Safety and Efficacy of SA4Ag Vaccine in Adults Having Elective Open Posterior Spinal Fusion Procedures With Multilevel Instrumentation

Study Overview
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Brief Summary
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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.

Official Title
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A PHASE 2B, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY TO EVALUATE THE SAFETY AND EFFICACY OF STAPHYLOCOCCUS AUREUS 4 ANTIGEN VACCINE (SA4AG) IN ADULTS UNDERGOING ELECTIVE OPEN POSTERIOR SPINAL FUSION PROCEDURES WITH MULTILEVEL INSTRUMENTATION

Conditions
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Staphylococcal Vaccine

Intervention / Treatment
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* Biological: Staphylococcus aureus 4-Antigen (SA4Ag) Vaccine
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: SA4Ag<br>Staphylococcus aureus 4-antigen Vaccine | Biological: Staphylococcus aureus 4-Antigen (SA4Ag) Vaccine<br>* SA4Ag vaccine reconstituted in 0.5mL water for injection. Administered via IM injection, once 10 to 60 days prior to surgery<br>* Other names: Vaccine;|
| Placebo Comparator: Placebo<br>Diluent (sterile water) for Placebo | Other: Placebo<br>* Vaccine excipients reconstituted in 0.5mL water for injections. Administered via IM injection given 10 to 60 days prior to surgery<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | Day of surgery (Day 1) up to Day 90 | 
| 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. | Within 10 days after Vaccination | 
| 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. | Within 10 days after Vaccination | 
| 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. | From vaccination up to Day of surgery (Day 1) (10-60 days after vaccination) | 
| 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. | From vaccination until Day 42 after surgery (52-102 days after vaccination) | 
| 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. | Day of surgery (Day 1) up to Day 42 after surgery | 
| 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. | Day 42 up to Day 180 (up to 138 days) | 
| 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. | From vaccination up to Day 180 after surgery (190-240 days after vaccination) | 
| 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. | From vaccination up to Day of surgery (Day 1) (10-60 days after vaccination) | 
| 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. | Day of surgery (Day 1) up to Day 180 after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | Day of surgery (Day 1) up to Day 180 after surgery | 
| 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. | Day of surgery (Day 1) up to Day 90 after surgery | 
| 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. | Day of surgery (Day 1) up to Day 180 after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Staphylococcal Vaccine, Post-operative Surgical Site Infection, Spinal Surgery, MRSA, Staphylococcus aureus