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

• Sponsor: Biomedizinische Forschungs gmbH (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02814708
• Collaborator: Medical University of Vienna (Other)
• Enrollment: 140
• Location: 1
• Arms: 7
• Duration (Months): 56
• Patients Per Site Per Month: 2.5

Study Details

Study Description

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%).

Condition or Disease	Intervention/Treatment	Phase
Toxic Shock Syndrome	Biological: rTSST-1v	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 140 participants
• 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.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
• Official Title: Phase 2 Clinical Trial of the BioMed rTSST-1 Variant Vaccine in Healthy Adults
• Study Start Date: May 1, 2016
• Actual Primary Completion Date: May 1, 2020
• Actual Study Completion Date: Jan 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dose Group 1 rTSST-1 Variant Candidate Vaccine 10µg Number of Immunizations: 1	Biological: rTSST-1v; 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 .
Experimental: Dose Group 2 rTSST-1 Variant Candidate Vaccine 10µg Number of Immunizations: 2	Biological: rTSST-1v; 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 .
Experimental: Dose Group 3 rTSST-1 Variant Candidate Vaccine 10µg Number of Immunizations: 3	Biological: rTSST-1v; 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 .
Experimental: Dose Group 4 rTSST-1 Variant Candidate Vaccine 100µg Number of Immunizations: 1	Biological: rTSST-1v; 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 .
Experimental: Dose Group 5 rTSST-1 Variant Candidate Vaccine 100µg Number of Immunizations: 2	Biological: rTSST-1v; 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 .
Experimental: Dose Group 6 rTSST-1 Variant Candidate Vaccine 100 µg Number of Immunizations: 3	Biological: rTSST-1v; 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 .
Placebo Comparator: Dose Group 7 Al(OH)3 Adjuvant, 1mg Number of Immunizations: 3	Biological: rTSST-1v; 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 .

Outcome Measures

Primary Outcome Measures

1. 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

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 64 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Medical University of Vienna Department of Clinical Pharmacology	Vienna		Austria	1090

Sponsors and Collaborators

• Biomedizinische Forschungs gmbH
• Medical University of Vienna

Investigators

• Study Director: Martha M Eibl, MD, Biomedizinische Forschungsgmbh
• Principal Investigator: Bernd Jilma, MD, Medical University of Vienna

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 20, 2020

More Information

Publications

None provided.

• Responsible Party: Biomedizinische Forschungs gmbH
• ClinicalTrials.gov Identifier: NCT02814708
• Other Study ID Numbers: BioMed 0515
• First Posted: Jun 28, 2016
• Last Update Posted: Jan 4, 2022
• Last Verified: Dec 1, 2021

• Keywords provided by Biomedizinische Forschungs gmbH: Sepsis; Vaccination
• Additional relevant MeSH terms: Shock, Septic; Shock

Study Results

Participant Flow

Arm/Group Title	Dose Group 1	Dose Group 2	Dose Group 3	Dose Group 4	Dose Group 5	Dose Group 6	Dose Group 7
Arm/Group Description	rTSST-1 Variant Candidate Vaccine 10µg Number of Immunizations: 1 rTSST-1v: 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 .	rTSST-1 Variant Candidate Vaccine 10µg Number of Immunizations: 2 rTSST-1v: 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 .	rTSST-1 Variant Candidate Vaccine 10µg Number of Immunizations: 3 rTSST-1v: 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 .	rTSST-1 Variant Candidate Vaccine 100µg Number of Immunizations: 1 rTSST-1v: 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 .	rTSST-1 Variant Candidate Vaccine 100µg Number of Immunizations: 2 rTSST-1v: 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 .	rTSST-1 Variant Candidate Vaccine 100 µg Number of Immunizations: 3 rTSST-1v: 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 .	Al(OH)3 Adjuvant, 1mg Number of Immunizations: 3 rTSST-1v: 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 .
Period Title: Overall Study
STARTED	20	20	20	20	20	20	20
COMPLETED	18	17	19	20	17	16	19
NOT COMPLETED	2	3	1	0	3	4	1

Baseline Characteristics

Arm/Group Title	Dose Group 1	Dose Group 2	Dose Group 3	Dose Group 4	Dose Group 5	Dose Group 6	Dose Group 7	Total
Arm/Group Description	rTSST-1 Variant Candidate Vaccine 10µg Number of Immunizations: 1 rTSST-1v: 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 .	rTSST-1 Variant Candidate Vaccine 10µg Number of Immunizations: 2 rTSST-1v: 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 .	rTSST-1 Variant Candidate Vaccine 10µg Number of Immunizations: 3 rTSST-1v: 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 .	rTSST-1 Variant Candidate Vaccine 100µg Number of Immunizations: 1 rTSST-1v: 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 .	rTSST-1 Variant Candidate Vaccine 100µg Number of Immunizations: 2 rTSST-1v: 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 .	rTSST-1 Variant Candidate Vaccine 100 µg Number of Immunizations: 3 rTSST-1v: 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 .	Al(OH)3 Adjuvant, 1mg Number of Immunizations: 3 rTSST-1v: 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 .	Total of all reporting groups
Overall Participants	20	20	20	20	20	20	20	140
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	20 100%	20 100%	20 100%	20 100%	20 100%	20 100%	20 100%	140 100%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	31.7 (11.3)	31.3 (11.9)	29.2 (9.8)	30.2 (8.5)	31.2 (12.1)	36.6 (11.8)	34.2 (12.5)	31.9 (11.2)
Sex: Female, Male (Count of Participants)
Female	6 30%	9 45%	8 40%	5 25%	10 50%	5 25%	6 30%	49 35%
Male	14 70%	11 55%	12 60%	15 75%	10 50%	15 75%	14 70%	91 65%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	1 5%	0 0%	0 0%	1 5%	0 0%	2 1.4%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
White	20 100%	20 100%	19 95%	20 100%	20 100%	19 95%	20 100%	138 98.6%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Austria	20 100%	20 100%	20 100%	20 100%	20 100%	20 100%	20 100%	140 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

any suspected related systemic AE

Arm/Group Title	Dose Group 1	Dose Group 2	Dose Group 3	Dose Group 4	Dose Group 5	Dose Group 6	Dose Group 7
Arm/Group Description	rTSST-1 Variant Candidate Vaccine 10µg Number of Immunizations: 1 rTSST-1v: 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 .	rTSST-1 Variant Candidate Vaccine 10µg Number of Immunizations: 2 rTSST-1v: 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 .	rTSST-1 Variant Candidate Vaccine 10µg Number of Immunizations: 3 rTSST-1v: 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 .	rTSST-1 Variant Candidate Vaccine 100µg Number of Immunizations: 1 rTSST-1v: 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 .	rTSST-1 Variant Candidate Vaccine 100µg Number of Immunizations: 2 rTSST-1v: 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 .	rTSST-1 Variant Candidate Vaccine 100 µg Number of Immunizations: 3 rTSST-1v: 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 .	Al(OH)3 Adjuvant, 1mg Number of Immunizations: 3 rTSST-1v: 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 .
Measure Participants	20	20	20	20	20	20	20
Count of Participants [Participants]	9 45%	11 55%	11 55%	12 60%	10 50%	13 65%	10 50%

2. Secondary Outcome

Title	Number of Participants With a Fold Increase of ELISA IgG Against rTSST-1
Description	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.
Time Frame	12 months and 18 months follow up

Outcome Measure Data

Analysis Population Description

per protocol population included in calculation analysed over time by treatment

Arm/Group Title	Dose Group 1	Dose Group 2	Dose Group 3	Dose Group 4	Dose Group 5	Dose Group 6	Dose Group 7
Arm/Group Description	rTSST-1 Variant Candidate Vaccine 10µg Number of Immunizations: 1 rTSST-1v: 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 .	rTSST-1 Variant Candidate Vaccine 10µg Number of Immunizations: 2 rTSST-1v: 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 .	rTSST-1 Variant Candidate Vaccine 10µg Number of Immunizations: 3 rTSST-1v: 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 .	rTSST-1 Variant Candidate Vaccine 100µg Number of Immunizations: 1 rTSST-1v: 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 .	rTSST-1 Variant Candidate Vaccine 100µg Number of Immunizations: 2 rTSST-1v: 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 .	rTSST-1 Variant Candidate Vaccine 100 µg Number of Immunizations: 3 rTSST-1v: 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 .	Al(OH)3 Adjuvant, 1mg Number of Immunizations: 3 rTSST-1v: 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 .
Measure Participants	18	17	19	20	17	16	19
12 months	13 65%	15 75%	17 85%	17 85%	13 65%	15 75%	0 0%
18 months	10 50%	12 60%	13 65%	14 70%	12 60%	12 60%	0 0%

Adverse Events

Time Frame	27 months
Arm/Group Title	Dose Group 1		Dose Group 2		Dose Group 3		Dose Group 4		Dose Group 5		Dose Group 6		Dose Group 7
Arm/Group Description	rTSST-1 Variant Candidate Vaccine 10µg Number of Immunizations: 1 rTSST-1v: 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 .		rTSST-1 Variant Candidate Vaccine 10µg Number of Immunizations: 2 rTSST-1v: 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 .		rTSST-1 Variant Candidate Vaccine 10µg Number of Immunizations: 3 rTSST-1v: 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 .		rTSST-1 Variant Candidate Vaccine 100µg Number of Immunizations: 1 rTSST-1v: 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 .		rTSST-1 Variant Candidate Vaccine 100µg Number of Immunizations: 2 rTSST-1v: 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 .		rTSST-1 Variant Candidate Vaccine 100 µg Number of Immunizations: 3 rTSST-1v: 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 .		Al(OH)3 Adjuvant, 1mg Number of Immunizations: 3 rTSST-1v: 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 .
All Cause Mortality
	Dose Group 1		Dose Group 2		Dose Group 3		Dose Group 4		Dose Group 5		Dose Group 6		Dose Group 7
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/20 (0%)		0/20 (0%)		0/20 (0%)		0/20 (0%)		0/20 (0%)		0/20 (0%)
Serious Adverse Events
	Dose Group 1		Dose Group 2		Dose Group 3		Dose Group 4		Dose Group 5		Dose Group 6		Dose Group 7
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/20 (0%)		0/20 (0%)		0/20 (0%)		1/20 (5%)		0/20 (0%)		0/20 (0%)
Blood and lymphatic system disorders
anaphylactic reaction	0/20 (0%)	0	0/20 (0%)	0	0/20 (0%)	0	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0
Other (Not Including Serious) Adverse Events
	Dose Group 1		Dose Group 2		Dose Group 3		Dose Group 4		Dose Group 5		Dose Group 6		Dose Group 7
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/20 (65%)		16/20 (80%)		14/20 (70%)		17/20 (85%)		16/20 (80%)		19/20 (95%)		14/20 (70%)
Gastrointestinal disorders
Gastrointestinal disorders	6/20 (30%)	6	7/20 (35%)	13	5/20 (25%)	10	8/20 (40%)	18	2/20 (10%)	2	5/20 (25%)	9	4/20 (20%)	8
Nausea	2/20 (10%)	2	5/20 (25%)	6	4/20 (20%)	6	5/20 (25%)	10	1/20 (5%)	1	3/20 (15%)	4	3/20 (15%)	4
General disorders
mild to moderate AE	13/20 (65%)	39	16/20 (80%)	29	14/20 (70%)	26	17/20 (85%)	53	16/20 (80%)	39	19/20 (95%)	40	14/20 (70%)	50
General disorders and administration site conditions	8/20 (40%)	23	11/20 (55%)	18	8/20 (40%)	15	13/20 (65%)	33	9/20 (45%)	23	10/20 (50%)	21	9/20 (45%)	24
Fatigue	6/20 (30%)	18	7/20 (35%)	10	4/20 (20%)	8	8/20 (40%)	15	5/20 (25%)	9	8/20 (40%)	10	8/20 (40%)	16
Influenza-like illness	2/20 (10%)	4	6/20 (30%)	7	3/20 (15%)	6	8/20 (40%)	12	6/20 (30%)	12	8/20 (40%)	9	4/20 (20%)	6
Infections and infestations
Infections and infestations	12/20 (60%)	19	11/20 (55%)	25	12/20 (60%)	22	10/20 (50%)	18	9/20 (45%)	13	9/20 (45%)	20	10/20 (50%)	21
Nasopharyngitis	5/20 (25%)	7	10/20 (50%)	18	6/20 (30%)	9	5/20 (25%)	6	7/20 (35%)	10	9/20 (45%)	16	6/20 (30%)	10
Injury, poisoning and procedural complications
Injury, poisoning and procedural complications	4/20 (20%)	4	3/20 (15%)	4	1/20 (5%)	1	4/20 (20%)	4	6/20 (30%)	8	3/20 (15%)	5	4/20 (20%)	4
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorders	7/20 (35%)	9	8/20 (40%)	10	5/20 (25%)	7	11/20 (55%)	17	12/20 (60%)	19	8/20 (40%)	16	6/20 (30%)	9
Myalgia	3/20 (15%)	3	4/20 (20%)	5	4/20 (20%)	4	6/20 (30%)	6	6/20 (30%)	9	5/20 (25%)	9	5/20 (25%)	8
Back pain	0/20 (0%)	0	1/20 (5%)	1	1/20 (5%)	1	4/20 (20%)	5	1/20 (5%)	1	2/20 (10%)	2	0/20 (0%)	0
Nervous system disorders
Nervos system disorders	7/20 (35%)	25	10/20 (50%)	26	9/20 (45%)	29	15/20 (75%)	81	11/20 (55%)	30	10/20 (50%)	21	10/20 (50%)	42
Headache	6/20 (30%)	24	9/20 (45%)	25	8/20 (40%)	27	13/20 (65%)	75	11/20 (55%)	30	10/20 (50%)	21	9/20 (45%)	40
Reproductive system and breast disorders
Reproductive system and breast disorders	1/20 (5%)	1	1/20 (5%)	1	1/20 (5%)	1	1/20 (5%)	1	2/20 (10%)	3	5/20 (25%)	11	0/20 (0%)	0
Dysmenorrhoea	1/20 (5%)	1	0/20 (0%)	0	0/20 (0%)	0	0/20 (0%)	0	1/20 (5%)	2	4/20 (20%)	10	0/20 (0%)	0
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders	2/20 (10%)	2	1/20 (5%)	1	5/20 (25%)	6	4/20 (20%)	5	5/20 (25%)	5	0/20 (0%)	0	1/20 (5%)	2
Oropharyngeal pain	1/20 (5%)	1	0/20 (0%)	0	4/20 (20%)	4	3/20 (15%)	3	2/20 (10%)	2	0/20 (0%)	0	1/20 (5%)	1
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders	2/20 (10%)	2	3/20 (15%)	3	4/20 (20%)	4	4/20 (20%)	5	6/20 (30%)	11	3/20 (15%)	3	2/20 (10%)	2
Surgical and medical procedures
Surgical and medical procedures	0/20 (0%)	0	1/20 (5%)	1	0/20 (0%)	0	2/20 (10%)	2	3/20 (15%)	5	0/20 (0%)	0	2/20 (10%)	2

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.