Amendment of rTSST-1 Variant Vaccine Phase 1 Clinical Trial

Amendment of 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 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.

Study Overview

• Status: Completed
• Conditions: Sepsis; Toxic-Shock Syndrome
• Intervention / Treatment: Biological: rTSST-1 Variant Candidate 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.

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Group 1; Treatment: rTSST-1 Variant Candidate Vaccine 3 µg	Biological: rTSST-1 Variant Candidate Vaccine; 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.
Experimental: Dose Group 2; Treatment: rTSST-1 Variant Candidate Vaccine 10 µg	Biological: rTSST-1 Variant Candidate Vaccine; 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.
Experimental: Dose Group 3; Treatment: rTSST-1 Variant Candidate Vaccine 30 µg	Biological: rTSST-1 Variant Candidate Vaccine; 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.
Placebo Comparator: Dose Group 0; Control: Al(OH)3 Adjuvant	Biological: rTSST-1 Variant Candidate Vaccine; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Biomedizinische Forschungs gmbH
• Collaborators: Medical University of Vienna
• Investigators: Study Director: Martha M Eibl, MD, Biomedizinische ForschungsgmbH

Study record dates

Study Major Dates

• Study Start: October 1, 2015
• Primary Completion (Actual): March 1, 2016
• Study Completion (Actual): May 1, 2016

Study Registration Dates

• First Submitted: November 21, 2016
• First Submitted That Met QC Criteria: November 21, 2016
• First Posted (Estimate): November 23, 2016

Study Record Updates

• Last Update Posted (Actual): June 9, 2017
• Last Update Submitted That Met QC Criteria: May 12, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Shock, Septic; Shock
• Other Study ID Numbers: BioMed0713 B

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes