Sepsis, Toxic-Shock Syndrome
Conditions
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.
Interventions
BIOLOGICALrTSST-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.
Sponsors
Medical University of Vienna
Biomedizinische Forschungs gmbH
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events as a Measure of Safety | through 6 months | Clinical observation and clinical laboratory values |
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dose Group 1 Treatment: rTSST-1 Variant Candidate Vaccine 3 µg
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. | 13 |
| Dose Group 2 Treatment: rTSST-1 Variant Candidate Vaccine 10 µg
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. | 2 |
| Dose Group 3 Treatment: rTSST-1 Variant Candidate Vaccine 30 µg
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. | 5 |
| Dose Group 0 Control: Al(OH)3 Adjuvant
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. | 3 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 4 | 1 | 1 | 2 |
Baseline characteristics
| Characteristic | Dose Group 2 | Dose Group 3 | Dose Group 1 | Dose Group 0 | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 5 Participants | 13 Participants | 3 Participants | 23 Participants |
| Age, Continuous | 45 years STANDARD_DEVIATION 18.4 | 28.6 years STANDARD_DEVIATION 7.9 | 38.5 years STANDARD_DEVIATION 10.1 | 31.3 years STANDARD_DEVIATION 10.7 | 35.9 years STANDARD_DEVIATION 10.9 |
| Region of Enrollment Austria | 2 Participants | 5 Participants | 13 Participants | 3 Participants | 23 Participants |
| Sex: Female, Male Female | 1 Participants | 4 Participants | 6 Participants | 3 Participants | 14 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 7 Participants | 0 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 7 / 9 | 1 / 1 | 1 / 4 | 0 / 1 |
| serious Total, serious adverse events | 1 / 9 | 0 / 1 | 0 / 4 | 0 / 1 |
Outcome results
Primary
Number of Participants With Adverse Events as a Measure of Safety
Clinical observation and clinical laboratory values
Time frame: through 6 months
Population: Out of 23 Subjects responding, 8 subjects were not interested to continue; 15 subjects were included as PP population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose Group 1 | Number of Participants With Adverse Events as a Measure of Safety | 7 participants |
| Dose Group 2 | Number of Participants With Adverse Events as a Measure of Safety | 1 participants |
| Dose Group 3 | Number of Participants With Adverse Events as a Measure of Safety | 1 participants |
| Dose Group 0 | Number of Participants With Adverse Events as a Measure of Safety | 0 participants |
Primary
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.
Time frame: 6-15 months after last immunization of Phase I
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose Group 1 | Persistence of TSST-1 Antibodies | 9 Participants |
| Dose Group 2 | Persistence of TSST-1 Antibodies | 2 Participants |
| Dose Group 3 | Persistence of TSST-1 Antibodies | 3 Participants |
| Dose Group 0 | Persistence of TSST-1 Antibodies | 0 Participants |
Secondary
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.
Time frame: through 6 months after third immunization
Population: Out of 23 Subjects responding, 8 subjects were not interested to continue; 15 subjects were included as PP population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose Group 1 | Boosterability of BioMed rTSST-1 Variant Vaccine | 8 Participants |
| Dose Group 2 | Boosterability of BioMed rTSST-1 Variant Vaccine | 1 Participants |
| Dose Group 3 | Boosterability of BioMed rTSST-1 Variant Vaccine | 4 Participants |
| Dose Group 0 | Boosterability of BioMed rTSST-1 Variant Vaccine | 0 Participants |