E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Staphylococcus aureus bacteremia Staphylococcus aureus mediastinitis |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10058887 |
E.1.2 | Term | Staphylococcus aureus bacteremia |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10066413 |
E.1.2 | Term | Staphylococcus aureus mediastinitis |
|
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) Primary Efficacy Objective: 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. For this study, a S. aureus deep sternal wound infection includes S. aureus mediastinitis or a S. aureus deep incisional surgical-site infection involving the sternal wound. (2) Primary Safety Objective: To evaluate the safety profile of a single dose of V710 administered to adult patients prior to cardiothoracic surgery.
|
|
E.2.2 | Secondary objectives of the trial |
(1) Secondary Efficacy Objective: 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) Secondary Efficacy Objective: 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.
|
|
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. 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.
|
|
E.4 | Principal exclusion criteria |
1. Patient developed an invasive S. aureus infection (e.g., bacteremia, endocarditis, pneumonia, mediastinitis, osteomyelitis, etc.) in the three months prior to study entry. 2. Patient’s underlying condition is sufficiently unstable so that there is a realistic (>50%) possibility that cardiothoracic surgery will be necessary within the 10 days following study entry/vaccination. 3. Patient is planning to undergo cardiac transplantation surgery or sternal debridement to remedy an infection resulting from a prior cardiothoracic surgery. 4. Patient has received any other investigational S. aureus vaccine or any investigational S. aureus antibodies within the 12 months prior to study entry. 5. Patient has a temperature of ≥100.4ºF (≥38.0ºC), oral equivalent, within 48 hours prior to study vaccination. 6. 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. 7. 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. 8. Patient is currently pregnant or breastfeeding, or planning to conceive at any time throughout the duration of the study (through postoperative Day 90). 9. Patient has a medical condition in which the expected survival is less than 90 days.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
(1) The primary efficacy endpoint is the proportion of patients with evidence of S. aureus bacteremia and/or S. aureus deep sternal wound infections at any time through postoperative Day 90. These primary endpoints will be defined as follows: S. aureus Bacteremia: A case of S. aureus bacteremia will be defined as ≥1 positive blood culture for S. aureus (regardless of the presence of clinical symptoms). S. aureus Deep Sternal Wound Infection: For this study, a S. aureus deep sternal wound infection includes S. aureus mediastinitis or a S. aureus deep incisional surgical-site infection involving the sternal wound. Each is defined separately below: A case of S. aureus mediastinitis will be defined as any infection that meets one of the following two criteria: A positive S. aureus culture from mediastinal tissue or fluid obtained during a surgical operation or needle aspiration; or Patient meets the following 2 criteria: 1. Purulent discharge from the mediastinal area (i.e., from mediastinal fluid or tissue and not only from more anterior sites [including skin, subcutaneous tissue, fascial layer, or muscle layer]) positive on culture for S. aureus, and 2. At least one of the following signs or symptoms with no other recognized cause: - Fever (>38ºC [or >100.4ºF]), - Chest pain, - Sternal instability, or - Radiographic evidence on either chest X-ray/CT of mediastinal widening. A case of S. aureus deep incisional surgical-site infection of the sternal wound will be defined as any infection that meets the following 2 criteria: S. aureus organisms isolated from an aseptically obtained culture of deep soft tissue (involving the fascial or muscle layers) but not from mediastinal tissue or fluid, and The patient has at least one of the following: 1. Purulent drainage from the deep incision (from fascial or muscle layers, but not from mediastinal space); 2. The sternal wound spontaneously dehisces or is deliberately opened by the surgeon; 3. The patient has at least one of the following signs or symptoms: fever (>38° C or >100.4ºF), chest pain, or chest tenderness; or An abscess or other evidence of infection involving the fascial or muscle layers is found on direct examination, during reoperation, or by histopathologic or radiologic examination (a stitch abscess, which is defined as minimal inflammation and discharge confined to the point of suture penetration, or other abscesses anterior to the fascial layers do not qualify). (2) The primary safety endpoint will be based on the proportion of vaccine-related serious adverse experiences observed throughout the course of the study (through postoperative Day 90) in each vaccination group. |
|
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 | No |
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 | 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.8.3 |
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.8.5 | 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 | Information not present in EudraCT |
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 |
|
E.8.7 | Trial has a data monitoring committee | No |
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
|
The end of the trial is based on the accruement of 76 cases of the primary efficacy endpoint (S. aureus bacteremia and/or S. aureus deep sternal wound infections [DSWI]), or upon demonstration of vaccine futility or early efficacy success at any of the three prespecified interim analyses, as described in the protocol. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 5 |