Toxic Shock SyndromePhase 2NCT02814708
Clinical Trial of the BioMed rTSST-1 Variant Vaccine in Healthy Adults
A Phase 2 study testing rTSST-1v in people with Toxic Shock Syndrome, run by Biomedizinische Forschungs gmbH at 1 site in Austria.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 64 yearsHealthy volunteers can take part
- Conditions the study is for
- Toxic Shock Syndrome
- What is being tested?
- rTSST-1v
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 140 participants
- Where
- 1 siteAustria
- Study dates
- May 2016to Jan 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 64 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Austria1 site
Medical University of Vienna Department of Clinical Pharmacology
Vienna, 1090
About this study
Official title: Phase 2 Clinical Trial of the BioMed rTSST-1 Variant Vaccine in Healthy Adults
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%).
Read the 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
- Being tested
- rTSST-1v
- Keywords
- Sepsis, Vaccination
- Medical subject headings
- Shock, Septic, Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rTSST-1vBiological
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 .
| Study group | Role | What they receive |
|---|---|---|
| Dose Group 1 | Experimental | rTSST-1 Variant Candidate Vaccine 10µg Number of Immunizations: 1 Receives: Biological: rTSST-1v |
| Dose Group 2 | Experimental | rTSST-1 Variant Candidate Vaccine 10µg Number of Immunizations: 2 Receives: Biological: rTSST-1v |
| Dose Group 3 | Experimental | rTSST-1 Variant Candidate Vaccine 10µg Number of Immunizations: 3 Receives: Biological: rTSST-1v |
| Dose Group 4 | Experimental | rTSST-1 Variant Candidate Vaccine 100µg Number of Immunizations: 1 Receives: Biological: rTSST-1v |
| Dose Group 5 | Experimental | rTSST-1 Variant Candidate Vaccine 100µg Number of Immunizations: 2 Receives: Biological: rTSST-1v |
| Dose Group 6 | Experimental | rTSST-1 Variant Candidate Vaccine 100 µg Number of Immunizations: 3 Receives: Biological: rTSST-1v |
| Dose Group 7 | Placebo comparator | Al(OH)3 Adjuvant, 1mg Number of Immunizations: 3 Receives: Biological: rTSST-1v |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants (Percentage) With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment
Measured: 12 months and 18 months follow up
Secondary outcomes (1)
Number of Participants With a Fold Increase of ELISA IgG Against rTSST-1
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.
Measured: 12 months and 18 months follow up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jun 2016 (estimated)
- Study startMay 2016
- Primary completionMay 2020
- Study completionJan 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Toxic Shock SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- 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.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 140 participants (actual)
Sponsor and investigators
- Lead sponsor
- Biomedizinische Forschungs gmbH
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Medical University of Vienna
- Responsible party
- Sponsor
- Investigators
- Martha M Eibl, MD, Study director, Biomedizinische ForschungsgmbhBernd Jilma, MD, Principal investigator, Medical University of Vienna
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02814708
- Sponsor's protocol ID
- BioMed 0515
- Status last verified
- Dec 2021
- First submitted
- 21 Jun 2016
- Last updated
- 4 Jan 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 27296693Schoergenhofer 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.
PubMed 38274114
Study at a glance
From the registry record, last updated by the sponsor on 4 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2 Clinical Trial of the BioMed rTSST-1 Variant Vaccine in Healthy Adults
- ClinicalTrials.gov ID
- NCT02814708
- Acronym / sponsor ID
- BioMed 0515
- Conditions
- Toxic Shock Syndrome
- Keywords
- Sepsis, Vaccination
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 140 participants (actual)
- Lead sponsor
- Biomedizinische Forschungs gmbHIndustry (pharma, biotech, devices)
- Collaborators
- Medical University of Vienna
- Study start
- May 2016
- Primary completion
- May 2020 (actual)
- Study completion
- Jan 2021 (actual)
- First posted
- 28 Jun 2016 (estimated)
- Results
- Posted 13 Dec 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 7
- 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.
| Arm | Type | Receives |
|---|---|---|
| Dose Group 1 | Experimental | Biological: rTSST-1vrTSST-1 Variant Candidate Vaccine 10µg Number of Immunizations: 1 |
| Dose Group 2 | Experimental | Biological: rTSST-1vrTSST-1 Variant Candidate Vaccine 10µg Number of Immunizations: 2 |
| Dose Group 3 | Experimental | Biological: rTSST-1vrTSST-1 Variant Candidate Vaccine 10µg Number of Immunizations: 3 |
| Dose Group 4 | Experimental | Biological: rTSST-1vrTSST-1 Variant Candidate Vaccine 100µg Number of Immunizations: 1 |
| Dose Group 5 | Experimental | Biological: rTSST-1vrTSST-1 Variant Candidate Vaccine 100µg Number of Immunizations: 2 |
| Dose Group 6 | Experimental | Biological: rTSST-1vrTSST-1 Variant Candidate Vaccine 100 µg Number of Immunizations: 3 |
| Dose Group 7 | Placebo comparator | Biological: rTSST-1vAl(OH)3 Adjuvant, 1mg Number of Immunizations: 3 |
Who may qualify
- Ages
- 18 to 64 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| rTSST-1vEach 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 . | Biological | Dose Group 1, Dose Group 2, Dose Group 3, Dose Group 4, Dose Group 5, Dose Group 6, Dose Group 7 |
Primary outcome
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
1 secondary outcome
Number of Participants With a Fold Increase of ELISA IgG Against rTSST-1
Time frame: 12 months and 18 months follow up
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jan 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 27296693Schwameis 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.
- Derived from this study: PubMed 38274114Schoergenhofer 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.
Related trials for Toxic Shock Syndrome
Enrolling by invitation
Continuous Temperature Monitoring (CTM) for Cytokine Release Syndrome (CRS), an Immune-Related Adverse Event
Cytokine Release Syndrome, Neoplasms
RecruitingPhase 2
Outpatient Administration of Teclistamab or Talquetamab for Multiple Myeloma
Multiple Myeloma
RecruitingObservational study
Impact of Internal Menstrual Protections on Immunity and Vaginal Microbiota
Sexual Transmitted Disease, Vaginosis, Bacterial
RecruitingPhase 1
Adjunctive Methylene Blue for Immunotherapy-related CRS and ICANS: Phase I Study
Cytokine Release Syndrome, ICANS
RecruitingObservational study
Prodromes of Menstrual Staphylococcal Toxic Shock
Toxic Shock Syndrome Staphylococcal
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Martha M Eibl, MD study director
Biomedizinische Forschungsgmbh
Bernd Jilma, MD principal investigator
Medical University of Vienna
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing rTSST-1v in people with Toxic Shock Syndrome, run by Biomedizinische Forschungs gmbH at 1 site in Austria.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Austria. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Dec 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02814708, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jan 2022.