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

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

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.

Study Overview

• Status: Terminated
• Conditions: Pneumonia, Ventilator-associated; Pneumonia, Staphylococcal
• Intervention / Treatment: Drug: Placebo; Drug: ASN100

Detailed Description

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
• Enrollment (Actual): 155
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Wien, Austria, 1090
    • Research Site 040-001
  • Wien, Austria, 1090
    • Research Site 040-002
• Czechia
  • Praha 10, Czechia, 100 34
    • Research Site
  • Praha 6, Czechia, 169 02
    • Research Site
• France
  • Argenteuil, France, 95107
    • Research Site
  • Lille Cedex, France, 59037
    • Research Site
  • Limoges, France, 87042
    • Research Site
• Georgia
  • Rustavi, Georgia, 3700
    • Research Site 268-007
  • Tbilisi, Georgia, 114
    • Research Site 268-005
  • Tbilisi, Georgia, 141
    • Research Site 268-009
  • Tbilisi, Georgia, 144
    • Research Site 268-004
  • Tbilisi, Georgia, 144
    • Research Site 268-006
  • Tbilisi, Georgia, 159
    • Research Site 268-002
  • Tbilisi, Georgia, 159
    • Research Site 268-008
  • Tbilisi, Georgia, 159
    • Research Site 268-011
  • Tbilisi, Georgia, 160
    • Research Site 268-003
  • Tbilisi, Georgia, 163
    • Research Site 268-010
  • Tbilisi, Georgia, 191
    • Research Site 268-001
• Hungary
  • Budapest, Hungary, H-1134
    • Research Site
  • Budapest, Hungary, H-1135
    • Research Site
  • Debrecen, Hungary, H-4032
    • Research Site
  • Ózd, Hungary, 3600
    • Research Site
• India
  • Bangalore, India, 560002
    • Research Site
  • Hyderabad, India, 500096
    • Research Site
  • Jaipur, India, 302016
    • Research Site
  • Mahara, India, 440003
    • Research Site
  • Mumbai, India, 400008
    • Research Site
  • Pune, India, 411001
    • Research Site
• Israel
  • Hadera, Israel, 38100
    • Research Site
  • H̱olon, Israel, 5822012
    • Research Site
  • Ramat Gan, Israel, 5265601
    • Research Site
  • Tel Aviv, Israel, 6423906
    • Research Site
• Poland
  • Białystok, Poland, 15-027
    • Research Site
  • Białystok, Poland, 15-950
    • Research Site
  • Opole, Poland, 45-418
    • Research Site
• Portugal
  • Abrantes, Portugal, 2200
    • Research Site
  • Amadora, Portugal, 2720-276
    • Research Site
  • Lisboa, Portugal, 1649-035
    • Research Site
  • Lisboa, Portugal, 1500-461
    • Research Site
  • Loures, Portugal, 2674-514
    • Research Site
  • Viana do Castelo, Portugal, 4901-858
    • Research Site
• Romania
  • Bucharest, Romania, 21661
    • Research Site
  • Bucharest, Romania, 22328
    • Research Site
  • Craiova, Romania, 200642
    • Research Site
  • Timişoara, Romania, 300723
    • Research Site
• Russian Federation
  • Arkhangel'sk, Russian Federation, 163001
    • Research Site
  • Barnaul, Russian Federation, 656045
    • Research Site
  • Moscow, Russian Federation, 117997
    • Research Site
  • Novosibirsk, Russian Federation, 630008
    • Research Site
  • Novosibirsk, Russian Federation, 630047
    • Research Site
  • Novosibirsk, Russian Federation, 630075
    • Research Site
  • Saint Petersburg, Russian Federation, 196247
    • Research Site
  • Saint Petersburg, Russian Federation, 192242
    • Research Site
  • Saint Petersburg, Russian Federation, 194104
    • Research Site
  • Sestroretsk, Russian Federation, 197706
    • Research Site
• Serbia
  • Belgrad, Serbia, 11000
    • Research Site 688-001
  • Belgrad, Serbia, 11000
    • Research Site 688-002
  • Belgrad, Serbia, 11000
    • Research Site 688-005
  • Kragujevac, Serbia, 34000
    • Research Site 688-004
  • Niš, Serbia, 18000
    • Research Site 688-003
• South Africa
  • Pretoria, South Africa, 84
    • Research Site
  • Soweto, South Africa, 1860
    • Research Site
• Spain
  • Badalona, Spain, 8916
    • Research Site
  • Barcelona, Spain, 8035
    • Research Site
  • Barcelona, Spain, 28025
    • Research Site
  • Barcelona, Spain, 8036
    • Research Site
  • Barcelona, Spain, 8221
    • Research Site
  • Barcelona, Spain, 8907
    • Research Site
  • Madrid, Spain, 28040
    • Research Site
  • Sevilla, Spain, 41013
    • Research Site
  • Tarragona, Spain, 43005
    • Research Site
  • Valencia, Spain, 46026
    • Research Site
• Ukraine
  • Dnipro, Ukraine, 49005
    • Research Site
  • Ivano-Frankivs'k, Ukraine, 76008
    • Research Site
  • Kharkiv, Ukraine, 61176
    • Research Site
  • Lviv, Ukraine, 79010
    • Research Site
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Research Site
  • California
    • Sacramento, California, United States, 95817
      • Research Site
    • San Francisco, California, United States, 94110
      • Research Site
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Research Site
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Research Site
    • Chicago, Illinois, United States, 60611
      • Research Site
  • Kentucky
    • Georgetown, Kentucky, United States, 40324
      • Research Site
    • Hazard, Kentucky, United States, 41701
      • Research Site
  • Massachusetts
    • Burlington, Massachusetts, United States, 01805
      • Research Site
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Research Site
  • New York
    • Buffalo, New York, United States, 14215
      • Research Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28207
      • Research Site
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Research Site
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15240
      • Research Site
  • Tennessee
    • Chattanooga, Tennessee, United States, 37408
      • Research Site
    • Memphis, Tennessee, United States, 38163
      • Research Site
  • Texas
    • Dallas, Texas, United States, 75390
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Arsanis, Inc.
• Investigators: Study Director: Arsanis, Inc, Arsanis, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2016
• Primary Completion (Actual): July 19, 2018
• Study Completion (Actual): September 28, 2018

Study Registration Dates

• First Submitted: October 17, 2016
• First Submitted That Met QC Criteria: October 20, 2016
• First Posted (Estimate): October 21, 2016

Study Record Updates

• Last Update Posted (Actual): July 31, 2019
• Last Update Submitted That Met QC Criteria: July 10, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: Pneumonia; Mechanically ventilated; S. aureus
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Disease Attributes; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Cross Infection; Iatrogenic Disease; Staphylococcal Infections; Pneumonia, Bacterial; Healthcare-Associated Pneumonia; Pneumonia; Pneumonia, Ventilator-Associated; Pneumonia, Staphylococcal
• Other Study ID Numbers: ASN100-201; 2016-002146-23 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No