An Evaluation Of Three Dose Levels Of 3-Antigen Staphylococcus Aureus Vaccine (SA3Ag) In Healthy Adults

Study Overview
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Brief Summary
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This study is a first-in-human (Phase 1) study using three dose levels of an investigational vaccine directed against Staphylococcus aureus (SA3Ag). This study is primarily designed to assess how safe and well tolerated SA3Ag is, but will also describe the immune response over 12 months elicited by SA3Ag. Additionally, this study will assess the effect of SA3Ag vaccine on the number of Staphylococcus aureus bacteria that naturally occur on the skin and within the nose and throat.

Official Title
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A Phase 1 Trial To Evaluate The Safety, Tolerability, And Immunogenicity Of 3 Ascending Dose Levels Of A 3-Antigen Staphylococcus Aureus Vaccine (SA3Ag) In Healthy Adults

Conditions
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Bacterial Infections, Staphylococcal Vaccines, Immunotherapy, Active, Staphylococcal Skin Infections, Staphylococcal Infections

Intervention / Treatment
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* Biological: SA3Ag vaccine
* Procedure: Blood draw
* Procedure: Colonization swab samples
* Biological: SA3Ag followed by Placebo
* Procedure: Blood draw
* Procedure: Colonization swab samples
* Biological: Placebo
* Procedure: Blood draw
* Procedure: Colonization swab samples
* Biological: SA3Ag with no booster in stage 2
* Procedure: Blood draw
* Procedure: Colonization swab samples
* Procedure: Placebo with no booster in stage 2
* Procedure: Blood draw
* Procedure: Colonization swab samples


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adults aged 18 to 24 years or 50 to 85 years who are available for the entire duration of the study, able to be contacted by phone, and able to complete all study procedures, including completion of an electronic diary (e-diary). Men and women who are able to have children, must use a reliable method of birth control for the duration of the study. Exclusion Criteria: Any major illness that would substantially increase the risk associated with participation in the study, or interfere with the evaluation of the study objectives - this is determined by the local physician. Donation of 250 mL or more of blood within the last 3 months. Condition associated with prolonged bleeding time, including subjects taking anticoagulant medication or antiplatelet therapy. Any contraindication to vaccination or vaccine components. Immunocompromised persons and subjects who receive treatment with immunosuppressive therapy. Previous administration of S. aureus vaccination. Receipt of blood products or immunoglobulins within 12 months prior to study Participation in another trial (not including observational trials) within the last 30 days. Study site personnel or immediate family members (first-degree relatives). Women who are pregnant (as determined by urine pregnancy test) or breast-feeding. Residence in a nursing home or long-term care facility or requirement for semiskilled nursing care. For subjects aged 65 years or older, a Mini-Mental State Examination (MMSE) score of <=21.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>SA3Ag in both stage 1 and stage 2 | Biological: SA3Ag vaccine<br>* In stage 1, each subject will receive 1 injection (0.5 mL) of one of the following doses: Low dose level 10 μg of CP5 and CP8 and 20 μg of rClfAm Mid-dose level 30 μg of CP5 and CP8 and 60 μg of rClfAm High dose level 100 μg of CP5 and CP8 and 200 μg of rClfAm In stage 2 the subject will receive 0.5 mL IM of the same dose level he/she received in stage 1.<br>Procedure: Blood draw<br>* Blood for immunogenicity will be taken at timepoints throughout stage 1 and stage 2. Blood for hematology will be done in a select subset of subjects in stage 1.<br>Procedure: Colonization swab samples<br>* Colonization swabs will be taken at timepoints throughout stage 1 and stage 2.<br>|
| Experimental: 2<br>SA3Ag in stage 1 followed by placebo in stage 2. | Biological: SA3Ag followed by Placebo<br>* In stage 1, each subject will receive 1 injection (0.5 mL) of one of the following doses: Low dose level 10 μg of CP5 and CP8 and 20 μg of rClfAm Mid-dose level 30 μg of CP5 and CP8 and 60 μg of rClfAm High dose level 100 μg of CP5 and CP8 and 200 μg of rClfAm In stage 2 the subject will receive one injection of 0.5 mL IM of the placebo.<br>Procedure: Blood draw<br>* Blood for immunogenicity will be taken at timepoints throughout stage 1 and stage 2. Blood for hematology will be done in a select subset of subjects in stage 1.<br>Procedure: Colonization swab samples<br>* Colonization swabs will be taken at timepoints throughout stage 1 and stage 2.<br>|
| Placebo Comparator: 3<br>Placebo in both stage 1 and stage 2 | Biological: Placebo<br>* In both stage 1 and stage 2, recipients will receive one injection (0.5 mL) IM of 150 mM (isotonic) NaCl for a total of 2 injections throughout the study.<br>Procedure: Blood draw<br>* Blood for immunogenicity will be taken at timepoints throughout stage 1 and stage 2. Blood for hematology will be done in a select subset of subjects in stage 1.<br>Procedure: Colonization swab samples<br>* Colonization swabs will be taken at timepoints throughout stage 1 and stage 2.<br>|
| Experimental: 4<br>SA3Ag in stage 1 and no vaccine in stage 2. | Biological: SA3Ag with no booster in stage 2<br>* In stage 1, each subject will receive 1 injection (0.5 mL) of one of the following doses: Low dose level 10 μg of CP5 and CP8 and 20 μg of rClfAm Mid-dose level 30 μg of CP5 and CP8 and 60 μg of rClfAm High dose level 100 μg of CP5 and CP8 and 200 μg of rClfAm In stage 2 the subject will receive no vaccine.<br>Procedure: Blood draw<br>* Blood for immunogenicity will be taken at timepoints throughout stage 1 and stage 2. Blood for hematology will be done in a select subset of subjects in stage 1.<br>Procedure: Colonization swab samples<br>* Colonization swabs will be taken at timepoints throughout stage 1 and stage 2.<br>|
| Placebo Comparator: 5<br>Placebo in stage 1 and no vaccine in stage 2. | Procedure: Placebo with no booster in stage 2<br>* In stage 1, recipients will receive one injection (0.5 mL) IM of 150 mM (isotonic) NaCl. In stage 2 the subject will receive no vaccine.<br>Procedure: Blood draw<br>* Blood for immunogenicity will be taken at timepoints throughout stage 1 and stage 2. Blood for hematology will be done in a select subset of subjects in stage 1.<br>Procedure: Colonization swab samples<br>* Colonization swabs will be taken at timepoints throughout stage 1 and stage 2.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary immunogenicity endpoint in stage 1 is antigen-specific antibody levels using an Ig binding assay (Ig titers) 28 days after vaccination at visit 1 in the 50- to 85-year age stratum at each vaccine group (3 SA3Ag dose levels and placebo). |  | 1 month | 
| The primary comparison of interest is a 2-fold increase in Ig titers relative to baseline for each antigen. |  | 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The secondary immunogenicity endpoints are Ig titers for each antigen (CP5, CP8, and rClfAm) 28 days after vaccination in the 18- to 24-year age stratum at each dose level cohort. |  | 1 month | 
| Ig titers for each antigen 28 days after the booster dose. |  | 7 months | 
| The safety endpoints are solicited and unsolicited AEs, SAEs, and hematologic and urine parameters. |  | 12 months | 
| OPA titers for each antigen 28 days after vaccination in both age strata at selected dose level cohort(s). |  | 1 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Staphylococcus aureus, Vaccine