A Human Monoclonal Antibody Against Staphylococcus Aureus Alpha Toxin in Mechanically Ventilated Adult Subjects - 2

Study Overview
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Brief Summary
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Clinical trial looking at safety and efficacy of suvratoxumab in prevention of pneumonia caused by Staphylococcus aureus in high-risk patients

Detailed Description
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This is a Phase 3, randomized, double-blind, placebo-controlled study evaluating the efficacy of a single IV dose of suvratoxumab in mechanically ventilated subjects in the ICU who are at high risk for S. aureus infections and who are currently free of active S. aureus-related disease but are colonized with S. aureus in the LRT.

Official Title
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A Phase 3, Randomized, Double-blind, Placebo-controlled, Single-dose Study to Evaluate the Efficacy and Safety of Suvratoxumab in Mechanically Ventilated Adults and Adolescents for the Prevention of Nosocomial Pneumonia

Conditions
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Ventilator Associated Pneumonia, Staphylococcus Aureus

Intervention / Treatment
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* Biological: Suvratoxumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Colonized with Staphylococcus aureus; Expected to require prolonged intubation and mechanical ventilation, without any evidence of active pneumonia. Exclusion Criteria: Staphylococcal disease at randomisation; Lung injury score consistent with pneumonia; Chronic tracheostomy patients; The study subject is moribund Receipt of anti- S. aureus systemic antibiotics Active pulmonary disease

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a Phase 3, randomized, placebo-controlled, single-dose study.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AR-320 (Suvratoxumab)<br>Participants will receive a single intravenous (IV) dose of suvratoxumab on Day 0 of the study. | Biological: Suvratoxumab<br>* Monoclonal antibody<br>* Other names: MEDI4893;|
| Placebo Comparator: Placebo<br>Participants will receive a single IV dose of placebo to survatoxumab on Day 0 of the study. | Drug: Placebo<br>* Placebo contains only excipients<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of nosocomial all-cause pneumonia through 30 days post dose | All-cause pneumonia is based on clinical, radiographic, and microbiologic criteria. The percent reduction of the incidence of (% of patients with) nosocomial all-cause pneumonia, regardless of identified etiology, following administration of study drug through 30 days post dose | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with TEAE at 30 days | Treatment emergent adverse events (TEAE) are those adverse events (AEs, any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship) that occur or worsen during the treatment period, i.e., after the administration of study drug, through 30 days post dose | 30 days | 
| Number of participants with TESAE at 90 days | Treatment emergent serious adverse events (TESAE) are serious adverse events (SAEs, AEs resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience; persistent or significant disability/incapacity; congenital anomaly) that, as TEAEs, are present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug, through 90 days | 90 days | 
| Number of participants with TEAESI at 90 days | A TEAE of special interest (TEAESI) is an AE of scientific and medical interest specific to understanding of the study drug and may have required close monitoring and rapid communication by the investigator to the sponsor. An AESI may have been serious or non-serious. The time-frame is 90 days. | 90 days | 
| Number of Participants with Nosocomial all-cause pneumonia or death through 30 days post dose | All-cause pneumonia is based on clinical, radiographic, and microbiologic criteria. The percent reduction of the incidence of (% of patients with) nosocomial all-cause pneumonia, regardless of cause, or death following administration of study drug through 30 days post dose | 30 days | 
| Number of Participants with Nosocomial S. aureus pneumonia through 30 days post dose | S. aureus pneumonia is based on clinical, radiographic, and microbiologic criteria. The percent reduction of the incidence of (% of patients with) nosocomial S. aureus pneumonia following administration of study drug through 30 days post dose | 30 days | 
| Number of Participants with Nosocomial S. aureus pneumonia through 90 days post dose | S. aureus pneumonia is based on clinical, radiographic, and microbiologic criteria. The percent reduction of the incidence of (% of patients with) nosocomial S. aureus pneumonia following administration of study drug through 90 days post dose | 90 days | 
| Suvratoxumab Maximum Observed Serum Concentration (Cmax) | Maximum Observed Serum Concentration (Cmax) of suvratoxumab at Day 0 (Pre-dose, end of the infusion, 8 and 24 hours post dose), and on Days 7, 30 and 90. At Day 90 only for a subset of patients. | 90 days | 
| Suvratoxumab Area under the Plasma Concentration-Time Curve (AUC) | the area under the plasma concentration-time curve (AUC) will be measured from time 0 to Day 30 (AUC0-30), in all study subjects, and AUC from time 0 to Day 90 (AUC0-90) for a subset of subjects | 90 days | 
| Number of Participants With Positive Anti-Drug Antibodies (ADA) Titer to Suvratoxumab | The incidence of (number of patients with) positive anti-drug antibodies (ADA) titer to suvratoxumab will be assessed and summarized by number and percentage of subjects that are ADA positive at predose, Day 30 in all subjects and Day 90 in a subset of patients. | 90 days |