Amendment of rTSST-1 Variant Vaccine Phase 1 Clinical Trial

Study Overview
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Brief Summary
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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 Phase I study BioMed0713 demonstrated the safety and tolerability of the BioMed recombinant toxic shock syndrome toxin (rTSST-1) Variant Vaccine in healthy adults. The aim of this amendment is to demonstrate prolonged safety of the BioMed rTSST-1 Variant Vaccine and to assess persistence of antibodies generated in participants. The second aim of the study is to assess boosterability of the BioMed rTSST-1 Variant Vaccine.

Detailed Description
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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, single-blinded follow-up study of the safety and immunogenicity of the BioMed rTSST1 Variant Vaccine compared to adjuvant in healthy adults. All subjects who received 2 doses of 100 ng or more of the rTSST-1 Variant Candidate Vaccine or placebo (Groups 1 - 6) will be followed up in a single-blinded manner for long-term immunogenicity 6 - 15 months after their last (= second) immunization to gain more data about persistence of TSST-1 Ab titer. As this part of the study occurs after unblinding of the study subjects, it is termed Part B (for better discrimination from double-blinded Part A). All participants will be invited for a blood withdrawal to determine TSST-1 antibodies. Independent of the TSST-1 Ab titer level, subjects will receive one booster immunization either according to their former allocated dose (group 4: 3µg or placebo, group 5: 10 µg or placebo, group 6: 30 µg or placebo) or 3µg or placebo (groups 1 - 3) in the same visit. Placebo will be administered according to the former allocated dose. The treated subjects will stay two hours after immunization at the department and will be followed up for 6 months. Rationale for reduced monitoring after immunization and follow up: The BioMed rTSST-1 Variant Vaccine demonstrated excellent local and systemic tolerability and safety and an absence of adverse events classified as clinically relevant during the conduct of the study. Therefore no abnormal findings are expected and the monitoring of the vaccinated subjects after immunization is reduced to two hours, there are three follow up visits planned, 24h (+-2 h), 28 days (+-7 days) and 6 months (+-28 days) after booster vaccination.

Official Title
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Amendment of Phase 1 Clinical Trial of the BioMed rTSST-1 Variant Vaccine in Healthy Adults

Conditions
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Toxic-Shock Syndrome, Sepsis

Intervention / Treatment
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* Biological: rTSST-1 Variant Candidate Vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: male and female 18 - 64 years written informed consent physical exam: no abnormal findings unless considered irrelevant by the investigator uneventful medical history females: adequate contraception Exclusion Criteria: pregnancy positive virology markers at first screening signs and symptoms of relevant autoimmunity

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Group 1<br>Treatment: rTSST-1 Variant Candidate Vaccine 3 µg | Biological: rTSST-1 Variant Candidate Vaccine<br>* Immunization either according to their former allocated dose (group 4: 3 µg of candidate vaccine or placebo, group 5: 10 µg of candidate vaccine or placebo, group 6: 30 µg of candidate vaccine or placebo) or 3 µg of candidate vaccine or placebo (groups 1 - 3) from Phase I.<br>|
| Experimental: Dose Group 2<br>Treatment: rTSST-1 Variant Candidate Vaccine 10 µg | Biological: rTSST-1 Variant Candidate Vaccine<br>* Immunization either according to their former allocated dose (group 4: 3 µg of candidate vaccine or placebo, group 5: 10 µg of candidate vaccine or placebo, group 6: 30 µg of candidate vaccine or placebo) or 3 µg of candidate vaccine or placebo (groups 1 - 3) from Phase I.<br>|
| Experimental: Dose Group 3<br>Treatment: rTSST-1 Variant Candidate Vaccine 30 µg | Biological: rTSST-1 Variant Candidate Vaccine<br>* Immunization either according to their former allocated dose (group 4: 3 µg of candidate vaccine or placebo, group 5: 10 µg of candidate vaccine or placebo, group 6: 30 µg of candidate vaccine or placebo) or 3 µg of candidate vaccine or placebo (groups 1 - 3) from Phase I.<br>|
| Placebo Comparator: Dose Group 0<br>Control: Al(OH)3 Adjuvant | Biological: rTSST-1 Variant Candidate Vaccine<br>* Immunization either according to their former allocated dose (group 4: 3 µg of candidate vaccine or placebo, group 5: 10 µg of candidate vaccine or placebo, group 6: 30 µg of candidate vaccine or placebo) or 3 µg of candidate vaccine or placebo (groups 1 - 3) from Phase I.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events as a Measure of Safety | Clinical observation and clinical laboratory values | through 6 months | 
| Persistence of TSST-1 Antibodies | ELISA IgG against rTSST-1. Persistence of antibody was defined as a >/= 4-fold increase in TSST-1 Ab titer as compared to pre-vaccination values. | 6-15 months after last immunization of Phase I | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Boosterability of BioMed rTSST-1 Variant Vaccine | ELISA IgG against rTSST-1. Boosterability was defined as an increase in TSST-1 Ab titer as compared to antibody titers after second vaccination. | through 6 months after third immunization |