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

• ClinicalTrials.gov Identifier: NCT02388165
• Recruitment Status: Terminated
• First Posted: March 13, 2015
• Results First Posted: September 2, 2020
• Last Update Posted: January 5, 2021
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: March 9, 2015
• First Posted Date: March 13, 2015
• Results First Submitted Date: June 5, 2020
• Results First Posted Date: September 2, 2020
• Last Update Posted Date: January 5, 2021
• Actual Study Start Date: July 2, 2015
• Actual Primary Completion Date: June 26, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 17, 2020)

• 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.
• Number of Participants With Newly Diagnosed Chronic Medical Disorders From First Postoperative Evaluation on Day 42 Until Last Postoperative Evaluation on Day 180 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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 Serious Adverse Events (SAEs) From The Day of Surgery (Day 1) Until Last Postoperative Evaluation on Day 180 [ Time Frame: 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.

• Original Primary Outcome Measures (submitted: March 9, 2015): The number of subjects in each treatment group with postoperative S. aureus blood stream infections and/or deep incisional or organ/space surgical site infections occurring within 90 days of elective posterior instrumented lumbar spinal fusion [ Time Frame: 90 DAYS after surgery ]

Current Secondary Outcome Measures (submitted: August 17, 2020)

• 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 [ Time Frame: 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).
• Number of Participants With Any Postoperative S. Aureus Surgical-site Infection (SSI-Superficial, Deep Incisional or Organ/Space) Occurred Within 90 Days After Surgery [ Time Frame: 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 [ Time Frame: 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.

Original Secondary Outcome Measures (submitted: March 9, 2015)

• The number of subjects in each treatment group with postoperative S. aureus blood stream infections and/or deep incisional or organ/space surgical site infections occurring within 180 days of elective posterior instrumented lumbar spinal fusion [ Time Frame: 180 days after surgery ]
• The number of subjects in each treatment group with postoperative S. aureus surgical site infections occurring within 90 days of elective posterior instrumented lumbar spinal fusion [ Time Frame: 90 days after surgery ]
• The number of subjects in each treatment group with postoperative S. aureus surgical site infections occurring within 180 days of elective posterior instrumented lumbar spinal fusion [ Time Frame: 180 days after surgery ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety and Efficacy of SA4Ag Vaccine in Adults Having Elective Open Posterior Spinal Fusion Procedures With Multilevel Instrumentation
• Official Title: 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Prevention
• Condition: Staphylococcal Vaccine

Intervention

• Biological: Staphylococcus 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
  Other Name: Vaccine
• Other: Placebo
  Vaccine excipients reconstituted in 0.5mL water for injections. Administered via IM injection given 10 to 60 days prior to surgery

Study Arms

• Active Comparator: SA4Ag
  Staphylococcus aureus 4-antigen Vaccine
  Intervention: Biological: Staphylococcus aureus 4-Antigen (SA4Ag) Vaccine
• Placebo Comparator: Placebo
  Diluent (sterile water) for Placebo
  Intervention: Other: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: February 20, 2020): 3450
• Original Estimated Enrollment (submitted: March 9, 2015): 2600
• Actual Study Completion Date: June 27, 2019
• Actual Primary Completion Date: June 26, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 85 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Austria, Bulgaria, Canada, France, Germany, Hungary, Japan, Spain, Sweden, United Kingdom, United States
• Removed Location Countries: Romania

Administrative Information

• NCT Number: NCT02388165
• Other Study ID Numbers: B3451002; 2014-002644-40 ( EudraCT Number ); 6123K1-2001 ( Other Identifier: Alias Study Number ); STRIVE ( Other Identifier: Alias Study Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
• URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

• Current Responsible Party: Pfizer
• Original Responsible Party: Same as current
• Current Study Sponsor: Pfizer
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: November 2020