Toxic Shock Syndrome Clinical Trial
Official title:
Phase 1 Clinical Trial of the BioMed rTSST-1 Variant Vaccine in Healthy Adults
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.
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.
;
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT02814708 -
Clinical Trial of the BioMed rTSST-1 Variant Vaccine in Healthy Adults
|
Phase 2 | |
| Completed |
NCT02219165 -
Efficacy of IntraVenous ImmunoGlobulins in Toxic Shock Syndromes: a Paediatric Pilot Study
|
Phase 2 |