| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Active immunisation for the prevention of S. aureus infection (SSTI/Surgical Site Infection [SSI]/ Blood Stream Infection [BSI]) |
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| E.1.1.1 | Medical condition in easily understood language |
| S. aureus is a gram-positive bacterium causing a spectrum of illnesses varying from mild to life-threatening diseases and it is considered as a major cause of morbidity and mortality. |
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| E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
| MedDRA Classification |
| 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 |
• To assess safety and reactogenicity of investigational S. aureus vaccine
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|
| E.2.2 | Secondary objectives of the trial |
• To evaluate vaccine efficacy (VE) in the prevention of recurrent culture confirmed S. aureus SSTIs compared to placebo
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
All subjects must satisfy all the following criteria at study entry:
- Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol (e.g. completion of the diary cards, return for follow-up visits).
- Written or witnessed informed consent obtained from the subject prior to performance of any study specific procedure.
- Subject satisfying screening requirements.
- Subjects who, after the nature of the study has been explained to them, have shown adequate comprehension of the study procedures and knowledge of study.
- A male or female:
- Dose escalation and safety lead-in phase: Aged between 18 and 50 years of age, inclusive, at the time of first vaccination.
- PoP phase: Aged between 18 and 64 years of age, inclusive, at the time of first vaccination.
- Female subjects of non-childbearing potential may be enrolled in the study. Non-childbearing potential is defined as pre-menarche, current bilateral tubal ligation or occlusion, hysterectomy, bilateral ovariectomy or post-menopause.
- Female subjects of childbearing potential may be enrolled in the study, if the subject:
- has practiced adequate contraception for 30 days prior to vaccination,
- has a negative pregnancy test on the day of enrolment, and
- has agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of the vaccination series.
Additional inclusion criteria only for subjects to be enrolled in the dose-escalation safety lead-in screening epoch:
- Healthy subjects as established by medical history, clinical examination and laboratory assessment.
Additional inclusion criteria only for subjects to be enrolled in the PoP screening epoch:
- Healthy subjects as established by medical history and clinical examination before entering into the study with an ongoing SSTI suspected to be caused by S. aureus, as diagnosed by investigator (before randomization subjects have to be treated until clinical resolution of culture confirmed SSTI caused by S. aureus). SSTI must be amenable to microbiological culturing per standard clinical practice (i.e. recovery of drainage sample from abscess or suppurative cellulitis).
OR
- Healthy subjects as established by medical history and clinical examination before entering into the study with an ongoing S. aureus SSTI (i.e. S. aureus is the most likely cause), as confirmed by a S. aureus positive culture performed outside the study procedures and not earlier than 30 days prior to Informed Consent Form signature. Before randomisation subjects have to be treated until clinical resolution of the culture confirmed SSTI caused by S. aureus. These subjects will be enrolled whether they have or have not already started specific treatment of the infection. In case they have not started the treatment, this will be then given in compliance with the standard medical practice for the management of S. aureus SSTIs and the choice and judgment of the most appropriate treatment will be applied by the investigator, outside the study procedures. |
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| E.4 | Principal exclusion criteria |
All subjects at study entry
- BMI >40 kg/m2
- History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine
- Hypersensitivity to latex
- Recurrent history of uncontrolled neurological disorders or seizures
- History of potential immune-mediated disease (pIMD)
- Clinical conditions that in the investigator’s opinion represent a contraindication to intramuscular vaccination and blood draws
- Known bleeding diathesis or any condition that may be associated with a prolonged bleeding time
- Use of any investigational or non-registered product (drug, vaccine or medical device) other than the study vaccine(s) within 30 days before the first dose of study vaccine(s)/placebo (Day -29 to Day 1), or during the study period
- Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs during the period starting 3 months prior to the first vaccine/placebo dose
- Cytotoxic therapy (e.g., medications used during cancer chemotherapy)
- Administration of long-acting immune-modifying drugs at any time during the study period (e.g. infliximab)
- Administration of immunoglobulins and/or any blood products or plasma derivatives within 3 months before the first dose of study vaccine or during the study period
- Planned administration/administration of a vaccine not foreseen by the study protocol in the period starting 15 days before the first dose and ending 15 days after the last dose of vaccine(s) administration* with the exception of any non-adjuvanted influenza vaccine which may be administered ≥7 days before or after each study vaccination
*In case an emergency mass vaccination for an unforeseen public health threat (e.g.: a pandemic) is organised by the public health authorities, outside the routine immunisation program, the time period described above can be reduced if necessary for that vaccine provided it is licensed and used according to its Product Information.
- Concurrently participating in another clinical study, in which the subject has been or will be exposed to an investigational or a non-investigational vaccine/product (drug or medical device)
- Received a vaccine against S. aureus
- Pregnant or lactating female
- Female planning to become pregnant or planning to discontinue contraceptive precautions before 2 months after completion of the vaccination series
- History of chronic alcohol consumption and/or drug abuse
- Any study personnel or immediate dependents, family, or household member
All subjects at the time of vaccination
- Any clinically significant hematological (hemoglobin level, white blood cell, lymphocyte, neutrophil, eosinophil, platelet count and red blood cell count) and/or biochemical (alanine aminotransferase [ALT], aspartate aminotransferase [AST], creatinine) laboratory abnormality
Additional exclusion criteria applied only for dose-escalation safety lead-in
- Any active or ongoing illness at screening or time of injection
- History of any serious chronic or progressive disease according to the judgment of the investigator
Additional exclusion criteria applied only for PoP at study entry
- Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination
- Major congenital defects, as assessed by the investigator
- Acute or chronic, clinically significant pulmonary, cardiovascular*, hepatic or renal functional abnormality, neoplasm, diabetes type 1 and uncontrolled diabetes type 2*, as determined by physical examination or laboratory screening tests
* Note: Well-controlled type 2 diabetes mellitus (HbA1c <7%) and well-controlled arterial hypertension (blood pressure <140/90 mmHg) can be considered for inclusion in the study.
- Any behavioral or cognitive impairment or psychiatric disease that, in the opinion of the investigator, may interfere with the subject's ability to participate in the study
- Individuals at risk for severe or life-threatening SSTIs (e.g., lymphatic or venous insufficiency, liver and kidney disease, IV drug use, etc.)
- Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the subject due to participation in the study
Additional exclusion criteria applied only for PoP at vaccination
- Microbiological test results of drainage suggest that the SSTI etiology could be other than infection with S. aureus |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
1. Number of participants with solicited local adverse events (AEs) (any, grade 3)
2. Number of participants with solicited local adverse events (AEs) (any, grade 3)
3. Number of participants with solicited general AEs (any, grade 3)
4. Number of participants with solicited general AEs (any, grade 3)
5. Number of participants with unsolicited AEs (any, grade 3, related, related grade 3)
6. Number of participants with unsolicited AEs (any, grade 3, related, related grade 3)
7. Number of participants with serious AEs (SAEs) (any, grade 3, related, related grade 3)
8. Number of participants with serious AEs (SAEs) (any, grade 3, related, related grade 3)
9. Number of participants with potential immune-mediated diseases (PIMDs) (any, grade 3, related, related grade 3)
10. Number of participants with potential immune-mediated diseases (PIMDs) (any, grade 3, related, related grade 3)
11. Number of participants with haematological and biochemical laboratory abnormalities and changes from the baseline values
12. Number of participants with haematological and biochemical laboratory abnormalities and changes from the baseline values |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
1, 3. During 7 days after the first dose (Days 1 to 8)
2, 4. During 7 days after the second dose (Days 61 to 68)
5. During 30 days after the first dose (Days 1 to 31)
6. During 30 days after the second dose (Days 61 to 91)
7, 9. Throughout the study period [from Day 1 (day of vaccination) until Day 366]
8, 10. Throughout the study period [from Day 1 (day of vaccination) until Day 426]
11. At Day 8 (7 days after the first dose)
12. At Day 68 (7 days after the second dose) |
|
| E.5.2 | Secondary end point(s) |
1. Number of participants with at least one culture confirmed case of recurrent S. aureus SSTI
2. Number of participants with at least one culture confirmed case of recurrent S. aureus SSTI
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Starting from Day 75 (i.e.14 days after the second dose) up to Day 426 (12 months after the second dose).
2. Starting from Day 15 (i.e. 14 days after the first dose) up to Day 426 (12 months after the second dose).
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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 |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Yes |
| E.7.1.1 | First administration to humans | Yes |
| 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 | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| 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 |
| Sequential; Observer-blind (Dose-escalation safety lead-in & PoP vaccination epoch) |
|
| 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 | 10 |
| 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 | 7 |
| E.8.5 | The trial involves multiple Member States | No |
| 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 |
| Australia |
| India |
| New Zealand |
| South Africa |
| United States |
| Poland |
| Russian Federation |
| United Kingdom |
|
| 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
|
| Last subject last visit (LSLV) (Visit 10). |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 11 |
| E.8.9.1 | In the Member State concerned days | 11 |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 9 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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