Prevention of S. Aureus Pneumonia Study in Mechanically Ventilated Subjects Who Are Heavily Colonized With S. Aureus.

Study Overview
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Brief Summary
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The purpose of this study is the prevention of Staphylococcus aureus pneumonia in mechanically ventilated subjects heavily colonized with S. aureus. Staphylococcus aureus is a human pathogenic bacterium that causes severe infections, including pneumonia and sepsis. Hospital-acquired bacterial pneumonia (HABP) caused by S. aureus, including ventilator-associated bacterial pneumonia (VABP) in mechanically ventilated subjects, is a significant public health threat despite efforts to optimize antibiotic treatment. ASN100 is an investigational monoclonal antibody product that targets the toxins produced by S. aureus to protect subjects from developing S. aureus pneumonia.

Detailed Description
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This is a double-blind, randomized, single-dose, placebo-controlled study of ASN100 for the prevention of S. aureus pneumonia in mechanically ventilated subjects who are heavily colonized with S. aureus. This will be a global study conducted at approximately 65 sites to assess the safety, tolerability, and efficacy of ASN100. Eligible subjects who meet all of the inclusion criteria and none of the exclusion criteria will be screened by semi-quantitative culture of an endotracheal aspirate (ETA) to identify those who are heavily colonized with S. aureus (3+ to 4+). Upon determination of eligibility, subjects will be randomized in a 1:1 ratio to 1 of 2 treatment groups, ASN100 or placebo.

Official Title
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A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Determine the Safety and Efficacy of a Single Dose of ASN100 for the Prevention of Staphylococcus Aureus Pneumonia in Heavily Colonized, Mechanically Ventilated Subjects

Conditions
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Pneumonia, Ventilator-associated, Pneumonia, Staphylococcal

Intervention / Treatment
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* Drug: ASN100
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - Subject is currently hospitalized and is mechanically ventilated endotracheally (i.e., orotracheal or nasotracheal) and, in the Investigator's opinion, will require ongoing ventilator support for at least 48 hours; Exclusion Criteria: Subject has a chest X-ray or thoracic computed tomography (CT) scan that is definitive for a diagnosis of pneumonia Subject has a known and documented ETA culture showing heavy colonization with a -Gram-negative organism at enrollment or at any time during the Screening period; Significant Neutropenia Severe non-pulmonary source of infection. Subjects with a known history or current (suspected) diagnosis of cytokine release syndrome associated with the administration of peptides, proteins, and/or antibodies.

Ages Eligible for Study
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Minimum Age: 18 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo administered as 2 separate intravenous (IV) infusions | Drug: Placebo<br>* Placebo<br>|
| Experimental: ASN100<br>ASN100 administered as 2 separate intravenous (IV) infusions | Drug: ASN100<br>* monoclonal antibody combination of ASN-1 and ASN-2<br>* Other names: ASN-1 and ASN-2;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of a Single Intravenous (IV) Dose of ASN100 | Percentage of subjects in the MITT population who have or have not developed S. aureus (SA) pneumonia after a single intravenous (IV) dose of ASN100, based on sponsor defined outcome (SDO1). For each arm, the empirical proportion is defined by a ratio, which is the number of SA pneumonia events divided by the total number of subjects in the arm. The inference about the difference of two population rates is based on the empirical counterpart; specifically, the point estimate, 95% confidence interval and p-value for the rate difference. Subjects discontinued from the study due to any cause prior to Day 22 were considered as not developing SA pneumonia for the primary efficacy analysis. | Incidence of S. aureus pneumonia up to but not including Day 22 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Mechanical Ventilation | Duration of mechanical ventilation during the first 21 days post-randomization for subjects in the Modified Intent-to-Treat (MITT) Population | 21 days | 
| Length of ICU Stay | Total length of ICU stay during the first 21 days post-randomization for subjects in the MITT Population | 21 days | 
| 28-day All-cause Mortality | 28-day all-cause mortality in the MITT Population | 28 days | 
| ASN-1 and ASN-2 Maximum Serum Concentration (Cmax) | The levels of ASN-1 and ASN-2 measured at completion of study medication infusion, and at 6 hr, 24 hr, Day 4, Day 7, Day 14, Day 22, and Day 90 (final study visit) in subjects who are hospitalized or are able to return to the clinic for blood sampling. | through day 90 | 
| ASN-1 and ASN-2 Time to Maximum Concentration (Tmax) in Serum | The levels of ASN-1 and ASN-2 measured at completion of study medication infusion, and at 6 hr, 24 hr, Day 4, Day 7, Day 14, Day 22, and Day 90 after completion | through day 90 | 
| ASN-1 and ASN-2 Area Under the Concentration-time Curve in Serum | The levels of ASN-1 and ASN-2 measured at completion of study medication infusion, and at 6 hr, 24 hr, Day 4, Day 7, Day 14, Day 22, and Day 90 after completion | through day 90 | 
| ASN-1 and ASN-2 Terminal Elimination Half-life (t1/2) in Serum | The levels of ASN-1 and ASN-2 measured at completion of study medication infusion, and at 6 hr, 24 hr, Day 4, Day 7, Day 14, Day 22, and Day 90 after completion | through day 90 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pneumonia, S. aureus, Mechanically ventilated