Evaluation of a Single Vaccination of One of Three Ascending Dose Levels of a 4-Antigen Staphylococcus Aureus Vaccine (SA4Ag) and a Single Dose Level of a 3-Antigen Staphylococcus Aureus Vaccine (SA3Ag) in Healthy Adults Aged 65 to <86 Years

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01643941
First received: July 9, 2012
Last updated: April 11, 2014
Last verified: April 2014
  Purpose

This is a Phase 1 and Phase 2 study of a single vaccination with one of three dose levels of a 4-antigen investigational vaccine against Staphylococcus aureus (SA4Ag) and a single dose level of a 3-antigen Staphylococcus aureus vaccine (SA3Ag). The main goal of the study is to determine how safe and well tolerated the vaccine is as well as to describe the immune response elicited by the vaccine in healthy adults aged 65 to <86 years. In addition, the study aims to assess the effect of the Staphylococcus aureus vaccine on the presence of the Staphylococcus aureus within the nose, throat and perineal skin of healthy adults aged 65 to <86 years.


Condition Intervention Phase
Staphylococcal Infections
Biological: SA4Ag vaccine low dose
Procedure: Blood draw
Procedure: Colonization swab sample
Biological: SA4Ag vaccine mid dose
Biological: SA4Ag vaccine high dose
Biological: SA3Ag vaccine
Procedure: Blood sample
Biological: Placebo
Procedure: Colonization swab samples
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Official Title: A Phase 1/2 Placebo-controlled, Randomized, Double-blind Trial to Evaluate the Safety, Tolerability and Immunogenicity of 3 Ascending Dose Levels of a 4-antigen Staphylococcus Aureus Vaccine (SA4Ag) and a Single Dose Level of a 3-antigen Staphylococcus Aureus Vaccine (SA3Ag) in Healthy Adults Aged 65 to < 86 Years

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Number and proportion of subjects reporting solicited local reactions (size of redness and/or swelling and severity of pain at the injection site) and severity of the local reactions as self-reported on electronic diaries (e-diaries) [ Time Frame: 14 days ] [ Designated as safety issue: Yes ]
  • Number and proportion of subjects reporting solicited systemic events (fever, vomiting, diarrhea, headache, fatigue, new or worsening muscle pain, new or worsening joint pain) and severity of solicited systemic events self-reported on electronic diaries [ Time Frame: 14 days ] [ Designated as safety issue: Yes ]
  • Number and proportion of subjects reporting unsolicited AEs and serious adverse events (SAEs) categorized according to the Medical Dictionary for Regulatory Activities (MedDRA) [ Time Frame: 1 month (AEs); 6 months (SAEs) ] [ Designated as safety issue: Yes ]
  • Number and proportion of Phase 1 subjects with abnormal hematology, coagulation and blood chemistry lab assessments [ Time Frame: 14 days ] [ Designated as safety issue: Yes ]
  • Number and proportion of Phase 1 subjects with grading shifts in hematology, coagulation and blood chemistry laboratory assessments [ Time Frame: 14 days ] [ Designated as safety issue: Yes ]
  • Proportion of subjects achieving antibody responses to specific vaccine components with results ≥ thresholds defined for each vaccine component based on immunoglobulin-binding and/or opsonphagocytic activity assays [ Time Frame: 1 month ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Immunoglobulin titers measured as geometric mean titers for each antigen at each applicable blood sampling time point, as measured by antigen-specific antibody levels using an immunoglobulin binding assay. [ Time Frame: various, up to 12 months ] [ Designated as safety issue: No ]
  • Opsonophagocytic activity titers measured as geometric mean titers against S. aureus isolates at each applicable blood sampling time point. [ Time Frame: various, up to 12 months ] [ Designated as safety issue: No ]
  • Immunoglobulin geometric mean fold rise for each of the vaccine components as measured by antigen-specific antibody levels using an immunoglobulin binding assay. [ Time Frame: 1 month ] [ Designated as safety issue: No ]
  • Geometric mean fold rise on opsonophagocytic activity assay titers against S. aureus isolates. [ Time Frame: 1 month ] [ Designated as safety issue: No ]
  • Proportion of subjects achieving antibody responses to specific antigens with results ≥ thresholds defined for each vaccine component at each applicable visit. [ Time Frame: Various, up to 12 months ] [ Designated as safety issue: No ]
  • Proportion of subjects with ≥2-fold, ≥4-fold, ≥8-fold, ≥16-fold, and ≥32-fold increase in immunoglobulin titers from baseline to each applicable visit after vaccination for each antigen. [ Time Frame: Various, up to 12 months ] [ Designated as safety issue: No ]
  • Proportion of subjects with ≥2-fold, ≥4-fold, ≥8-fold, ≥16-fold, and ≥32-fold increase in opsonophagocytic activity titers against S. aureus isolates from baseline to each applicable visit after vaccination. [ Time Frame: Various, up to 12 months ] [ Designated as safety issue: No ]

Enrollment: 284
Study Start Date: August 2012
Study Completion Date: March 2014
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
SA4Ag vaccine low dose
Biological: SA4Ag vaccine low dose
Subjects receive 1 intramuscular injection (0.5 mL) of the low dose level of the SA4Ag vaccine.
Procedure: Blood draw
Blood for HIV, HBV and HCV screening will be collected prior to enrollment for Phase 1 subjects. Blood for hematology, coagulation and blood chemistry will be collected at a minimum of 3 timepoints from Phase 1 subjects. Blood for immunogenicity will be collected from all subjects at various timepoints.
Procedure: Colonization swab sample
Colonization swabs will be collected from all subjects at various timepoints.
Experimental: 2
SA4Ag vaccine mid dose
Biological: SA4Ag vaccine mid dose
Subjects receive 1 intramuscular injection (0.5 mL) of the mid dose level of the SA4Ag vaccine.
Procedure: Blood draw
Blood for HIV, HBV and HCV screening will be collected prior to enrollment for Phase 1 subjects. Blood for hematology, coagulation and blood chemistry will be collected at a minimum of 3 timepoints from Phase 1 subjects. Blood for immunogenicity will be collected from all subjects at various timepoints.
Procedure: Colonization swab sample
Colonization swabs will be collected from all subjects at various timepoints.
Experimental: 3
SA4Ag vaccine high dose
Biological: SA4Ag vaccine high dose
Subjects receive 1 intramuscular injection (0.5 mL) of the high dose level of the SA4Ag vaccine.
Procedure: Blood draw
Blood for HIV, HBV and HCV screening will be collected prior to enrollment for Phase 1 subjects. Blood for hematology, coagulation and blood chemistry will be collected at a minimum of 3 timepoints from Phase 1 subjects. Blood for immunogenicity will be collected from all subjects at various timepoints.
Procedure: Colonization swab sample
Colonization swabs will be collected from all subjects at various timepoints.
Experimental: 4
SA3Ag vaccine
Biological: SA3Ag vaccine
Phase 2 only: Subjects receive 1 intramuscular injection (0.5 mL) of the mid dose level of the SA3Ag vaccine.
Procedure: Blood sample
Blood for immunogenicity will be collected from all subjects at various timepoints.
Procedure: Colonization swab sample
Colonization swabs will be collected from all subjects at various timepoints.
Placebo Comparator: 5
Placebo
Biological: Placebo
Subjects receive one intramuscular injection (0.5 mL) of placebo which contains excipients of the vaccine formulation minus the active ingredients.
Procedure: Blood draw
Blood for HIV, HBV and HCV screening will be collected prior to enrollment for Phase 1 subjects. Blood for hematology, coagulation and blood chemistry will be collected at a minimum of 3 timepoints from Phase 1 subjects. Blood for immunogenicity will be collected from all subjects at various timepoints.
Procedure: Colonization swab samples
Colonization swabs will be collected from all subjects at various timepoints.

  Eligibility

Ages Eligible for Study:   65 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy males and healthy postmenopausal females, aged 65 to <86 years at enrollment, as determined by medical history, physical examination, and the clinical judgment of the investigator to be eligible for the study. Subjects with preexisting chronic medical conditions determined to be stable may be included.
  • Available for the entire duration of the study, and able to comply with scheduled visits, study plan, laboratory tests, and other study procedures including completion of the electronic diary (e diary) from Day 1 to Day 14 following vaccination.
  • Able to be contacted by telephone during study participation.
  • Male subjects who, in the opinion of the investigator, are biologically capable of fathering children, and who are sexually active with women of childbearing potential must agree to use a highly effective method of contraception throughout the study.

Exclusion Criteria:

  • Unstable chronic medical condition or disease requiring significant change in therapy or hospitalization for worsening disease within 3 months before receipt of study vaccine.
  • Serious chronic medical disorders or any disorder that in the investigator's opinion precludes the subject from participating in the study.
  • Donation of blood volume of 250 mL or greater or donation of plasma within 3 months prior to enrollment through conclusion of the study.
  • Bleeding condition associated with prolonged bleeding time that may contraindicate intramuscular injection or blood draw including subjects taking anticoagulant, antiplatelet and/or antithrombotic agents except for low-dose daily aspirin within 30 days before enrollment through completion of Visit 6 (Day 29).
  • Any contraindication to vaccination or vaccine components, including previous anaphylactic reaction to any vaccine or vaccine related components.
  • Immunocompromised persons or subjects currently on immunosuppressive therapy or with a history of immunosuppressive therapy. History of immune-modifying drugs.
  • Previous administration of S. aureus vaccination.
  • Any infection proven or suspected to be caused by S. aureus within 6 months preceding study vaccination.
  • Receipt of blood products or immunoglobulins (including monoclonal antibodies) within 12 months before enrollment through conclusion of the study.
  • Participation in other investigational or interventional studies within 30 days before the current study begins and/or during study participation. Participation in purely observational studies is acceptable.
  • Subjects who are investigational site staff members or subjects who are immediate family members (first-degree relatives) of investigational site staff members or Pfizer employees directly involved in the conduct of the trial.
  • Residence in a nursing home or long-term care facility or requirement for semiskilled nursing care. An ambulatory subject who is a resident of a retirement home or village is eligible for the trial.
  • A Mini-Mental State Examination (MMSE) score of ≤21.
  • For Phase 1 subjects only, any abnormality in screening hematology, coagulation, and/or blood chemistry laboratory values except as noted in protocol
  • Subjects with known active disease with human immunodeficiency virus (HIV), hepatitis B virus (HBV), and/or hepatitis C virus (HCV), or Phase 1 subjects with a positive screening test for HIV, HBV and/or HCV.
  • Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
  • Planned surgical procedure within 30 days following vaccination.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01643941

Locations
United States, Florida
Pfizer Investigational Site
Hollywood, Florida, United States, 33024
Pfizer Investigational Site
South Miami, Florida, United States, 33143
United States, Kansas
Pfizer Investigational Site
Overland Park, Kansas, United States, 66212
United States, North Carolina
Pfizer Investigational Site
Cary, North Carolina, United States, 27518
United States, Ohio
Pfizer Investigational Site
Cincinnati, Ohio, United States, 45206
United States, Tennessee
Pfizer Investigational Site
Nashville, Tennessee, United States, 37232
United States, Texas
Pfizer Investigational Site
Austin, Texas, United States, 78705
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01643941     History of Changes
Other Study ID Numbers: B3451011
Study First Received: July 9, 2012
Last Updated: April 11, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
Staphylococcus aureus
vaccine
Staphylococcal infection

Additional relevant MeSH terms:
Staphylococcal Infections
Gram-Positive Bacterial Infections
Bacterial Infections

ClinicalTrials.gov processed this record on April 15, 2014