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

Phase 2TerminatedNCT02940626

Arsanis, Inc.155 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Enrollment

155

Conditions

Pneumonia, Ventilator-associated

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (93)

Research Site

Phoenix, Arizona, United States

Research Site

Sacramento, California, United States

Research Site

San Francisco, California, United States

Research Site

Aurora, Colorado, United States

Research Site

Chicago, Illinois, United States

Research Site

Outcomes

Primary Outcomes

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.

Time frame: Incidence of S. aureus pneumonia up to but not including Day 22

Secondary Outcomes

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

Time frame: 21 days

Length of ICU Stay

Total length of ICU stay during the first 21 days post-randomization for subjects in the MITT Population

Time frame: 21 days

28-day All-cause Mortality

28-day all-cause mortality in the MITT Population

Time frame: 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.

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: through day 90

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

Overview

Conditions

Interventions

Eligibility

Locations (93)

Outcomes

Primary Outcomes

Secondary Outcomes