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Staphylococcus Aureus Toxoids Phase 1-2 Vaccine Trial

Primary Purpose

Staphylococcus Aureus

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Monovalent rAT

Monovalent rLukS-PV

Bivalent rLukS-PV / rAT

Placebo with adjuvant

Placebo

About this trial

This is an interventional prevention trial for Staphylococcus Aureus focused on measuring Staphylococcus aureus, Skin and soft tissue infection, Methicillin-resistant Staphylococcus aureus, Recombinant alpha-toxoid (rAT), Recombinant LukS subunit of Panton-Valentine Leukocidin (rLukS-PV)

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

Brooke Army Medical Center
Naval Medical Center Portsmouth

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Arm Label

Active Vaccine

Placebo with Alum

Saline Placebo

Arm Description

Monovalent rAT or Monovalent rLukS-PV or Bivalent rLukS-PV / rAT

Outcomes

Primary Outcome Measures

Assessment of Safety Through Clinical Examinations, Clinical Laboratory Results, Self-reported Diary Reactogenicity Data and Adverse Event Reports

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

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

Full Information

NCT ID

NCT01011335

First Posted

November 9, 2009

Last Updated

February 13, 2023

Sponsor

Henry M. Jackson Foundation for the Advancement of Military Medicine

Collaborators

Nabi Biopharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT01011335

Brief Title

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

2. Study Status

Record Verification Date

February 2023

Overall Recruitment Status

Completed

Study Start Date

November 2009 (undefined)

Primary Completion Date

March 2011 (Actual)

Study Completion Date

March 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Henry M. Jackson Foundation for the Advancement of Military Medicine

Collaborators

Nabi Biopharmaceuticals

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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)

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

176 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Active Vaccine

Arm Type

Experimental

Arm Description

Monovalent rAT or Monovalent rLukS-PV or Bivalent rLukS-PV / rAT

Arm Title

Placebo with Alum

Arm Type

Placebo Comparator

Arm Title

Saline Placebo

Arm Type

Placebo Comparator

Intervention Type

Biological

Intervention Name(s)

Monovalent rAT

Intervention Description

10, 25, 50 or 100 μg

Intervention Type

Biological

Intervention Name(s)

Monovalent rLukS-PV

Intervention Description

10, 25, 50 or 100 μg

Intervention Type

Biological

Intervention Name(s)

Bivalent rLukS-PV / rAT

Intervention Description

10, 25 or 50 μg

Intervention Type

Biological

Intervention Name(s)

Placebo with adjuvant

Intervention Description

Placebo with adjuvant

Intervention Type

Biological

Intervention Name(s)

Placebo

Intervention Description

Placebo saline

Primary Outcome Measure Information:

Title

Assessment of Safety Through Clinical Examinations, Clinical Laboratory Results, Self-reported Diary Reactogenicity Data and Adverse Event Reports

Description

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

Time Frame

Up to 6 months

Title

Immunogenicity: Geometric Mean Concentrations After First Injection, Completer Population

Description

Time Frame

Up to 3 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Michael L Landrum, MD

Organizational Affiliation

Infectious Disease Clinical Research Program, Uniformed Services University of the Health Sciences

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Paul Kessler, MD

Organizational Affiliation

Nabi Biopharmaceuticals

Official's Role

Principal Investigator

Facility Information:

Facility Name

Brooke Army Medical Center

City

Fort Sam Houston

State/Province

Texas

ZIP/Postal Code

78234

Country

United States

Facility Name

Naval Medical Center Portsmouth

City

Portsmouth

State/Province

Virginia

ZIP/Postal Code

23708

Country

United States

12. IPD Sharing Statement

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Staphylococcus Aureus Toxoids Phase 1-2 Vaccine Trial

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