Clinical trial NCT01011335: Staphylococcus Aureus Toxoids Phase 1-2 Vaccine Trial
Official title: A Randomized, Multi-Center Trial to Evaluate the Safety & Immunogenicity of Staphylococcus Aureus Toxoids, rAT and rLukS-PV, in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Staphylococcus Aureus
Keywords: Staphylococcus aureus
Skin and soft tissue infection
Methicillin-resistant Staphylococcus aureus
Recombinant alpha-toxoid (rAT)
Recombinant LukS subunit of Panton-Valentine Leukocidin (rLukS-PV)
Lead sponsor: Henry M. Jackson Foundation for the Advancement of Military Medicine
Sponsor class: OTHER
Collaborators: name: Nabi Biopharmaceuticals
First posted: 2009-11-11
Enrollment: 176
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Assessment of Safety Through Clinical Examinations, Clinical Laboratory Results, Self-reported Diary Reactogenicity Data and Adverse Event Reports
timeFrame: Up to 6 months
measure: Immunogenicity: Geometric Mean Concentrations After First Injection, Completer Population
timeFrame: Up to 3 months
Secondary outcomes:
Other outcomes:
Locations:
city: Fort Sam Houston
country: United States
facility: Brooke Army Medical Center
state: Texas
city: Portsmouth
country: United States
facility: Naval Medical Center Portsmouth
state: Virginia
Study officials:
affiliation: Infectious Disease Clinical Research Program, Uniformed Services University of the Health Sciences
name: Michael L Landrum, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Nabi Biopharmaceuticals
name: Paul Kessler, MD
role: PRINCIPAL_INVESTIGATOR
References: