E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prophylaxis for prevention of Post-operative S aureus infection |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10060945 |
E.1.2 | Term | Bacterial infection |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10004035 |
E.1.2 | Term | Bacterial infection due to staphylococcus aureus |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Primary Efficacy Objective
To assess the efficacy of SA4Ag in the prevention of postoperative S aureus BSI and/or deep incisional or organ/space SSI occurring within 90 days of elective open posterior spinal fusion procedures with multilevel instrumentation, in adults aged 18 to <86 years.
Primary Safety Objective
To describe the safety and tolerability of a single vaccination of SA4Ag in adults aged 18 to <86 years undergoing elective open posterior spinal fusion procedures with multilevel instrumentation, by measuring local reactions, systemic events, and AEs. |
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E.2.2 | Secondary objectives of the trial |
• To assess the efficacy of SA4Ag in the prevention of postoperative S aureus BSI and/or deep incisional or organ/space SSI occurring within 180 days of elective open posterior spinal fusion procedures with multilevel instrumentation, in adults 18 to <86 years of age.
• To assess the efficacy of SA4Ag in the prevention of postoperative S aureus SSI occurring within 90 days of elective open posterior spinal fusion procedures with multilevel instrumentation, in adults 18 to <86 years of age.
• To assess the efficacy of SA4Ag in the prevention of postoperative S aureus SSI occurring within 180 days of elective open posterior spinal fusion procedures with multilevel instrumentation, in adults 18 to <86 years of age. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subject must personally sign and date the informed consent document (ICD) indicating that the subject has been informed of all pertinent aspects of the study.
2. Subject must be aged 18 to <86 years at the time of enrollment.
3. Subject must be scheduled to undergo an elective open posterior spinal fusion procedure with multilevel instrumentation 10 to 60 days after study vaccination.
4. Subject must be available for the entire duration of the study, and willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures, including completion of the electronic diary (e-diary) for 10 days after study vaccination. (If surgery occurs on Day 10, then the e-diary does not need to be completed for that day).
5. Subject must be able to be contacted by telephone during study participation.
6. Male subjects and female subjects of childbearing potential and at risk for pregnancy must agree to use a highly effective method of contraception throughout the study.
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E.4 | Principal exclusion criteria |
1. Planned spinal fusion procedure requiring separate operations performed on separate days (ie, staged procedure).
2. Single-level spinal fusions without insertion of multilevel instrumentation (ie, surgical implantation of prosthetic material involving 2 or more motion segments).
3. Surgical indication of malignancy, infection, or acute or emergency trauma (ie, related to a traumatic incident occurring within 6 months prior to study enrolment).
4. History of major surgery (specifically, an open procedure that enters a body cavity, organ, or joint space) within 3 months prior to enrollment, or anticipated major surgery other than the index surgical procedure between study enrollment and completion of study participation.
5. History of any spinal surgery performed within 6 months prior to study enrollment.
6. History of any previous spinal surgery resulting in postoperative BSI or SSI.
7. Congenital or acquired immunodeficiency disorder, or rheumatologic disorder or other illness requiring chronic treatment with known immunosuppressant medications, including monoclonal antibodies, within the year prior to enrollment or the use of systemic corticosteroids (equivalent of ≥10 mg/day of prednisone) for >14 days within 30 days prior to study enrollment.
8. History of leukemia, lymphoma, or underlying bone marrow disorder (eg,
myelodysplasia, myeloma, myeloproliferative disorder) or history of bone marrow transplant.
9. Malignancy that required treatment with chemotherapy, immunotherapy, radiation therapy, or other antineoplastic target therapies within 24 months prior to study enrollment.
10. Any known or suspected malignancy to the spine.
11. Congenital, functional, or surgical asplenia.
12. End-stage renal disease (defined as requiring or anticipating requirement for hemodialysis, peritoneal dialysis, or renal transplant) or nephrotic syndrome.
13. Any contraindication to vaccination or vaccine components, including history of anaphylactic reaction to any vaccine or vaccine-related component.
14. Receipt of blood products or immunoglobulins (including monoclonal antibodies) within 6 months prior to study enrollment OR anticipated receipt of blood products or immunoglobulins (including monoclonal antibodies) prior to the index hospital admission.
15. Previous administration of S aureus vaccine or S aureus/Candida vaccine.
16. Antibiotic therapy for microbiologically confirmed ISA disease within 12 months prior to enrollment.
17. Participation in other studies involving investigational drug(s) (Phases 1-4) within 30 days before the current study begins and/or anticipated participation during the study.
18. Pregnant females, breastfeeding females, and males and females of childbearing potential who are unwilling or unable to use a highly effective method of contraception, for the duration of the study.
19. Presence of a colostomy, urostomy, tracheostomy, percutaneous gastrostomy tube, indwelling vascular or urinary catheter, central nervous system shunt, central nervous system implanted device, or spinal cord stimulator; OR anticipated presence of a colostomy, urostomy, tracheostomy, percutaneous gastrostomy tube, indwelling vascular or urinary catheter, central nervous system shunt, or central nervous system implanted device, or spinal cord stimulator prior to the index hospital admission.
20. Other severe acute or chronic medical or psychiatric condition (including drug and alcohol dependencies) 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.
21. Subjects who are investigational site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or subjects who are Pfizer employees directly involved in the conduct of the study.
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Efficacy Endpoint
The number of subjects in each vaccine group with postoperative S aureus BSI and/or deep incisional or organ/space SSI occurring within 90 days of elective open posterior spinal fusion procedures with multilevel instrumentation, as confirmed by the event adjudication committee (EAC).
Primary Safety Endpoints
• Number and proportion of subjects in each vaccine group with local reactions (redness, swelling, and pain) occurring within the 10-day period following study vaccination.
• Number and proportion of subjects in each vaccine group with systemic events (fever, fatigue, headache, vomiting, diarrhea, muscle or joint pain) occurring within the 10-day period following study vaccination.
• Number and proportion of subjects in each vaccine group with AEs reported during the following time periods:
- From vaccination until the day of surgery
- From vaccination until the Day 42 postoperative evaluation
- From the day of surgery until the Day 42 postoperative evaluation
- From the Day 42 postoperative evaluation until the day 180 postoperative evaluation (newly diagnosed chronic medical disorders)
• Number and proportion of subjects in each vaccine group with serious adverse events (SAEs) reported during the following time periods:
- From vaccination until the Day 180 postoperative evaluation
- From vaccination until the day of surgery
- From the day of surgery until the Day 180 postoperative evaluation |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• The number of subjects in each vaccine group with postoperative S aureus BSI and/or deep incisional or organ/space SSI occurring within 180 days of elective open posterior spinal fusion procedures with multilevel instrumentation.
• The number of subjects in each vaccine group with postoperative S aureus SSI occurring within 90 days of elective open posterior spinal fusion procedures with multilevel instrumentation.
• The number of subjects in each vaccine group with postoperative S aureus SSI occurring within 180 days of elective open posterior spinal fusion procedures with multilevel instrumentation. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Tolerability and immunogenicity |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Austria |
Brazil |
Bulgaria |
Canada |
France |
Germany |
Hungary |
India |
Japan |
Korea, Republic of |
Netherlands |
Romania |
Spain |
Sweden |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 27 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 21 |