Staphylococcal Vaccine
Conditions
Keywords
Staphylococcal Vaccine, Post-operative Surgical Site Infection, Spinal Surgery, MRSA, Staphylococcus aureus
Brief summary
The purposes of the clinical trial are to determine whether the SA4Ag vaccine can prevent postoperative Staphylococcus aureus infections in patients who are undergoing elective spinal fusion surgery, and to evaluate the safety of SA4Ag in patients who are undergoing elective spinal surgery.
Interventions
BIOLOGICALStaphylococcus aureus 4-Antigen (SA4Ag) Vaccine
SA4Ag vaccine reconstituted in 0.5mL water for injection. Administered via IM injection, once 10 to 60 days prior to surgery
OTHERPlacebo
Vaccine excipients reconstituted in 0.5mL water for injections. Administered via IM injection given 10 to 60 days prior to surgery
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Subject must be scheduled to undergo an elective open posterior spinal fusion procedures with multilevel instrumentation, 10 to 60 days after study vaccination. * Subject must be available 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 for 10 days after study vaccination. * Aged 18 to \<86 years old
Exclusion criteria
* Planned spinal fusion procedure requiring separate operations performed on separate days (ie, staged procedure). * Surgical indication of malignancy, infection or acute or emergency trauma. * History of major surgery within 3 months prior to enrollment, or anticipated major surgery other than the Index Surgical Procedure between study enrollment and completion of study participation. * History of any spinal surgery performed within 6 months prior to study enrollment. * History of any previous spinal surgery resulting in postoperative BSI or SSI. * Congenital or acquired immunodeficiency disorder, rheumatologic disorder or other illness requiring chronic treatment with known immunosuppressant medications, including monoclonal antibodies within a year of enrollment or the use of systemic corticosteroids for \> 14 days within 30 days prior to enrollment. * History of leukemia, lymphoma, underlying bone marrow disorder or history of bone marrow transplant.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Serious Adverse Events (SAEs) From The Day of Surgery (Day 1) Until Last Postoperative Evaluation on Day 180 | Day of surgery (Day 1) up to Day 180 after surgery | An AE was any untoward medical occurrence in a participant who received study vaccine without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death, initial or prolonged inpatient hospitalization, life-threatening experience (immediate risk of dying), persistent or significant disability/incapacity, congenital anomaly. |
| Number of Participants With Newly Diagnosed Chronic Medical Disorders From First Postoperative Evaluation on Day 42 Until Last Postoperative Evaluation on Day 180 | Day 42 up to Day 180 (up to 138 days) | A newly diagnosed chronic medical disorder was defined as a disease or medical condition, not previously identified, that was expected to be persistent or otherwise long-lasting in its effects. |
| Number of Participants With Serious Adverse Events (SAEs) From Vaccination Until Last Postoperative Evaluation on Day 180 | From vaccination up to Day 180 after surgery (190-240 days after vaccination) | An AE was any untoward medical occurrence in a participant who received study vaccine without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death, initial or prolonged inpatient hospitalization, life-threatening experience (immediate risk of dying), persistent or significant disability/incapacity, congenital anomaly. |
| Number of Participants With Serious Adverse Events (SAEs) From Vaccination Until Day of Surgery (Day 1) | From vaccination up to Day of surgery (Day 1) (10-60 days after vaccination) | An AE was any untoward medical occurrence in a participant who received study vaccine without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death, initial or prolonged inpatient hospitalization, life-threatening experience (immediate risk of dying), persistent or significant disability/incapacity, congenital anomaly. |
| Number of Participants With Postoperative Staphylococcus (S.) Aureus Bloodstream Infection (BSI) And/or Surgical-site Infection (SSI-Including Deep Incisional or Organ/Space) Occurred Within 90 Days After Spinal Surgery | Day of surgery (Day 1) up to Day 90 | BSI: clinical infection involved a recognized pathogen (S. aureus) cultured from 1 or more blood cultures or a commensal organism cultured from 2 or more blood cultures whether primary or secondary to infection at another site. SSI: infection at a surgical incision. Types of SSI in this outcome measure: Deep incisional SSI: infection involved deep soft tissues of incision (example \[e.g.\] fascial and muscle layers), Organ/space SSI: infection involved any part of body excluding skin incision, fascia or muscle layers, that was opened or manipulated during operative procedure. Overall number of participants with postoperative BSI and/or SSI (including deep incisional or organ/space), caused by S. aureus, occurred within 90 days of post elective open posterior spinal fusion surgery with multilevel instrumentation, as confirmed by event adjudication committee (EAC) have been reported. A participant may have met criteria for both BSI and SSI (deep incisional or organ/space). |
| Percentage of Participants With Local Reactions Within 10 Days After Vaccination | Within 10 days after Vaccination | Local reactions were recorded using an electronic diary (e-diary). Local reactions included redness, swelling and pain at the injection site. Redness and swelling were categorized as mild (2.5 to 5.0 centimeters \[cm\]), moderate (5.5 to 10.0 cm) and, severe (greater than or equal to \[\>=\] 10.5 cm). Pain at the injection site was defined as mild (did not interfere with activity), moderate (interfered with activity), and severe (prevented daily activity). Participants may be represented in more than 1 row. Here, Any for redness, swelling, pain at the injection site represents any grade of these local reactions among mild, moderate or severe. |
| Percentage of Participants With Systemic Reactions Within 10 Days After Vaccination | Within 10 days after Vaccination | Systemic reactions included fever, fatigue, headache, diarrhea, vomiting, muscle pain and joint pain, were recorded using an e-diary. Fever was graded as 38.0 to 38.4 degree Celsius (C), 38.5 to 38.9 degree C, 39.0 to 40.0 degree C and greater than (\>) 40.0 degree C. Vomiting was graded as mild (1-2 times in 24 hours), moderate (\>2 times in 24 hours) and severe (required intravenous hydration). Diarrhea was graded as mild (2-3 loose stools in 24 hours), moderate (4-5 loose stools in 24 hours) and severe (\>=6 loose stools in 24 hours). Headache, fatigue, muscle pain and joint pain were graded as mild (no interference with activity), moderate (some interference with activity) and severe (prevented daily routine activity). Participants may be represented in more than 1 row. Here any for fever, fatigue, headache, vomiting, diarrhea, muscle pain, joint pain represents any grade of these systemic reactions among mild, moderate or severe. |
| Number of Participants With Adverse Events (AEs) From Vaccination Until The Day of Surgery (Day 1) | From vaccination up to Day of surgery (Day 1) (10-60 days after vaccination) | An adverse event (AE) was any untoward medical occurrence in a participant who received study vaccine without regard to possibility of causal relationship. AEs including serious as well non-serious AEs. |
| Number of Participants With Adverse Events (AEs) From Vaccination Until First Postoperative Evaluation on Day 42 | From vaccination until Day 42 after surgery (52-102 days after vaccination) | An AE was any untoward medical occurrence in a participant who received study vaccine without regard to possibility of causal relationship. AEs including serious as well non-serious AEs. |
| Number of Participants With Adverse Events (AEs) From The Day of Surgery (Day 1) Until First Postoperative Evaluation on Day 42 | Day of surgery (Day 1) up to Day 42 after surgery | An AE was any untoward medical occurrence in a participant who received study vaccine without regard to possibility of causal relationship. AEs including serious as well non-serious AEs. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Any Postoperative S. Aureus Surgical-site Infection (SSI-Superficial, Deep Incisional or Organ/Space) Occurred Within 90 Days After Surgery | Day of surgery (Day 1) up to Day 90 after surgery | SSI: infection at a surgical incision. Types of SSI in this outcome measure: Superficial SSI: Infection involved only skin and subcutaneous tissue of the incision, Deep incisional SSI: infection involved deep soft tissues of incision (e.g. fascial and muscle layers), Organ/space SSI: infection involved any part of body, excluding skin incision, fascia, or muscle layers, that was opened or manipulated during operative procedure. Overall number of participants with postoperative SSI (including superficial, deep incisional and/or organ/space SSI) caused by S. aureus, occurred within 90 days after elective open posterior spinal fusion surgery with multilevel instrumentation as confirmed by EAC have been reported. |
| Number of Participants With Any Postoperative S. Aureus Surgical-site Infection (SSI-Superficial, Deep Incisional or Organ/Space) Occurred Within 180 Days After Surgery | Day of surgery (Day 1) up to Day 180 after surgery | SSI: infection at a surgical incision. Types of SSI in this outcome measure: Superficial SSI: Infection involved only skin and subcutaneous tissue of the incision, Deep incisional SSI: infection involved deep soft tissues of incision (e.g. fascial and muscle layers), Organ/space SSI: infection involved any part of body, excluding skin incision, fascia, or muscle layers, that was opened or manipulated during operative procedure. Overall number of participants with postoperative SSI (including superficial, deep incisional and/or organ/space SSI) caused by S. aureus, occurred within 180 days after elective open posterior spinal fusion surgery with multilevel instrumentation as confirmed by EAC have been reported. |
| Number of Participants With Postoperative S. Aureus Blood Stream Infection (BSI) And/or Surgical-site Infection (SSI-Including Deep Incisional or Organ/Space) Occurred Within 180 Days After Surgery | Day of surgery (Day 1) up to Day 180 after surgery | BSI: clinical infection involved a recognized pathogen (S. aureus) cultured from 1 or more blood cultures or a commensal organism cultured from 2 or more blood cultures whether primary or secondary to infection at another site. SSI: infection at a surgical incision. Types of SSI in this outcome measure: Deep incisional SSI: infection involved deep soft tissues of incision (e.g. fascial and muscle layers), Organ/space SSI: infection involved any part of body excluding skin incision, fascia or muscle layers, that was opened or manipulated during operative procedure. Overall number of participants with postoperative BSI and/or SSI (including deep incisional or organ/space), caused by S. aureus, occurred within 180 days of post elective open posterior spinal fusion surgery with multilevel instrumentation, as confirmed by EAC have been reported. A participant may have met criteria for both BSI and SSI (deep incisional or organ/space). |
Countries
Austria, Bulgaria, Canada, France, Germany, Hungary, Japan, Spain, Sweden, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Staphylococcus Aureus 4-antigen (SA4Ag) Participants randomized to SA4Ag received a single dose of 0.5 mL SA4Ag vaccine intramuscularly, 10 to 60 days prior to their scheduled surgery. Participants were followed from vaccination up to 6 months after their spinal surgical procedure. | 1,708 |
| Placebo Participants randomized to this arm received placebo containing the vaccine excipients reconstituted in 0.5mL water for injection. It was administered via intramuscular injection, 10 to 60 days prior to scheduled surgery. Participants were followed from vaccination up to 6 months after their spinal surgical procedure. | 1,709 |
| Total | 3,417 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 5 |
| Overall Study | Death | 13 | 10 |
| Overall Study | Did not meet entrance criteria | 5 | 2 |
| Overall Study | Lost to Follow-up | 19 | 20 |
| Overall Study | No longer meet eligibility criteria | 40 | 43 |
| Overall Study | Other | 11 | 13 |
| Overall Study | Study terminated by sponsor | 5 | 5 |
| Overall Study | Withdrawal of consent | 31 | 32 |
Baseline characteristics
| Characteristic | Placebo | Total | Staphylococcus Aureus 4-antigen (SA4Ag) |
|---|---|---|---|
| Age, Continuous | 62.6 Years STANDARD_DEVIATION 12.6 | 62.7 Years STANDARD_DEVIATION 12.4 | 62.7 Years STANDARD_DEVIATION 12.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 69 Participants | 138 Participants | 69 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1639 Participants | 3273 Participants | 1634 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 6 Participants | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 290 Participants | 585 Participants | 295 Participants |
| Race (NIH/OMB) Black or African American | 111 Participants | 201 Participants | 90 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 25 Participants | 53 Participants | 28 Participants |
| Race (NIH/OMB) White | 1283 Participants | 2578 Participants | 1295 Participants |
| Sex: Female, Male Female | 940 Participants | 1890 Participants | 950 Participants |
| Sex: Female, Male Male | 769 Participants | 1527 Participants | 758 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 13 / 1,708 | 10 / 1,709 |
| other Total, other adverse events | 1,530 / 1,708 | 1,489 / 1,709 |
| serious Total, serious adverse events | 403 / 1,708 | 424 / 1,709 |
Outcome results
Primary
Number of Participants With Adverse Events (AEs) From The Day of Surgery (Day 1) Until First Postoperative Evaluation on Day 42
An AE was any untoward medical occurrence in a participant who received study vaccine without regard to possibility of causal relationship. AEs including serious as well non-serious AEs.
Time frame: Day of surgery (Day 1) up to Day 42 after surgery
Population: Safety population: all participants who received investigational product in this study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Staphylococcus Aureus 4-antigen (SA4Ag) | Number of Participants With Adverse Events (AEs) From The Day of Surgery (Day 1) Until First Postoperative Evaluation on Day 42 | 1136 Participants |
| Placebo | Number of Participants With Adverse Events (AEs) From The Day of Surgery (Day 1) Until First Postoperative Evaluation on Day 42 | 1167 Participants |
Primary
Number of Participants With Adverse Events (AEs) From Vaccination Until First Postoperative Evaluation on Day 42
An AE was any untoward medical occurrence in a participant who received study vaccine without regard to possibility of causal relationship. AEs including serious as well non-serious AEs.
Time frame: From vaccination until Day 42 after surgery (52-102 days after vaccination)
Population: Safety population: all participants who received investigational product in this study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Staphylococcus Aureus 4-antigen (SA4Ag) | Number of Participants With Adverse Events (AEs) From Vaccination Until First Postoperative Evaluation on Day 42 | 1198 Participants |
| Placebo | Number of Participants With Adverse Events (AEs) From Vaccination Until First Postoperative Evaluation on Day 42 | 1213 Participants |
Primary
Number of Participants With Adverse Events (AEs) From Vaccination Until The Day of Surgery (Day 1)
An adverse event (AE) was any untoward medical occurrence in a participant who received study vaccine without regard to possibility of causal relationship. AEs including serious as well non-serious AEs.
Time frame: From vaccination up to Day of surgery (Day 1) (10-60 days after vaccination)
Population: Safety population: all participants who received investigational product in this study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Staphylococcus Aureus 4-antigen (SA4Ag) | Number of Participants With Adverse Events (AEs) From Vaccination Until The Day of Surgery (Day 1) | 213 Participants |
| Placebo | Number of Participants With Adverse Events (AEs) From Vaccination Until The Day of Surgery (Day 1) | 178 Participants |
Primary
Number of Participants With Newly Diagnosed Chronic Medical Disorders From First Postoperative Evaluation on Day 42 Until Last Postoperative Evaluation on Day 180
A newly diagnosed chronic medical disorder was defined as a disease or medical condition, not previously identified, that was expected to be persistent or otherwise long-lasting in its effects.
Time frame: Day 42 up to Day 180 (up to 138 days)
Population: Safety population: all participants who received investigational product in this study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Staphylococcus Aureus 4-antigen (SA4Ag) | Number of Participants With Newly Diagnosed Chronic Medical Disorders From First Postoperative Evaluation on Day 42 Until Last Postoperative Evaluation on Day 180 | 29 Participants |
| Placebo | Number of Participants With Newly Diagnosed Chronic Medical Disorders From First Postoperative Evaluation on Day 42 Until Last Postoperative Evaluation on Day 180 | 41 Participants |
Primary
Number of Participants With Postoperative Staphylococcus (S.) Aureus Bloodstream Infection (BSI) And/or Surgical-site Infection (SSI-Including Deep Incisional or Organ/Space) Occurred Within 90 Days After Spinal Surgery
BSI: clinical infection involved a recognized pathogen (S. aureus) cultured from 1 or more blood cultures or a commensal organism cultured from 2 or more blood cultures whether primary or secondary to infection at another site. SSI: infection at a surgical incision. Types of SSI in this outcome measure: Deep incisional SSI: infection involved deep soft tissues of incision (example \[e.g.\] fascial and muscle layers), Organ/space SSI: infection involved any part of body excluding skin incision, fascia or muscle layers, that was opened or manipulated during operative procedure. Overall number of participants with postoperative BSI and/or SSI (including deep incisional or organ/space), caused by S. aureus, occurred within 90 days of post elective open posterior spinal fusion surgery with multilevel instrumentation, as confirmed by event adjudication committee (EAC) have been reported. A participant may have met criteria for both BSI and SSI (deep incisional or organ/space).
Time frame: Day of surgery (Day 1) up to Day 90
Population: Per-protocol (PP) efficacy population: all eligible participants, vaccinated as randomized, who underwent surgery per study-defined criteria within 9-90 days (inclusive) post vaccination (expanded from 10-60 days window in protocol), had no infection/malignancy at surgery and had no major protocol violation prior to reporting S. aureus infection.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Staphylococcus Aureus 4-antigen (SA4Ag) | Number of Participants With Postoperative Staphylococcus (S.) Aureus Bloodstream Infection (BSI) And/or Surgical-site Infection (SSI-Including Deep Incisional or Organ/Space) Occurred Within 90 Days After Spinal Surgery | 14 Participants |
| Placebo | Number of Participants With Postoperative Staphylococcus (S.) Aureus Bloodstream Infection (BSI) And/or Surgical-site Infection (SSI-Including Deep Incisional or Organ/Space) Occurred Within 90 Days After Spinal Surgery | 14 Participants |
95% CI: [-126.3, 55.81]
Primary
Number of Participants With Serious Adverse Events (SAEs) From The Day of Surgery (Day 1) Until Last Postoperative Evaluation on Day 180
An AE was any untoward medical occurrence in a participant who received study vaccine without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death, initial or prolonged inpatient hospitalization, life-threatening experience (immediate risk of dying), persistent or significant disability/incapacity, congenital anomaly.
Time frame: Day of surgery (Day 1) up to Day 180 after surgery
Population: Safety population: all participants who received investigational product in this study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Staphylococcus Aureus 4-antigen (SA4Ag) | Number of Participants With Serious Adverse Events (SAEs) From The Day of Surgery (Day 1) Until Last Postoperative Evaluation on Day 180 | 384 Participants |
| Placebo | Number of Participants With Serious Adverse Events (SAEs) From The Day of Surgery (Day 1) Until Last Postoperative Evaluation on Day 180 | 401 Participants |
Primary
Number of Participants With Serious Adverse Events (SAEs) From Vaccination Until Day of Surgery (Day 1)
An AE was any untoward medical occurrence in a participant who received study vaccine without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death, initial or prolonged inpatient hospitalization, life-threatening experience (immediate risk of dying), persistent or significant disability/incapacity, congenital anomaly.
Time frame: From vaccination up to Day of surgery (Day 1) (10-60 days after vaccination)
Population: Safety population: all participants who received investigational product in this study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Staphylococcus Aureus 4-antigen (SA4Ag) | Number of Participants With Serious Adverse Events (SAEs) From Vaccination Until Day of Surgery (Day 1) | 27 Participants |
| Placebo | Number of Participants With Serious Adverse Events (SAEs) From Vaccination Until Day of Surgery (Day 1) | 26 Participants |
Primary
Number of Participants With Serious Adverse Events (SAEs) From Vaccination Until Last Postoperative Evaluation on Day 180
An AE was any untoward medical occurrence in a participant who received study vaccine without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death, initial or prolonged inpatient hospitalization, life-threatening experience (immediate risk of dying), persistent or significant disability/incapacity, congenital anomaly.
Time frame: From vaccination up to Day 180 after surgery (190-240 days after vaccination)
Population: Safety population: all participants who received investigational product in this study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Staphylococcus Aureus 4-antigen (SA4Ag) | Number of Participants With Serious Adverse Events (SAEs) From Vaccination Until Last Postoperative Evaluation on Day 180 | 403 Participants |
| Placebo | Number of Participants With Serious Adverse Events (SAEs) From Vaccination Until Last Postoperative Evaluation on Day 180 | 424 Participants |
Primary
Percentage of Participants With Local Reactions Within 10 Days After Vaccination
Local reactions were recorded using an electronic diary (e-diary). Local reactions included redness, swelling and pain at the injection site. Redness and swelling were categorized as mild (2.5 to 5.0 centimeters \[cm\]), moderate (5.5 to 10.0 cm) and, severe (greater than or equal to \[\>=\] 10.5 cm). Pain at the injection site was defined as mild (did not interfere with activity), moderate (interfered with activity), and severe (prevented daily activity). Participants may be represented in more than 1 row. Here, Any for redness, swelling, pain at the injection site represents any grade of these local reactions among mild, moderate or severe.
Time frame: Within 10 days after Vaccination
Population: Safety population: all participants who received investigational product in this study. Here, Overall Number of Participants Analyzed, N signifies number of participants analyzed for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Staphylococcus Aureus 4-antigen (SA4Ag) | Percentage of Participants With Local Reactions Within 10 Days After Vaccination | Redness: Mild | 5.3 Percentage of participants |
| Staphylococcus Aureus 4-antigen (SA4Ag) | Percentage of Participants With Local Reactions Within 10 Days After Vaccination | Redness: Moderate | 3.1 Percentage of participants |
| Staphylococcus Aureus 4-antigen (SA4Ag) | Percentage of Participants With Local Reactions Within 10 Days After Vaccination | Redness: Severe | 0.8 Percentage of participants |
| Staphylococcus Aureus 4-antigen (SA4Ag) | Percentage of Participants With Local Reactions Within 10 Days After Vaccination | Swelling: Any | 8.0 Percentage of participants |
| Staphylococcus Aureus 4-antigen (SA4Ag) | Percentage of Participants With Local Reactions Within 10 Days After Vaccination | Swelling: Mild | 4.6 Percentage of participants |
| Staphylococcus Aureus 4-antigen (SA4Ag) | Percentage of Participants With Local Reactions Within 10 Days After Vaccination | Swelling: Moderate | 2.7 Percentage of participants |
| Staphylococcus Aureus 4-antigen (SA4Ag) | Percentage of Participants With Local Reactions Within 10 Days After Vaccination | Swelling: Severe | 0.7 Percentage of participants |
| Staphylococcus Aureus 4-antigen (SA4Ag) | Percentage of Participants With Local Reactions Within 10 Days After Vaccination | Pain at the injection site: Any | 24.1 Percentage of participants |
| Staphylococcus Aureus 4-antigen (SA4Ag) | Percentage of Participants With Local Reactions Within 10 Days After Vaccination | Pain at the injection site: Mild | 19.2 Percentage of participants |
| Staphylococcus Aureus 4-antigen (SA4Ag) | Percentage of Participants With Local Reactions Within 10 Days After Vaccination | Pain at the injection site: Moderate | 4.3 Percentage of participants |
| Staphylococcus Aureus 4-antigen (SA4Ag) | Percentage of Participants With Local Reactions Within 10 Days After Vaccination | Pain at the injection site: Severe | 0.6 Percentage of participants |
| Staphylococcus Aureus 4-antigen (SA4Ag) | Percentage of Participants With Local Reactions Within 10 Days After Vaccination | Redness: Any | 9.2 Percentage of participants |
| Placebo | Percentage of Participants With Local Reactions Within 10 Days After Vaccination | Pain at the injection site: Moderate | 1.3 Percentage of participants |
| Placebo | Percentage of Participants With Local Reactions Within 10 Days After Vaccination | Redness: Mild | 0.9 Percentage of participants |
| Placebo | Percentage of Participants With Local Reactions Within 10 Days After Vaccination | Redness: Any | 0.9 Percentage of participants |
| Placebo | Percentage of Participants With Local Reactions Within 10 Days After Vaccination | Redness: Moderate | 0.1 Percentage of participants |
| Placebo | Percentage of Participants With Local Reactions Within 10 Days After Vaccination | Pain at the injection site: Any | 8.4 Percentage of participants |
| Placebo | Percentage of Participants With Local Reactions Within 10 Days After Vaccination | Redness: Severe | 0.0 Percentage of participants |
| Placebo | Percentage of Participants With Local Reactions Within 10 Days After Vaccination | Pain at the injection site: Severe | 0.1 Percentage of participants |
| Placebo | Percentage of Participants With Local Reactions Within 10 Days After Vaccination | Swelling: Any | 1.0 Percentage of participants |
| Placebo | Percentage of Participants With Local Reactions Within 10 Days After Vaccination | Pain at the injection site: Mild | 7.0 Percentage of participants |
| Placebo | Percentage of Participants With Local Reactions Within 10 Days After Vaccination | Swelling: Severe | 0.0 Percentage of participants |
| Placebo | Percentage of Participants With Local Reactions Within 10 Days After Vaccination | Swelling: Mild | 0.7 Percentage of participants |
| Placebo | Percentage of Participants With Local Reactions Within 10 Days After Vaccination | Swelling: Moderate | 0.3 Percentage of participants |
Comparison: Redness: Anyp-value: <0.00195% CI: [6.9, 9.8]Miettinen and Nurminen
Comparison: Redness: Mild95% CI: [3.3, 5.6]
Comparison: Redness: Moderate95% CI: [2.3, 4]
Comparison: Redness: Severe95% CI: [0.5, 1.4]
Comparison: Swelling: Anyp-value: <0.00195% CI: [5.7, 8.4]Miettinen and Nurminen
Comparison: Swelling: Mild95% CI: [2.8, 5]
Comparison: Swelling: Moderate95% CI: [1.7, 3.3]
Comparison: Swelling: Severe95% CI: [0.4, 1.2]
Comparison: Pain at the injection site: Anyp-value: <0.00195% CI: [13.3, 18.1]Miettinen and Nurminen
Comparison: Pain at the injection site: Mild95% CI: [10, 14.5]
Comparison: Pain at the injection site: Moderate95% CI: [1.9, 4.2]
Comparison: Pain at the injection site: Severe95% CI: [0.1, 1]
Primary
Percentage of Participants With Systemic Reactions Within 10 Days After Vaccination
Systemic reactions included fever, fatigue, headache, diarrhea, vomiting, muscle pain and joint pain, were recorded using an e-diary. Fever was graded as 38.0 to 38.4 degree Celsius (C), 38.5 to 38.9 degree C, 39.0 to 40.0 degree C and greater than (\>) 40.0 degree C. Vomiting was graded as mild (1-2 times in 24 hours), moderate (\>2 times in 24 hours) and severe (required intravenous hydration). Diarrhea was graded as mild (2-3 loose stools in 24 hours), moderate (4-5 loose stools in 24 hours) and severe (\>=6 loose stools in 24 hours). Headache, fatigue, muscle pain and joint pain were graded as mild (no interference with activity), moderate (some interference with activity) and severe (prevented daily routine activity). Participants may be represented in more than 1 row. Here any for fever, fatigue, headache, vomiting, diarrhea, muscle pain, joint pain represents any grade of these systemic reactions among mild, moderate or severe.
Time frame: Within 10 days after Vaccination
Population: Safety population: all participants who received investigational product in this study. Here, Overall Number of Participants Analyzed signifies number of participants analyzed for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Staphylococcus Aureus 4-antigen (SA4Ag) | Percentage of Participants With Systemic Reactions Within 10 Days After Vaccination | Fever: Any | 2.0 Percentage of participants |
| Staphylococcus Aureus 4-antigen (SA4Ag) | Percentage of Participants With Systemic Reactions Within 10 Days After Vaccination | Fever: >40.0 degree C | 0.1 Percentage of participants |
| Staphylococcus Aureus 4-antigen (SA4Ag) | Percentage of Participants With Systemic Reactions Within 10 Days After Vaccination | Headache: Any | 32.4 Percentage of participants |
| Staphylococcus Aureus 4-antigen (SA4Ag) | Percentage of Participants With Systemic Reactions Within 10 Days After Vaccination | Headache: Mild | 17.7 Percentage of participants |
| Staphylococcus Aureus 4-antigen (SA4Ag) | Percentage of Participants With Systemic Reactions Within 10 Days After Vaccination | Fever: 38.5 degree C to 38.9 degree C | 0.5 Percentage of participants |
| Staphylococcus Aureus 4-antigen (SA4Ag) | Percentage of Participants With Systemic Reactions Within 10 Days After Vaccination | Headache: Moderate | 13.5 Percentage of participants |
| Staphylococcus Aureus 4-antigen (SA4Ag) | Percentage of Participants With Systemic Reactions Within 10 Days After Vaccination | Fatigue: Any | 43.3 Percentage of participants |
| Staphylococcus Aureus 4-antigen (SA4Ag) | Percentage of Participants With Systemic Reactions Within 10 Days After Vaccination | Headache: Severe | 1.2 Percentage of participants |
| Staphylococcus Aureus 4-antigen (SA4Ag) | Percentage of Participants With Systemic Reactions Within 10 Days After Vaccination | Diarrhea: Mild | 13.0 Percentage of participants |
| Staphylococcus Aureus 4-antigen (SA4Ag) | Percentage of Participants With Systemic Reactions Within 10 Days After Vaccination | Diarrhea: Any | 17.0 Percentage of participants |
| Staphylococcus Aureus 4-antigen (SA4Ag) | Percentage of Participants With Systemic Reactions Within 10 Days After Vaccination | Diarrhea: Moderate | 3.4 Percentage of participants |
| Staphylococcus Aureus 4-antigen (SA4Ag) | Percentage of Participants With Systemic Reactions Within 10 Days After Vaccination | Fever: 39.0 degree C to 40.0 degree C | 0.2 Percentage of participants |
| Staphylococcus Aureus 4-antigen (SA4Ag) | Percentage of Participants With Systemic Reactions Within 10 Days After Vaccination | Diarrhea: Severe | 0.5 Percentage of participants |
| Staphylococcus Aureus 4-antigen (SA4Ag) | Percentage of Participants With Systemic Reactions Within 10 Days After Vaccination | Vomiting: Moderate | 0.3 Percentage of participants |
| Staphylococcus Aureus 4-antigen (SA4Ag) | Percentage of Participants With Systemic Reactions Within 10 Days After Vaccination | Vomiting: Any | 2.7 Percentage of participants |
| Staphylococcus Aureus 4-antigen (SA4Ag) | Percentage of Participants With Systemic Reactions Within 10 Days After Vaccination | Fatigue: Mild | 14.0 Percentage of participants |
| Staphylococcus Aureus 4-antigen (SA4Ag) | Percentage of Participants With Systemic Reactions Within 10 Days After Vaccination | Vomiting: Mild | 2.4 Percentage of participants |
| Staphylococcus Aureus 4-antigen (SA4Ag) | Percentage of Participants With Systemic Reactions Within 10 Days After Vaccination | Vomiting: Severe | 0.0 Percentage of participants |
| Staphylococcus Aureus 4-antigen (SA4Ag) | Percentage of Participants With Systemic Reactions Within 10 Days After Vaccination | Fever: 38.0 degree C to 38.4 degree C | 1.3 Percentage of participants |
| Staphylococcus Aureus 4-antigen (SA4Ag) | Percentage of Participants With Systemic Reactions Within 10 Days After Vaccination | Muscle pain: Mild | 10.1 Percentage of participants |
| Staphylococcus Aureus 4-antigen (SA4Ag) | Percentage of Participants With Systemic Reactions Within 10 Days After Vaccination | Muscle pain: Any | 27.9 Percentage of participants |
| Staphylococcus Aureus 4-antigen (SA4Ag) | Percentage of Participants With Systemic Reactions Within 10 Days After Vaccination | Muscle pain: Moderate | 15.7 Percentage of participants |
| Staphylococcus Aureus 4-antigen (SA4Ag) | Percentage of Participants With Systemic Reactions Within 10 Days After Vaccination | Muscle pain: Severe | 2.1 Percentage of participants |
| Staphylococcus Aureus 4-antigen (SA4Ag) | Percentage of Participants With Systemic Reactions Within 10 Days After Vaccination | Fatigue: Moderate | 24.9 Percentage of participants |
| Staphylococcus Aureus 4-antigen (SA4Ag) | Percentage of Participants With Systemic Reactions Within 10 Days After Vaccination | Joint pain: Any | 27.5 Percentage of participants |
| Staphylococcus Aureus 4-antigen (SA4Ag) | Percentage of Participants With Systemic Reactions Within 10 Days After Vaccination | Joint pain: Moderate | 16.1 Percentage of participants |
| Staphylococcus Aureus 4-antigen (SA4Ag) | Percentage of Participants With Systemic Reactions Within 10 Days After Vaccination | Joint pain: Mild | 9.6 Percentage of participants |
| Staphylococcus Aureus 4-antigen (SA4Ag) | Percentage of Participants With Systemic Reactions Within 10 Days After Vaccination | Fatigue: Severe | 4.4 Percentage of participants |
| Staphylococcus Aureus 4-antigen (SA4Ag) | Percentage of Participants With Systemic Reactions Within 10 Days After Vaccination | Joint pain: Severe | 1.8 Percentage of participants |
| Placebo | Percentage of Participants With Systemic Reactions Within 10 Days After Vaccination | Diarrhea: Any | 16.0 Percentage of participants |
| Placebo | Percentage of Participants With Systemic Reactions Within 10 Days After Vaccination | Fever: 38.0 degree C to 38.4 degree C | 0.9 Percentage of participants |
| Placebo | Percentage of Participants With Systemic Reactions Within 10 Days After Vaccination | Fever: 39.0 degree C to 40.0 degree C | 0.1 Percentage of participants |
| Placebo | Percentage of Participants With Systemic Reactions Within 10 Days After Vaccination | Fever: >40.0 degree C | 0.0 Percentage of participants |
| Placebo | Percentage of Participants With Systemic Reactions Within 10 Days After Vaccination | Fatigue: Any | 40.4 Percentage of participants |
| Placebo | Percentage of Participants With Systemic Reactions Within 10 Days After Vaccination | Fatigue: Mild | 12.6 Percentage of participants |
| Placebo | Percentage of Participants With Systemic Reactions Within 10 Days After Vaccination | Fatigue: Severe | 4.2 Percentage of participants |
| Placebo | Percentage of Participants With Systemic Reactions Within 10 Days After Vaccination | Headache: Any | 31.2 Percentage of participants |
| Placebo | Percentage of Participants With Systemic Reactions Within 10 Days After Vaccination | Headache: Moderate | 12.0 Percentage of participants |
| Placebo | Percentage of Participants With Systemic Reactions Within 10 Days After Vaccination | Vomiting: Mild | 2.6 Percentage of participants |
| Placebo | Percentage of Participants With Systemic Reactions Within 10 Days After Vaccination | Vomiting: Moderate | 0.7 Percentage of participants |
| Placebo | Percentage of Participants With Systemic Reactions Within 10 Days After Vaccination | Vomiting: Severe | 0.0 Percentage of participants |
| Placebo | Percentage of Participants With Systemic Reactions Within 10 Days After Vaccination | Joint pain: Mild | 8.0 Percentage of participants |
| Placebo | Percentage of Participants With Systemic Reactions Within 10 Days After Vaccination | Joint pain: Severe | 1.7 Percentage of participants |
| Placebo | Percentage of Participants With Systemic Reactions Within 10 Days After Vaccination | Fever: 38.5 degree C to 38.9 degree C | 0.4 Percentage of participants |
| Placebo | Percentage of Participants With Systemic Reactions Within 10 Days After Vaccination | Fatigue: Moderate | 23.6 Percentage of participants |
| Placebo | Percentage of Participants With Systemic Reactions Within 10 Days After Vaccination | Headache: Mild | 18.0 Percentage of participants |
| Placebo | Percentage of Participants With Systemic Reactions Within 10 Days After Vaccination | Headache: Severe | 1.2 Percentage of participants |
| Placebo | Percentage of Participants With Systemic Reactions Within 10 Days After Vaccination | Fever: Any | 1.4 Percentage of participants |
| Placebo | Percentage of Participants With Systemic Reactions Within 10 Days After Vaccination | Diarrhea: Mild | 12.2 Percentage of participants |
| Placebo | Percentage of Participants With Systemic Reactions Within 10 Days After Vaccination | Diarrhea: Moderate | 2.9 Percentage of participants |
| Placebo | Percentage of Participants With Systemic Reactions Within 10 Days After Vaccination | Diarrhea: Severe | 0.9 Percentage of participants |
| Placebo | Percentage of Participants With Systemic Reactions Within 10 Days After Vaccination | Vomiting: Any | 3.3 Percentage of participants |
| Placebo | Percentage of Participants With Systemic Reactions Within 10 Days After Vaccination | Muscle pain: Any | 26.2 Percentage of participants |
| Placebo | Percentage of Participants With Systemic Reactions Within 10 Days After Vaccination | Muscle pain: Mild | 9.3 Percentage of participants |
| Placebo | Percentage of Participants With Systemic Reactions Within 10 Days After Vaccination | Muscle pain: Moderate | 14.6 Percentage of participants |
| Placebo | Percentage of Participants With Systemic Reactions Within 10 Days After Vaccination | Muscle pain: Severe | 2.3 Percentage of participants |
| Placebo | Percentage of Participants With Systemic Reactions Within 10 Days After Vaccination | Joint pain: Any | 25.8 Percentage of participants |
| Placebo | Percentage of Participants With Systemic Reactions Within 10 Days After Vaccination | Joint pain: Moderate | 16.1 Percentage of participants |
Comparison: Fever: Anyp-value: 0.14695% CI: [-0.2, 1.6]Miettinen and Nurminen
Comparison: Fever: 38.0 degree C to 38.4 degree C95% CI: [-0.3, 1.2]
Comparison: Fever: 38.5 degree C to 38.9 degree C95% CI: [-0.4, 0.6]
Comparison: Fever: 39.0 degree C to 40.0 degree C95% CI: [-0.2, 0.5]
Comparison: Fever: \>40.0 degree C95% CI: [-0.2, 0.3]
Comparison: Fatigue: Anyp-value: 0.09395% CI: [-0.5, 6.2]Miettinen and Nurminen
Comparison: Fatigue: Mild95% CI: [-0.9, 3.7]
Comparison: Fatigue: Moderate95% CI: [-1.6, 4.2]
Comparison: Fatigue: Severe95% CI: [-1.2, 1.6]
Comparison: Headache: Anyp-value: 0.44395% CI: [-1.9, 4.4]Miettinen and Nurminen
Comparison: Headache: Mild95% CI: [-2.9, 2.3]
Comparison: Headache: Moderate95% CI: [-0.7, 3.8]
Comparison: Headache: Severe95% CI: [-0.8, 0.8]
Comparison: Diarrhea: Anyp-value: 0.46295% CI: [-1.6, 3.4]Miettinen and Nurminen
Comparison: Diarrhea: Mild95% CI: [-1.5, 3]
Comparison: Diarrhea: Moderate95% CI: [-0.7, 1.7]
Comparison: Diarrhea: Severe95% CI: [-1, 0.2]
Comparison: Vomiting: Anyp-value: 0.395% CI: [-1.8, 0.5]Miettinen and Nurminen
Comparison: Vomiting: Mild95% CI: [-1.3, 0.8]
Comparison: Vomiting: Moderate95% CI: [-0.9, 0.1]
Comparison: Muscle pain: Anyp-value: 0.27695% CI: [-1.3, 4.7]Miettinen and Nurminen
Comparison: Muscle pain: Mild95% CI: [-1.2, 2.8]
Comparison: Muscle pain: Moderate95% CI: [-1.4, 3.5]
Comparison: Muscle pain: Severe95% CI: [-1.2, 0.8]
Comparison: Joint pain: Anyp-value: 0.27395% CI: [-1.3, 4.6]Miettinen and Nurminen
Comparison: Joint pain: Mild95% CI: [-0.2, 3.6]
Comparison: Joint pain: Moderate95% CI: [-2.6, 2.4]
Comparison: Joint pain: Severe95% CI: [-0.9, 1]
Secondary
Number of Participants With Any Postoperative S. Aureus Surgical-site Infection (SSI-Superficial, Deep Incisional or Organ/Space) Occurred Within 180 Days After Surgery
SSI: infection at a surgical incision. Types of SSI in this outcome measure: Superficial SSI: Infection involved only skin and subcutaneous tissue of the incision, Deep incisional SSI: infection involved deep soft tissues of incision (e.g. fascial and muscle layers), Organ/space SSI: infection involved any part of body, excluding skin incision, fascia, or muscle layers, that was opened or manipulated during operative procedure. Overall number of participants with postoperative SSI (including superficial, deep incisional and/or organ/space SSI) caused by S. aureus, occurred within 180 days after elective open posterior spinal fusion surgery with multilevel instrumentation as confirmed by EAC have been reported.
Time frame: Day of surgery (Day 1) up to Day 180 after surgery
Population: PP efficacy population: all eligible participants, vaccinated as randomized, who underwent surgery per study-defined criteria within 9-90 days (inclusive) post vaccination (expanded from 10-60 days window in protocol), had no infection/malignancy at surgery and had no major protocol violation prior to reporting S. aureus infection.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Staphylococcus Aureus 4-antigen (SA4Ag) | Number of Participants With Any Postoperative S. Aureus Surgical-site Infection (SSI-Superficial, Deep Incisional or Organ/Space) Occurred Within 180 Days After Surgery | 25 Participants |
| Placebo | Number of Participants With Any Postoperative S. Aureus Surgical-site Infection (SSI-Superficial, Deep Incisional or Organ/Space) Occurred Within 180 Days After Surgery | 23 Participants |
95% CI: [-100.42, 40.8]
Secondary
Number of Participants With Any Postoperative S. Aureus Surgical-site Infection (SSI-Superficial, Deep Incisional or Organ/Space) Occurred Within 90 Days After Surgery
SSI: infection at a surgical incision. Types of SSI in this outcome measure: Superficial SSI: Infection involved only skin and subcutaneous tissue of the incision, Deep incisional SSI: infection involved deep soft tissues of incision (e.g. fascial and muscle layers), Organ/space SSI: infection involved any part of body, excluding skin incision, fascia, or muscle layers, that was opened or manipulated during operative procedure. Overall number of participants with postoperative SSI (including superficial, deep incisional and/or organ/space SSI) caused by S. aureus, occurred within 90 days after elective open posterior spinal fusion surgery with multilevel instrumentation as confirmed by EAC have been reported.
Time frame: Day of surgery (Day 1) up to Day 90 after surgery
Population: PP efficacy population: all eligible participants, vaccinated as randomized, who underwent surgery per study-defined criteria within 9-90 days (inclusive) post vaccination (expanded from 10-60 days window in protocol), had no infection/malignancy at surgery and had no major protocol violation prior to reporting S. aureus infection.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Staphylococcus Aureus 4-antigen (SA4Ag) | Number of Participants With Any Postoperative S. Aureus Surgical-site Infection (SSI-Superficial, Deep Incisional or Organ/Space) Occurred Within 90 Days After Surgery | 24 Participants |
| Placebo | Number of Participants With Any Postoperative S. Aureus Surgical-site Infection (SSI-Superficial, Deep Incisional or Organ/Space) Occurred Within 90 Days After Surgery | 22 Participants |
95% CI: [-104.06, 41.41]
Secondary
Number of Participants With Postoperative S. Aureus Blood Stream Infection (BSI) And/or Surgical-site Infection (SSI-Including Deep Incisional or Organ/Space) Occurred Within 180 Days After Surgery
BSI: clinical infection involved a recognized pathogen (S. aureus) cultured from 1 or more blood cultures or a commensal organism cultured from 2 or more blood cultures whether primary or secondary to infection at another site. SSI: infection at a surgical incision. Types of SSI in this outcome measure: Deep incisional SSI: infection involved deep soft tissues of incision (e.g. fascial and muscle layers), Organ/space SSI: infection involved any part of body excluding skin incision, fascia or muscle layers, that was opened or manipulated during operative procedure. Overall number of participants with postoperative BSI and/or SSI (including deep incisional or organ/space), caused by S. aureus, occurred within 180 days of post elective open posterior spinal fusion surgery with multilevel instrumentation, as confirmed by EAC have been reported. A participant may have met criteria for both BSI and SSI (deep incisional or organ/space).
Time frame: Day of surgery (Day 1) up to Day 180 after surgery
Population: PP efficacy population: all eligible participants, vaccinated as randomized, who underwent surgery per study-defined criteria within 9-90 days (inclusive) post vaccination (expanded from 10-60 days window in protocol), had no infection/malignancy at surgery and had no major protocol violation prior to reporting S. aureus infection.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Staphylococcus Aureus 4-antigen (SA4Ag) | Number of Participants With Postoperative S. Aureus Blood Stream Infection (BSI) And/or Surgical-site Infection (SSI-Including Deep Incisional or Organ/Space) Occurred Within 180 Days After Surgery | 14 Participants |
| Placebo | Number of Participants With Postoperative S. Aureus Blood Stream Infection (BSI) And/or Surgical-site Infection (SSI-Including Deep Incisional or Organ/Space) Occurred Within 180 Days After Surgery | 14 Participants |
95% CI: [-126.3, 55.81]