Amendment of rTSST-1 Variant Vaccine Phase 1 Clinical Trial

Phase 1

Completed

Conditions: Sepsis
Toxic-Shock Syndrome

Interventions: Biological: rTSST-1 Variant Candidate Vaccine

Registration Number: NCT02971670

Lead Sponsor: Biomedizinische Forschungs gmbH

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 23

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Dose Group 3	rTSST-1 Variant Candidate Vaccine	Treatment: rTSST-1 Variant Candidate Vaccine 30 µg
Dose Group 0	rTSST-1 Variant Candidate Vaccine	Control: Al(OH)3 Adjuvant
Dose Group 1	rTSST-1 Variant Candidate Vaccine	Treatment: rTSST-1 Variant Candidate Vaccine 3 µg
Dose Group 2	rTSST-1 Variant Candidate Vaccine	Treatment: rTSST-1 Variant Candidate Vaccine 10 µg

Primary Outcome Measures

Name	Time	Method
Persistence of TSST-1 Antibodies	6-15 months after last immunization of Phase I	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.
Number of Participants With Adverse Events as a Measure of Safety	through 6 months	Clinical observation and clinical laboratory values

Secondary Outcome Measures

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