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

Pneumonia, Ventilator-associated Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02940626
• Other study ID #: ASN100-201
• Secondary ID: 2016-002146-23
• Status: Terminated
• Phase: Phase 2
• Start date: November 2016
• Est. completion date: September 28, 2018

Study information

• Verified date: July 2019
• Source: Arsanis, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 155
• Est. completion date: September 28, 2018
• Est. primary completion date: July 19, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Pneumonia
• Pneumonia, Staphylococcal
• Pneumonia, Ventilator-associated

Intervention

Drug:
• ASN100
monoclonal antibody combination of ASN-1 and ASN-2
• Placebo
Placebo

Locations

Country	Name	City	State
Austria	Research Site 040-001	Wien
Austria	Research Site 040-002	Wien
Czechia	Research Site	Praha 10
Czechia	Research Site	Praha 6
France	Research Site	Argenteuil
France	Research Site	Lille Cedex
France	Research Site	Limoges
Georgia	Research Site 268-007	Rustavi
Georgia	Research Site 268-001	Tbilisi
Georgia	Research Site 268-002	Tbilisi
Georgia	Research Site 268-003	Tbilisi
Georgia	Research Site 268-004	Tbilisi
Georgia	Research Site 268-005	Tbilisi
Georgia	Research Site 268-006	Tbilisi
Georgia	Research Site 268-008	Tbilisi
Georgia	Research Site 268-009	Tbilisi
Georgia	Research Site 268-010	Tbilisi
Georgia	Research Site 268-011	Tbilisi
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Debrecen
Hungary	Research Site	Ózd
India	Research Site	Bangalore
India	Research Site	Hyderabad
India	Research Site	Jaipur
India	Research Site	Mahara
India	Research Site	Mumbai
India	Research Site	Pune
Israel	Research Site	H_olon
Israel	Research Site	Hadera
Israel	Research Site	Ramat Gan
Israel	Research Site	Tel Aviv
Poland	Research Site	Bialystok
Poland	Research Site	Bialystok
Poland	Research Site	Opole
Portugal	Research Site	Abrantes
Portugal	Research Site	Amadora
Portugal	Research Site	Lisboa
Portugal	Research Site	Lisboa
Portugal	Research Site	Loures
Portugal	Research Site	Viana do Castelo
Romania	Research Site	Bucharest
Romania	Research Site	Bucharest
Romania	Research Site	Craiova
Romania	Research Site	Timisoara
Russian Federation	Research Site	Arkhangel'sk
Russian Federation	Research Site	Barnaul
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Novosibirsk
Russian Federation	Research Site	Novosibirsk
Russian Federation	Research Site	Novosibirsk
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Sestroretsk
Serbia	Research Site 688-001	Belgrad
Serbia	Research Site 688-002	Belgrad
Serbia	Research Site 688-005	Belgrad
Serbia	Research Site 688-004	Kragujevac
Serbia	Research Site 688-003	Niš
South Africa	Research Site	Pretoria
South Africa	Research Site	Soweto
Spain	Research Site	Badalona
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Madrid
Spain	Research Site	Sevilla
Spain	Research Site	Tarragona
Spain	Research Site	Valencia
Ukraine	Research Site	Dnipro
Ukraine	Research Site	Ivano-Frankivs'k
Ukraine	Research Site	Kharkiv
Ukraine	Research Site	Lviv
United States	Research Site	Aurora	Colorado
United States	Research Site	Buffalo	New York
United States	Research Site	Burlington	Massachusetts
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Chattanooga	Tennessee
United States	Research Site	Chicago	Illinois
United States	Research Site	Chicago	Illinois
United States	Research Site	Cleveland	Ohio
United States	Research Site	Dallas	Texas
United States	Research Site	Georgetown	Kentucky
United States	Research Site	Hazard	Kentucky
United States	Research Site	Memphis	Tennessee
United States	Research Site	Phoenix	Arizona
United States	Research Site	Pittsburgh	Pennsylvania
United States	Research Site	Sacramento	California
United States	Research Site	Saint Louis	Missouri
United States	Research Site	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Arsanis, Inc.

Countries where clinical trial is conducted

United States,  Austria,  Czechia,  France,  Georgia,  Hungary,  India,  Israel,  Poland,  Portugal,  Romania,  Russian Federation,  Serbia,  South Africa,  Spain,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Length of ICU Stay	Total length of ICU stay during the first 21 days post-randomization for subjects in the MITT Population	21 days
Secondary	28-day All-cause Mortality	28-day all-cause mortality in the MITT Population	28 days
Secondary	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
Secondary	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
Secondary	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
Secondary	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