|E.1 Medical condition or disease under investigation |
|E.1.1||Medical condition(s) being investigated || |
|Prevention of nosocomial pneumonia |
|E.1.1.1||Medical condition in easily understood language || |
|Prevention of an infection of the lungs that develops within 48 hours or more of hospital admission and which was not developing at the time of admission. |
|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 ||21.1 |
|E.1.2||Level ||LLT |
|E.1.2||Classification code ||10052596 |
|E.1.2||Term ||Nosocomial pneumonia |
|E.1.2||System Organ Class ||100000004862 |
|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 evaluate the effect of suvratoxumab on reducing the incidence of nosocomial all-cause pneumonia. |
|E.2.2||Secondary objectives of the trial || |
|1. To evaluate the safety of a single IV dose of suvratoxumab. |
2. To evaluate the effect of suvratoxumab on reducing the incidence of nosocomial all-cause pneumonia or death.
3. To evaluate the effect of suvratoxumab on reducing the incidence of nosocomial S. aureus pneumonia.
4. To evaluate the effect of suvratoxumab on reducing the incidence of long-term nosocomial pneumonia caused by S. aureus.
5. To measure the effect of suvratoxumab on the magnitude of healthcare utilization.
6. To evaluate the serum pharmacokinetics (PK) of suvratoxumab.
7. To evaluate the serum Anti-Drug Antibody (ADA) responses to suvratoxumab.
|E.2.3||Trial contains a sub-study || No |
|E.3||Principal inclusion criteria || |
|1. Adult (18 [unless otherwise specified by local Country laws] to 65 years of age) or Adolescent (12 to < 18 years of age [unless otherwise specified by local Country laws]) at the time of screening. |
2. Written informed consent and written informed assent and any locally required authorization (e.g., Health Insurance Portability and Accountability Act [HIPPA] in the US, EU Data Privacy Directive in the EU) obtained from the subject/legally acceptable representative (LAR) prior to performing any protocol-related procedures, including screening evaluations.
3. Females of childbearing potential (inclusive of adolescents) who are sexually active with a non-sterilized male partner must have evidence of not being pregnant upon enrolment and have a negative pregnancy test prior to administration of investigational product.
- Females of childbearing potential are defined as those who are not surgically sterile (i.e., bilateral oophorectomy, or complete hysterectomy), premenarchal or postmenopausal (defined as 12 months with no menses without an alternative medical cause).
4. Tracheal or bronchial sample positive by polymerase chain reaction (PCR) for S. aureus within 36 hours prior to randomization. Note: the 36-hour window will be determined by the time of sample collection.
5. Currently intubated and on mechanical ventilation in the ICU.
6. Expected to remain intubated and mechanically ventilated for ≥ 3 days based on investigator estimate.
7. No diagnosis of new-onset pneumonia within 72 hours prior to randomization (subjects with evidence of resolved pneumonia will be eligible).
|E.4||Principal exclusion criteria|| |
|1. The study subject is moribund or unlikely to survive for a week post randomization despite delivery of adequate antibiotics and supportive care, based on clinical judgement by the PI. |
2. Acute confirmed or suspected active S. aureus disease at study enrolment and investigational product dosing (colonization is acceptable as per inclusion criterion #4).
3. Active pulmonary disease that would impair the ability to diagnose pneumonia, such as active tuberculosis or fungal disease, obstructing lung cancer, large empyema, cystic fibrosis, or acute respiratory distress syndrome with lung "white out".
4. Receipt of anti- S. aureus systemic antibiotics for > 48 hours within 72 hours prior to randomization that are considered active against the S. aureus strain with which the subject is colonized, or anticipated ongoing receipt of anti- S. aureus systemic antibiotics.
5. APACHE-II score ≥ 25 (if Glasgow Coma Scale [GCS] score is > 5) or ≥ 30 (if GCS score is ≤ 5), or SOFA score ≥ 9 at time of randomization.
- Note: Vasopressors only used to improve cerebral perfusion pressure (e.g., subarachnoid hemorrhage) will not be entered in the calculation of the cardiovascular component of the SOFA score.
6. Receipt of any investigational drug therapy within 30 days prior to randomization.
7. Previous receipt of a mAb within 60 days prior to randomization.
8. Subjects with a CD4 count of < 200 due to advanced human immunodeficiency virus (HIV) infection. Subjects with a history of HIV infection who have been on highly active antiretroviral therapy and asymptomatic from HIV infection for at least 6 months may be enrolled.
9. History of allergic disease or reactions likely to be exacerbated by any component of the investigational product.
10. Not able to complete long-term follow-up for at least 90 days post dose based on investigator judgment.
11. Pregnant female or nursing mother.
|E.5 End points |
|E.5.1||Primary end point(s)|| |
|Incidence of nosocomial all-cause pneumonia through 30 days post dose. |
|E.5.1.1||Timepoint(s) of evaluation of this end point|| |
|Any time through 30 days post dose. |
|E.5.2||Secondary end point(s)|| |
|1. TEAEs and clinical laboratory assessments through 30 days post dose, and TESAEs and TEAEs of special interest (TEAESI) through 90 days, and for a subset of subjects through 180 days post dose. |
2. Incidence of nosocomial all-cause pneumonia or death through 30 days post dose.
3. Incidence of nosocomial S. aureus pneumonia through 30 days post dose.
4. Incidence of nosocomial pneumonia caused by S. aureus through 90 days post dose.
5. Magnitude of healthcare utilization (e.g., duration of mechanical ventilation, duration of ICU stay, duration of hospital stay, number of and days of systemic antibiotic use) through 90 days post dose in all subjects and in a subset of subjects through 180 days post dose.
6. Suvratoxumab serum concentration and PK parameters through 30 days post dose, and in a subset of subjects through 90 days post dose.
7. Suvratoxumab ADA response in serum through 30 days post dose, and in a subset of subjects through 90 days post dose.
|E.5.2.1||Timepoint(s) of evaluation of this end point|| |
|1. Any time through 30 days post dose; any time through 90 days post dose; in a subset of subjects any time through 180 days post dose. |
2. Any time through 30 days post dose.
3. Any time through 30 days post dose.
4. Any time through 90 days post dose.
5. Any time through 90 days post dose; in a subset of subjects any time through 180 days post dose.
6. Any time through 30 days post dose; in a subset of subjects any time through 90 days post dose.
7. Any time through 30 days post dose; in a subset of subjects any time through 90 days post dose.
|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|| Yes |
|E.6.7||Pharmacodynamic|| Yes |
|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.220.127.116.11||Other trial type description|| |
|E.7.2||Therapeutic exploratory (Phase II)|| No |
|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.8.2.4||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||16 |
|E.8.5||The trial involves multiple Member States|| Yes |
|E.8.5.1||Number of sites anticipated in the EEA||65 |
|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|| |
|United States |
|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 || |
|The end of the trial is defined as the date of the last protocol - specified visit/ assessment (including telephone contact) for the last subject in the study. |
|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||6 |
|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||6 |