Staphylococcus Aureus Toxoids Phase 1-2 Vaccine Trial

Phase 1

Completed

Conditions: Staphylococcus Aureus

Interventions: Biological: Monovalent rAT
Biological: Placebo
Biological: Placebo with adjuvant
Biological: Monovalent rLukS-PV
Biological: Bivalent rLukS-PV / rAT

Registration Number: NCT01011335

Lead Sponsor: Henry M. Jackson Foundation for the Advancement of Military Medicine

Brief Summary: This study involves the use of investigational vaccines. A vaccine is a medicine that causes the body to make antibodies. Antibodies help destroy foreign substances that enter the body. The purpose of this study is to find the right dose of a new vaccine that is safe and produces a good immune response (how well your body recognizes and defends itself against harmful foreign substances). There are two Staphylococcus aureus toxoids (components or antigens) under investigation in this study; one of them is a protein known as rAT and the other is a protein known as rLukS-PV. They are being developed to see if they are effective at preventing infections caused by the bacteria Staphylococcus aureus.

Detailed Description: Staphylococcus aureus is a leading cause of skin and soft tissue infections. Antibiotic resistance, such as seen with new community-acquired methicillin-resistant strains, presents a major challenge in treating and preventing these infections. Therefore, a preventative vaccine is considered a potentially better approach.

This study assesses the safety and immunogenicity of monovalent and bivalent S. aureus vaccine components. Healthy adult subjects will be randomized to receive 1 dose of monovalent or bivalent toxoid vaccine, or placebo in a dose escalation schedule.

Antigen-specific antibody will be measured by ELISA in sera collected for three months after injection. Safety data will be collected as 7 day reactogenicity diaries after each injection, adverse events and Staphylococcus aureus and skin and soft tissue infections will be collected through Day 84, and serious adverse events and chronic illnesses will be collected for the full 6 month study period.

To evaluate the possible utility of booster doses, the cohort receiving the highest dose of bivalent antigen will have a 2nd dose administered at Day 84, with a new 7-day reactogenicity diary and sera collected after the 2nd dose. All subjects will be followed up with a 6 month phone call after vaccination or booster.

The total subject observation period will be for 24 weeks from Day 0, plus 12 additional weeks for the cohorts that receive a 2nd dose. With a recruitment period of 4 months, the study duration is expected to be approximately 13 months.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 176

Inclusion Criteria

Healthy adult males or females, DoD beneficiaries, including active duty members, 18-55 years of age.
Negative urine pregnancy test for female subjects of child bearing potential (negative test within 24 hours prior to investigational product injection) or documented surgical sterility.
Female subjects of child-bearing potential must use an acceptable method of birth control, as determined by the PI.
Willingness to participate in this study as evidenced by written informed consent.

Exclusion Criteria

Prior receipt of S. aureus rAT or rLukS-PV
Known S. aureus infection requiring medical treatment within the 3 months prior to investigational drug product injection
Known active viral or bacterial infection
Seropositivity for HIV infection
Known or suspected abuse of prescribed or illicit drugs, or alcohol in the past year
Use of any new medications (except oral contraceptives, over-the-counter medications, or vitamin supplements) within the 7 days prior to investigational drug product injection
Use of investigational drugs, vaccines, or devices during the study or within the 30 days prior to each dose of investigational drug product injection, or anticipated use of such items during the study
Use of systemic steroids (any dose) or high daily dose inhaled steroids within the last month. Use of low or medium daily dose inhaled, intranasal, or low potency topical steroid creams/ointments is allowed unless such medication was begun within the previous 7 days.
History of a bleeding or coagulation disorder; or use of anti-coagulant medications within 7 days prior to investigational product injection
Actively breastfeeding
Presence of grade I or higher abnormality in laboratory or vital signs parameter at time of screening
Presence of any condition which, in the opinion of the investigator, places the subject at undue risk or potentially jeopardizes the quality of the data to be generated

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Active Vaccine	Bivalent rLukS-PV / rAT	Monovalent rAT or Monovalent rLukS-PV or Bivalent rLukS-PV / rAT
Active Vaccine	Monovalent rLukS-PV	Monovalent rAT or Monovalent rLukS-PV or Bivalent rLukS-PV / rAT
Active Vaccine	Monovalent rAT	Monovalent rAT or Monovalent rLukS-PV or Bivalent rLukS-PV / rAT
Saline Placebo	Placebo	-
Placebo with Alum	Placebo with adjuvant	-

Primary Outcome Measures

Name	Time	Method
Assessment of Safety Through Clinical Examinations, Clinical Laboratory Results, Self-reported Diary Reactogenicity Data and Adverse Event Reports	Up to 6 months	Adverse events, local reactogenicity, and systemic reactogenicity were assessed through clinical examination by study providers, clinical lab results, as well as review of subject-completed diary
Immunogenicity: Geometric Mean Concentrations After First Injection, Completer Population	Up to 3 months	Immunogenicity is the ability of a particular substance, such as an antigen or epitope, to provoke an immune response in the body of a human or animal. Immunogenicity was determined on the basis of anti-rAT and anti-rLukS-PV IgG concentrations assessed by enzyme-linked immunosorbent assay (ELISA) in sera from blood samples collected on Days 0 (baseline), 14, 28 and 84 for those receiving a single dose of vaccine. For those receiving a second dose of vaccine, immunogenicity assessments were also conducted on Days 98 and 112. Immunogenicity was evaluated using the following metrics: geometric mean concentrations (GMCs), geometric mean fold increase (GMFIs) and seroresponse status. Seroresponse variables are normally defined in terms of exceeding a threshold.

Secondary Outcome Measures

Name	Time	Method

Trial Locations

Locations (2): Brooke Army Medical Center
🇺🇸
Fort Sam Houston, Texas, United States
Naval Medical Center Portsmouth
🇺🇸
Portsmouth, Virginia, United States