rTSST-1 Variant Vaccine Phase 1 First-in-man Trail

NCT ID: NCT02340338

Last Updated: 2017-01-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 46 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-07-31
• Study Completion Date: 2015-07-31

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 aim of this study is to demonstrate the safety and tolerability of the BioMed recombinant toxic shock syndrome toxin (rTSST-1) Variant Vaccine in healthy adults. The second aim of the study is to measure antibodies in the blood of these healthy volunteers which have been produced in response to treatment with the BioMed rTSST-1 Variant Vaccine. These antibodies are expected to be important in resistance against the diseases. 46 healthy adults, male and female, age 18-64 years will be assigned to 6 dose groups of the vaccine at the Department of Clinical Pharmacology of the Medical University of Vienna. The patients will be monitored for vital signs, hematology, clinical chemistry, blood cytokine level and antibodies against TSST-1. Immunization will be repeated 4 weeks after the first with the same dose.

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, partly randomized, parallel control, dose escalation study of the safety and immunogenicity of the BioMed rTSST1 Variant Vaccine compared to adjuvant in healthy adults.

28 - 3 days prior to entry into the study, 50 male and female subjects 18 - 64 years in age will be screened for eligibility , screening criteria to 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. 46 of these subjects will be entered into the study.

In a first step, two subjects will receive the adjuvanted Vaccine containing 100 ng rTSST-1 Ag and one subject will receive the adjuvant containing 0.2 mg Al(0H)3 only (Group 1). The subjects will be seen four times after immunization in a period of 14 days (6 h, 48 h + 2 hrs, 7 + 1 days and 14 + 2 days).Tests and examinations will include vital signs, hematology and clinical chemistry parameters, C-reactive protein, cytokines, TSST-Ab , local reactions and adverse events.

In the absence of clinically relevant adverse events , another three subjects will be entered into the study one week later, two of them to receive the adjuvanted Vaccine containing 300 ng rTSST-1 Ag, one receiving the adjuvant containing 0.6 mg Al(0H)3 (Group 2) and be followed for a period of 14 days as described above.

In the absence of clinically relevant adverse events , four more subjects will be entered into the study one week thereafter, three of them to receive the adjuvanted Vaccine containing 1 µg rTSST-1 Ag , one to receive adjuvant containing 1 mg Al(0H)3 alone (Group 3), and be followed for a period of 14 days in the manner described above.

Immunization will be repeated at the same dose level in each group one to two months after the first. Follow-up will be the same.

If immunogenicity can be shown after the second administration of the Vaccine containing 1 µg of rTSST-1 Ag, doses and sample sizes will be increased to Vaccine containing 3 µg , 10 µg, and 30 µg and adjuvant containing 1 mg Al(0H)3 in nine and three subjects in Groups 4 - 6, respectively. Otherwise, the sample size of 3 + 1 will continue until immunogenicity is seen at a higher dose level.

Subjects in Groups 4 - 6 will receive a second immunization at the respective dose level one to two months after the first, follow-up being the same as in Groups 1 - 3.

If there is no immune response in any dose group after the second immunization, a third injection will be given 4 - 8 weeks thereafter in dose groups of 1 µg (Groups 3 - 6) and above.

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.

Subjects to receive vaccine containing 3 µg rTSST-1 Ag or more will be randomized.

Conditions

Toxic Shock Syndrome; Vaccination; Sepsis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Dose Group 1

Treatment: rTSST-1 Variant Candidate Vaccine 100 ng

Group Type: EXPERIMENTAL

rTSST-1 Variant Candidate Vaccine

Intervention Type: BIOLOGICAL

In the absence of adverse events classified as clinically relevant, interval between dose escalations 1 week. Immunization to be repeated at the same dose level 1 - 2 months later. If immunogenicity can be shown after the second administration of 1 µg, the sample size will be increased from 3 + 1 to 9 + 3. Otherwise, the sample size of 3 + 1 will continue until immunogenicity is seen at a higher dose level. If there is no immune response in any dose group after the second immunization, a third injection will be given 4 -8 weeks thereafter in dose groups of 1 µg and above.

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 .

Patients 3 µg or more will be randomized.

Dose Group 2

Treatment: rTSST-1 Variant Candidate Vaccine 300 ng

Group Type: EXPERIMENTAL

rTSST-1 Variant Candidate Vaccine

Intervention Type: BIOLOGICAL

In the absence of adverse events classified as clinically relevant, interval between dose escalations 1 week. Immunization to be repeated at the same dose level 1 - 2 months later. If immunogenicity can be shown after the second administration of 1 µg, the sample size will be increased from 3 + 1 to 9 + 3. Otherwise, the sample size of 3 + 1 will continue until immunogenicity is seen at a higher dose level. If there is no immune response in any dose group after the second immunization, a third injection will be given 4 -8 weeks thereafter in dose groups of 1 µg and above.

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 .

Patients 3 µg or more will be randomized.

Dose Group 3

Treatment: rTSST-1 Variant Candidate Vaccine 1 µg

Group Type: EXPERIMENTAL

rTSST-1 Variant Candidate Vaccine

Intervention Type: BIOLOGICAL

In the absence of adverse events classified as clinically relevant, interval between dose escalations 1 week. Immunization to be repeated at the same dose level 1 - 2 months later. If immunogenicity can be shown after the second administration of 1 µg, the sample size will be increased from 3 + 1 to 9 + 3. Otherwise, the sample size of 3 + 1 will continue until immunogenicity is seen at a higher dose level. If there is no immune response in any dose group after the second immunization, a third injection will be given 4 -8 weeks thereafter in dose groups of 1 µg and above.

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 .

Patients 3 µg or more will be randomized.

Dose Group 4

Treatment: rTSST-1 Variant Candidate Vaccine 3 µg

Group Type: EXPERIMENTAL

rTSST-1 Variant Candidate Vaccine

Intervention Type: BIOLOGICAL

In the absence of adverse events classified as clinically relevant, interval between dose escalations 1 week. Immunization to be repeated at the same dose level 1 - 2 months later. If immunogenicity can be shown after the second administration of 1 µg, the sample size will be increased from 3 + 1 to 9 + 3. Otherwise, the sample size of 3 + 1 will continue until immunogenicity is seen at a higher dose level. If there is no immune response in any dose group after the second immunization, a third injection will be given 4 -8 weeks thereafter in dose groups of 1 µg and above.

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 .

Patients 3 µg or more will be randomized.

Dose Group 5

Treatment: rTSST-1 Variant Candidate Vaccine 10 µg

Group Type: EXPERIMENTAL

rTSST-1 Variant Candidate Vaccine

Intervention Type: BIOLOGICAL

In the absence of adverse events classified as clinically relevant, interval between dose escalations 1 week. Immunization to be repeated at the same dose level 1 - 2 months later. If immunogenicity can be shown after the second administration of 1 µg, the sample size will be increased from 3 + 1 to 9 + 3. Otherwise, the sample size of 3 + 1 will continue until immunogenicity is seen at a higher dose level. If there is no immune response in any dose group after the second immunization, a third injection will be given 4 -8 weeks thereafter in dose groups of 1 µg and above.

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 .

Patients 3 µg or more will be randomized.

Dose Group 6

Treatment: rTSST-1 Variant Candidate Vaccine 30 µg

Group Type: EXPERIMENTAL

rTSST-1 Variant Candidate Vaccine

Intervention Type: BIOLOGICAL

In the absence of adverse events classified as clinically relevant, interval between dose escalations 1 week. Immunization to be repeated at the same dose level 1 - 2 months later. If immunogenicity can be shown after the second administration of 1 µg, the sample size will be increased from 3 + 1 to 9 + 3. Otherwise, the sample size of 3 + 1 will continue until immunogenicity is seen at a higher dose level. If there is no immune response in any dose group after the second immunization, a third injection will be given 4 -8 weeks thereafter in dose groups of 1 µg and above.

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 .

Patients 3 µg or more will be randomized.

Dose Group 0

Control: Al(OH)3 Adjuvant

Group Type: PLACEBO_COMPARATOR

rTSST-1 Variant Candidate Vaccine

Intervention Type: BIOLOGICAL

In the absence of adverse events classified as clinically relevant, interval between dose escalations 1 week. Immunization to be repeated at the same dose level 1 - 2 months later. If immunogenicity can be shown after the second administration of 1 µg, the sample size will be increased from 3 + 1 to 9 + 3. Otherwise, the sample size of 3 + 1 will continue until immunogenicity is seen at a higher dose level. If there is no immune response in any dose group after the second immunization, a third injection will be given 4 -8 weeks thereafter in dose groups of 1 µg and above.

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 .

Patients 3 µg or more will be randomized.

Interventions

rTSST-1 Variant Candidate Vaccine

In the absence of adverse events classified as clinically relevant, interval between dose escalations 1 week. Immunization to be repeated at the same dose level 1 - 2 months later. If immunogenicity can be shown after the second administration of 1 µg, the sample size will be increased from 3 + 1 to 9 + 3. Otherwise, the sample size of 3 + 1 will continue until immunogenicity is seen at a higher dose level. If there is no immune response in any dose group after the second immunization, a third injection will be given 4 -8 weeks thereafter in dose groups of 1 µg and above.

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 .

Patients 3 µg or more will be randomized.

Intervention Type: BIOLOGICAL

Eligibility Criteria

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
• signs and symptoms of relevant autoimmunity
• TSST-1 Ab titer > 1:2000

• 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, 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: DERIVED

PMID: 27296693 (View on PubMed)

Other Identifiers

BioMed0713

Identifier Type: -

Identifier Source: org_study_id