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

NCT ID: NCT02814708

Last Updated: 2022-01-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 140 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-05-31
• Study Completion Date: 2021-01-31

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.

Conditions

Toxic Shock Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Dose Group 1

rTSST-1 Variant Candidate Vaccine 10µg Number of Immunizations: 1

Group Type: EXPERIMENTAL

rTSST-1v

Intervention Type: BIOLOGICAL

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 .

Dose Group 2

rTSST-1 Variant Candidate Vaccine 10µg Number of Immunizations: 2

Group Type: EXPERIMENTAL

rTSST-1v

Intervention Type: BIOLOGICAL

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 .

Dose Group 3

rTSST-1 Variant Candidate Vaccine 10µg Number of Immunizations: 3

Group Type: EXPERIMENTAL

rTSST-1v

Intervention Type: BIOLOGICAL

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 .

Dose Group 4

rTSST-1 Variant Candidate Vaccine 100µg Number of Immunizations: 1

Group Type: EXPERIMENTAL

rTSST-1v

Intervention Type: BIOLOGICAL

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 .

Dose Group 5

rTSST-1 Variant Candidate Vaccine 100µg Number of Immunizations: 2

Group Type: EXPERIMENTAL

rTSST-1v

Intervention Type: BIOLOGICAL

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 .

Dose Group 6

rTSST-1 Variant Candidate Vaccine 100 µg Number of Immunizations: 3

Group Type: EXPERIMENTAL

rTSST-1v

Intervention Type: BIOLOGICAL

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 .

Dose Group 7

Al(OH)3 Adjuvant, 1mg Number of Immunizations: 3

Group Type: PLACEBO_COMPARATOR

rTSST-1v

Intervention Type: BIOLOGICAL

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 .

Interventions

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 .

Intervention Type: BIOLOGICAL

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 64 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Medical University of Vienna

OTHER

Sponsor Role: collaborator

Biomedizinische Forschungs gmbH

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Martha M Eibl, MD

Role: STUDY_DIRECTOR

Biomedizinische Forschungsgmbh

Bernd Jilma, MD

Role: PRINCIPAL_INVESTIGATOR

Medical University of Vienna

Locations

Medical University of Vienna Department of Clinical Pharmacology

Vienna, , Austria

Countries

Austria

References

Schwameis M, Roppenser B, Firbas C, Gruener CS, Model N, Stich N, Roetzer A, Buchtele N, Jilma B, Eibl MM. Safety, tolerability, and immunogenicity of a recombinant toxic shock syndrome toxin (rTSST)-1 variant vaccine: a randomised, double-blind, adjuvant-controlled, dose escalation first-in-man trial. Lancet Infect Dis. 2016 Sep;16(9):1036-1044. doi: 10.1016/S1473-3099(16)30115-3. Epub 2016 Jun 10.

Reference Type: RESULT

PMID: 27296693 (View on PubMed)

Schoergenhofer C, Gelbenegger G, Hasanacevic D, Schoner L, Steiner MM, Firbas C, Buchtele N, Derhaschnig U, Tanzmann A, Model N, Larcher-Senn J, Drost M, Eibl MM, Roetzer A, Jilma B. A randomized, double-blind study on the safety and immunogenicity of rTSST-1 variant vaccine: phase 2 results. EClinicalMedicine. 2024 Jan 5;67:102404. doi: 10.1016/j.eclinm.2023.102404. eCollection 2024 Jan.

Reference Type: DERIVED

PMID: 38274114 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

BioMed 0515

Identifier Type: -

Identifier Source: org_study_id