Clinical Trial of the BioMed rTSST-1 Variant Vaccine in Healthy Adults

Phase 2

Completed

Conditions: Toxic Shock Syndrome

Interventions: Biological: rTSST-1v

Registration Number: NCT02814708

Lead Sponsor: Biomedizinische Forschungs gmbH

Brief 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 140

Inclusion Criteria

males or females aged 18-64 years
signed informed consent
physical exam: no abnormal findings unless considered irrelevant by the investigator
uneventful medical history
Females with childbearing potential: adequate contraception

Exclusion Criteria

females with childbearing potential: pregnancy, lactation or unreliable contraception
positive HIV Ab and/or positive HCV Ab and/or positive HBsAG signs and symptoms of autoimmunity
TSST-1 Ab titer > 1:1000
current or recent (< 1 month) immunosuppressive therapy with corticosteroids or immunomodulators

Study & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Dose Group 5	rTSST-1v	rTSST-1 Variant Candidate Vaccine 100µg Number of Immunizations: 2
Dose Group 2	rTSST-1v	rTSST-1 Variant Candidate Vaccine 10µg Number of Immunizations: 2
Dose Group 3	rTSST-1v	rTSST-1 Variant Candidate Vaccine 10µg Number of Immunizations: 3
Dose Group 6	rTSST-1v	rTSST-1 Variant Candidate Vaccine 100 µg Number of Immunizations: 3
Dose Group 1	rTSST-1v	rTSST-1 Variant Candidate Vaccine 10µg Number of Immunizations: 1
Dose Group 4	rTSST-1v	rTSST-1 Variant Candidate Vaccine 100µg Number of Immunizations: 1
Dose Group 7	rTSST-1v	Al(OH)3 Adjuvant, 1mg Number of Immunizations: 3

Primary Outcome Measures

Name	Time	Method
Number of Participants (Percentage) With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment	12 months and 18 months follow up

Secondary Outcome Measures

Name	Time	Method
Number of Participants With a Fold Increase of ELISA IgG Against rTSST-1	12 months and 18 months follow up	Fold increase of antibody titer against rTSST-1 ELISA from prevaccination titer. 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. Comparison with placebo comparator recipients.