Evaluation of a Single Vaccination With One of Three Ascending Dose Levels of a 4-Antigen Staphylococcus Aureus Vaccine (SA4Ag) in Healthy Adults Aged 18 to <65 Years

NCT01364571 | Completed Phase 1 DMC

• 2 other identifiers: B34510016123K1-1005
• Study Type: interventional
• Target: 456
• Locations: 1 country
• Sites: 16

Brief Summary

This is a first-in-human (Phase 1) and Phase 2 study of a single vaccination with one of three dose levels of an investigational vaccine against Staphylococcus aureus (SA4Ag). 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 18 to \<65 years. In addition, the study aims to assess the effect of the SA4Ag vaccine on the presence of the Staphylococcus aureus on the skin and within the nose, throat and perineum of healthy adults aged 18 to \<65 years.

Conditions

Staphylococcal Infections

Keywords

Staphylococcus aureus; vaccine; staphylococcal infection

Outcome Measures

Primary Outcomes (5)

• Number and proportion of subjects reporting 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)

  14 days

• 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

  14 days

• Number and proportion of subjects reporting unsolicited AEs and serious adverse events (SAEs) categorized according to the Medical Dictionary for Regulatory Activities (MedDRA)

  1 month (AEs), 6 months (SAEs)

• Number and proportion of Phase 1 subjects with abnormal hematology, coagulation and blood chemistry lab assessments; number and proportion of Phase 1 subjects with grading shifts in hematology, coagulation and blood chemistry laboratory assessments.

  14 days

• Proportion of subjects achieving antibody responses to specific antigens with results greater than or equal to thresholds specific to each of the 4 antigens in the vaccine based on immunoglobulin-binding and/or opsonophagocytic activity assays.

  1 month

Secondary Outcomes (5)

• Immunoglobulin concentrations for each antigen at each applicable blood sampling time point,

  various, up to 12 months

• Opsonophagocytic activity (OPA) titers at each applicable blood sampling time point,

  1 month

• Immunoglobulin geometric mean fold rise (GMFR) for each antigen

  1 month

• Geometric mean fold rise on opsonophagocytic activity assay titers

  1 month

• Proportion of subjects achieving antibody responses to specific antigens with results greater than or equal to thresholds specific to each of the 4 antigens in the vaccine at at each applicable visit

  various, up to 12 months

Study Arms (4)

1

EXPERIMENTAL

SA4Ag vaccine low dose

Biological: SA4Ag vaccine low dose; Procedure: Blood draw; Procedure: Colonization swab sample

2

EXPERIMENTAL

SA4Ag vaccine mid dose

Biological: SA4Ag vaccine mid dose; Procedure: Blood sample; Procedure: Colonization swab sample

3

EXPERIMENTAL

SA4Ag vaccine high dose

Biological: SA4Ag vaccine high dose; Procedure: Blood draw; Procedure: Colonization swab sample

4

PLACEBO COMPARATOR

Placebo

Biological: Placebo; Procedure: Blood draw; Procedure: Colonization swab sample

Interventions

SA4Ag vaccine low dose BIOLOGICAL

Subjects receive 1 intramuscular injection (0.5 mL) of the low dose level of the SA4Ag vaccine.

1

Blood draw PROCEDURE

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.

1

Colonization swab sample PROCEDURE

Colonization swabs will be collected from all subjects at various time points throughout the study.

1

SA4Ag vaccine mid dose BIOLOGICAL

Subjects receive 1 intramuscular injection (0.5 mL) of the mid dose level of the SA4Ag vaccine.

2

Blood sample PROCEDURE

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.

2

SA4Ag vaccine high dose BIOLOGICAL

Subjects receive 1 intramuscular injection (0.5 mL) of the high dose level of the SA4Ag vaccine.

3

Placebo BIOLOGICAL

Subjects receive one intramuscular injection (0.5 mL) of commercially available normal saline.

4

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy adults aged 18 to \<65 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.
• Availability for the entire duration of the study, and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures including completion of the electronic diary (e-diary) from Day 1 to Day 14 following vaccination(s).
• Ability to be contacted by telephone during study participation.
• All male and female subjects who are biologically capable of having children must agree and commit to the use of a reliable method of birth control for the duration of the study.

You may not qualify if:

• Unstable chronic medical condition or disease requiring significant change in therapy or hospitalization within 3 months before receipt of study vaccine.
• Serious chronic medical disorders and any other disorder that in the investigator's opinion precludes the subject from participating in the study
• Donation of blood volume of 250 mL or greater (excluding protocol-required blood collection), or donation of plasma within 3 months prior to enrollment.
• 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 1 month post-vaccination.
• Any contraindication to vaccination or vaccine components.
• Immunocompromised persons and subjects currently on immunosuppressive therapy or with a history of immunosuppressive therapy, including chemotherapy agents or long term systemic corticosteroids.
• 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.
• Subjects who are investigational site staff members or subjects who are immediate family members (1st 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.
• For Phase 1 subjects only, any abnormality in screening hematology, coagulation and/or blood chemistry laboratory values.
• Women who are pregnant (as determined by urine pregnancy test) or breastfeeding.
• 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.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (16)

Broward Research Group

Hollywood, Florida, 33024, United States

Location

Miami Research Associates

South Miami, Florida, 33143, United States

Location

Vince and Associates Clinical Research

Overland Park, Kansas, 66212, United States

Location

Kentucky Pediatric/Adult Research

Bardstown, Kentucky, 40004, United States

Location

SNBL Clinical Pharmacology Center, Inc.

Baltimore, Maryland, 21201, United States

Location

Prism Research

Saint Paul, Minnesota, 55114, United States

Location

Buffalo Clinical Research Center, LLC

Buffalo, New York, 14202, United States

Location

PMG Research of Raleigh, LLC d/b/a PMG Research of Cary

Cary, North Carolina, 27518, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45206, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

New Orleans Center for Clinical Research

Knoxville, Tennessee, 37920, United States

Location

Volunteer Research Group

Knoxville, Tennessee, 37920, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Benchmark Research

Austin, Texas, 78705, United States

Location

Roberta Braun, M.D.

Austin, Texas, 78705, United States

Location

Texas Center for Drug Development, Inc.

Houston, Texas, 77081, United States

Location

Related Publications (2)

• Creech CB, Frenck RW, Fiquet A, Feldman R, Kankam MK, Pathirana S, Baber J, Radley D, Cooper D, Eiden J, Gruber WC, Jansen KU, Anderson AS, Gurtman A. Persistence of Immune Responses Through 36 Months in Healthy Adults After Vaccination With a Novel Staphylococcus aureus 4-Antigen Vaccine (SA4Ag). Open Forum Infect Dis. 2019 Dec 24;7(1):ofz532. doi: 10.1093/ofid/ofz532. eCollection 2020 Jan.

  PMID: 31993453 DERIVED

• Frenck RW Jr, Creech CB, Sheldon EA, Seiden DJ, Kankam MK, Baber J, Zito E, Hubler R, Eiden J, Severs JM, Sebastian S, Nanra J, Jansen KU, Gruber WC, Anderson AS, Girgenti D. Safety, tolerability, and immunogenicity of a 4-antigen Staphylococcus aureus vaccine (SA4Ag): Results from a first-in-human randomised, placebo-controlled phase 1/2 study. Vaccine. 2017 Jan 5;35(2):375-384. doi: 10.1016/j.vaccine.2016.11.010. Epub 2016 Dec 1.

  PMID: 27916408 DERIVED

MeSH Terms

Conditions

Staphylococcal Infections

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 31, 2011
• First Posted: June 2, 2011
• Study Start: August 1, 2011
• Primary Completion: January 1, 2013
• Study Completion: January 1, 2013
• Last Updated: March 4, 2019

Record last verified: 2019-02

Locations

US (16)