E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prevention of serious Staphylococcus aureus infection (S. aureus bacteremia and/or deep sternal wound infections/mediastinitis) |
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E.1.1.1 | Medical condition in easily understood language |
Staphylococcus aureus infection |
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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 | 13.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10069778 |
E.1.2 | Term | Vancomycin intermediate staphylococcus aureus infection |
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 |
(1) To demonstrate that a single dose of V710 administered prior to cardiothoracic surgery will reduce the proportion of adult patients who acquire S. aureus bacteremia and/or S. aureus deep sternal wound infections through postoperative day 90. (2) To evaluate the safety profile of a single dose of V710 administered to adult patients prior to cardiothoracic surgery. |
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E.2.2 | Secondary objectives of the trial |
(1) To demonstrate that a single dose of V710 administered prior to cardiothoracic surgery will reduce the proportion of adult patients who acquire any invasive S. aureus infection through postoperative day 90. (2) To demonstrate that a single dose of V710 administered prior to cardiothoracic surgery will reduce the proportion of adult patients who acquire any S. aureus surgical-site infection through postoperative day 90. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patient is 18 years of age or greater.
2. Patient is scheduled to undergo cardiothoracic surgery involving a full median sternotomy (not including cardiac transplantation surgery) within 14 to 60 days postvaccination.
3. Patient is able to understand all study procedures and agrees to participate in the study by providing written informed consent.
4. Patient intends to participate for the entire study duration (i.e., through postoperative Day 90 for the purposes of active efficacy surveillance for all patients; through postoperative Day 360 for long-term safety surveillance for all patients; and through postoperative Day 360 for long-term immunogenicity and nasal colonization surveillance for a subset of patients [N=400]).
5. Female patients of reproductive potential are required to have a negative urine or serum pregnancy test immediately prior to study vaccination. Female patients of reproductive potential must have been using an acceptable form of birth control for
two weeks prior to enrollment, and agree to use an acceptable method of birth control for one month postvaccination. Acceptable methods of birth control include use of hormonal contraceptives, intrauterine device (IUD), diaphragm with spermicide, contraceptive sponge, tubal ligation, condoms, or abstinence.
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E.4 | Principal exclusion criteria |
1. Patient developed invasive S. aureus infection (e.g., bacteremia, endocarditis, pneumonia, mediastinitis, osteomyelitis, etc.) in 3 months prior to study entry.
2. Patient’s underlying condition is sufficiently unstable so that there is a(>50%) possibility that cardiothoracic surgery will be necessary within 10 days following study entry/vaccination.
3. Patient is planning to undergo cardiothoracic surgery which does not involve a full median sternotomy (i.e., minimally invasive cardiothoracic surgery).
4. Patient is planning to undergo cardiac transplantation surgery or sternal debridement to remedy an infection resulting from a prior cardiothoracic surgery.
5. Patient has any type of ventricular-assist device in place at time of study entry.
6. Patient has a history of anaphylaxis to any of the vaccine components.
7. Patient has previously received V710 (in either this study or a previous V710 study).
8. Patient has received any other investigational S. aureus vaccine or any investigational S. aureus antibodies within the 12 months prior to study entry.
9. Patient has a temperature of ≥100.4ºF (≥38.0ºC), oral equivalent, within 48 hours prior to study vaccination.
10. Patient has received a live virus vaccine within 30 days prior to receipt of the study vaccine or is scheduled to receive any live virus vaccine within 30 days postvaccination.
11. Patient has received any other licensed vaccine (including inactivated or recombinant vaccines) within 14 days prior to receipt of the study vaccine or is scheduled to receive any other licensed vaccine (including non-live virus vaccines) within 30 days postvaccination. (NOTE: Influenza and pneumococcal vaccines may be administered during the study, but must be given at least 7 days prior to or at least 15 days after study vaccination).
12. Patient was administered any immunoglobulin within 90 days prior to study vaccination or is scheduled to receive such products at any time through postoperative Day 90.
13. Patient has received treatment with systemic (intramuscular, oral, or intravenous) corticosteroids (at a prednisone-equivalent dose of ≥20 mg daily), another immunosuppressive medication (e.g., calcineurin inhibitors, mycophenolate, azathioprine), or biological agents (e.g., rituximab) in the 14 days prior to study vaccination, or is anticipated to receive such medications for a chronic medical condition at any time through postoperative Day 90.
14. Patient has a known or suspected impairment of immunologic function including, but not limited to, the following conditions: autoimmune disease, moderate/severe hepatic insufficiency or cirrhosis, renal failure or insufficiency (on hemodialysis or peritoneal dialysis), immunoglobulin deficiency, or other congenital or acquired immunodeficiency, including HIV/AIDS.
15. Patient has a condition such as hemophilia, other severe coagulation disorders, or significantly impaired venous access, in which repeated venipuncture or injections pose more than minimal risk.
16. Patient is currently pregnant or breastfeeding, or planning to conceive at any time through postoperative Day 90.
17. Patient has a medical condition in which the expected survival is less than 90 days.
18. Patient has current evidence or a recent history (within the five years prior to study entry) of intravenous drug abuse.
19. Patient has participated in another clinical trial in the 4 weeks prior to study entry, or plans to participate in a treatment-based trial or another trial in which an invasive procedure is to be performed, at any time through postoperative Day 90. (NOTE: Participation in a non-interventional surveillance study is acceptable at anytime during the course of this trial).
20. Patient has a history of any condition that, in the opinion of the investigator, may pose an additional risk to the patient or confound the results of this study.
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E.5 End points |
E.5.1 | Primary end point(s) |
S. aureus Bacteremia and/or S. aureus deep sternal wound infection (DSWI), including mediastinitis. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Date of cardiothoracic surgery through Postoperative Day 90. |
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E.5.2 | Secondary end point(s) |
Any invasive S. aureus infection; Any S. aureus surgical-site infection. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Date of cardiothoracic surgery through Postoperative Day 90. |
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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 |
Immunogenicity; Health care resource utilization. |
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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) | Yes |
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 | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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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
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 80 |
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 |
Argentina |
Belgium |
Brazil |
Canada |
Chile |
Colombia |
Czech Republic |
Denmark |
Finland |
France |
Germany |
Guatemala |
Hungary |
Ireland |
Japan |
Korea, Democratic People's Republic of |
Malaysia |
Mexico |
New Zealand |
Norway |
Peru |
Poland |
Russian Federation |
Singapore |
Spain |
Sweden |
Taiwan |
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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Accrual of the required number of primary endpoints at one of the interim or final analyses, and confirmation by an independent Data & Safety Monitoring Board (DSMB) that the prespecified futility or success boundaries have been met. |
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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 | 7 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 7 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |