (3H Thymidine incorporation; ≥ 50%).
    

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, randomized, parallel control, phase 2 study of extended safety, local
      tolerance, immunogenicity, and TSST-1 antibody persistence in healthy adults, who have been
      vaccinated with one, two or three doses of the BioMed rTSST1 Variant Vaccine compared to
      adjuvant.

      Over a period of 60 days prior to entry into the study, 145 male and female subjects 18 - 64
      years in age will be screened for eligibility. Screening criteria will 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. 140 qualified
      subjects will be entered into the study.

      Group 1 will receive 10 µg of rTSST-1 Variant Vaccine and two administrations of Adjuvant;
      Group 2 will receive the same dose of Vaccine twice and one dose of Adjuvant; and Group 3
      will be injected the 10 µg of the Vaccine three times. Groups 4 to 6 will be given 100 µg of
      Vaccine following the same schedule. Group 7 will receive Al(OH3) adjuvant three times.

      Prior to, and 24 h (+3 h) after each vaccination, the subjects will be examined for vital
      signs. Blood will be drawn for hematology, clinical chemistry tests, and C-reactive protein.
      Local reactions and adverse events will be assessed in all post vaccination visits.

      The subjects will be followed up for a period of 3 months (± 2 weeks) or optionally 18 months
      (± 12 weeks) if they decide to take part in the long-term follow-up, during which they will
      return to the clinic every three months (± 2 weeks). Tests performed will include vital
      signs, local reactions, clinical chemistry, C-reactive protein. Adverse events will be
      recorded.

      Binding and neutralizing TSST-1 antibodies will be determined prior to each vaccination and
      every three months during the treatment and follow-up periods.

      Each participant will be in the study for 12 to 14, or optionally 24 months, if they decide
      to take part in the long-term follow-up.

      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. Neutralization will be defined as a three-fold increase
      of neutralization titer.
    

Intervention name(s): rTSST-1v
Intervention type(s): Biological
Intervention description(s): Each subject of a total of seven groups will receive three injections (first injection day 0; second injection 3 months ± 4 weeks after the first, third injection 6 months ± 4 weeks after the second) of one of two different doses of Vaccine or Adjuvant, each group comprising 20 subjects. Subjects will be controlled 24 h post vaccination. Follow-up will last 18 months on the average, with visits every three months (± 2 weeks). Response to treatment is defined by seroconversion from a TSST-1 binding Ab titer of < 20 to > 40 or a 4-fold increase in TSST-1 binding Ab titer .
Allocation: Randomized
Intervention model: Sequential Assignment
Intervention model description: Two different doses of rTSST-1 Variant Vaccine were tested in different administrational schedules. These were: a comparison of 10µg versus 100µg rTSST-1 Variant Vaccine administered one, two, or three times.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Sepsis; Vaccination