Clinical trial NCT01364571: 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
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) In Healthy Adults Aged 18 To <65 Years
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Staphylococcal Infections
Keywords: Staphylococcus aureus
vaccine
staphylococcal infection
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2011-06-02
Enrollment: 456
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: 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)
timeFrame: 14 days
measure: 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
timeFrame: 14 days
measure: Number and proportion of subjects reporting unsolicited AEs and serious adverse events (SAEs) categorized according to the Medical Dictionary for Regulatory Activities (MedDRA)
timeFrame: 1 month (AEs), 6 months (SAEs)
measure: 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.
timeFrame: 14 days
measure: 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.
timeFrame: 1 month
Secondary outcomes:
measure: Immunoglobulin concentrations for each antigen at each applicable blood sampling time point,
timeFrame: various, up to 12 months
measure: Opsonophagocytic activity (OPA) titers at each applicable blood sampling time point,
timeFrame: 1 month
measure: Immunoglobulin geometric mean fold rise (GMFR) for each antigen
timeFrame: 1 month
measure: Geometric mean fold rise on opsonophagocytic activity assay titers
timeFrame: 1 month
measure: 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
timeFrame: various, up to 12 months
Other outcomes:
Locations:
city: Hollywood
country: United States
facility: Broward Research Group
state: Florida
city: South Miami
country: United States
facility: Miami Research Associates
state: Florida
city: Overland Park
country: United States
facility: Vince and Associates Clinical Research
state: Kansas
city: Bardstown
country: United States
facility: Kentucky Pediatric/Adult Research
state: Kentucky
city: Baltimore
country: United States
facility: SNBL Clinical Pharmacology Center, Inc.
state: Maryland
city: Saint Paul
country: United States
facility: Prism Research
state: Minnesota
city: Buffalo
country: United States
facility: Buffalo Clinical Research Center, LLC
state: New York
city: Cary
country: United States
facility: PMG Research of Raleigh, LLC d/b/a PMG Research of Cary
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Knoxville
country: United States
facility: New Orleans Center for Clinical Research
state: Tennessee
city: Knoxville
country: United States
facility: Volunteer Research Group
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Austin
country: United States
facility: Benchmark Research
state: Texas
city: Austin
country: United States
facility: Roberta Braun, M.D.
state: Texas
city: Houston
country: United States
facility: Texas Center for Drug Development, Inc.
state: Texas
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.