Clinical trial NCT01589185: Safety, Pharmacokinetics and Efficacy of KBSA301 in Severe Pneumonia (S. Aureus)
Official title: A Randomized, Double-blind, Placebo-controlled, Single Ascending Dose Study to Assess the Safety, Pharmacokinetics, Efficacy and Pharmacodynamics of KBSA301 in Severe Pneumonia (S. Aureus)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Pneumonia Due to Staphylococcus Aureus
Keywords: Pneumonia
Monoclonal antibody
Staphylococcus aureus
Lead sponsor: Aridis Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2012-05-01
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objectives of this study are to assess the safety, tolerability, pharmacokinetics, pharmacodynamics and clinical outcome of patients who have severe pneumonia caused by Staphylococcus aureus (S. aureus) after a single intravenous administration of KBSA301 in addition of standard of care antibiotic treatment.

Detailed description: S. aureus is a leading cause of bloodstream, skin, soft tissue, and lower respiratory tract infections worldwide. The frequencies of both nosocomial and community-acquired S. aureus infections have increased steadily over the years and the treatment of these infections has become more challenging due to the emergence of multi-drug resistant strains (e.g. methicillin-resistant Staphylococcus aureus).

S. aureus has several virulence factors that contribute to the pathogenesis of the infection. Amongst them, alpha-toxin that is involved in the pathogenesis of pneumonia, as it leads to apoptosis and cell lysis, in particular lymphocytes, macrophages, alveolar epithelial cells, pulmonary endothelium, and thrombocytes.

In spite of preventive measures for S. aureus infections and current medical treatment (mostly antibiotic therapy, alone or in combination), there is a clear unmet medical need in the clinic for additional treatment options. Passive immunotherapy with monoclonal antibodies may improve treatment options for severe and life-threatening infections like those caused by S. aureus.

Eligibility criteria: Inclusion Criteria:

* Adult male or female patients ≥ 18 years and ≤ 70 years of age
* Severe pneumonia caused by S. aureus (either methicillin-resistant or methicillin-sensitive) managed in an ICU
* APACHE II of ≤30 at the time of diagnosis
* Identification of S. aureus
* Written informed consent provided by the patient, the relatives or the designated trusted person and/or according to local guidelines

Exclusion Criteria:

* Women of child bearing potential are excluded from the participation from the study unless they have a negative pregnancy test at baseline and during the course of the study. Postmenopausal women or females that have been surgically sterilized are allowed to participate.
* Hypersensitivity to excipients or to any prescribed medication
* Severe neutropenia, lymphoma or anticipated chemotherapy
* Patients who have long-term tracheostomy
* Current or recent investigational drug (within 30 days of enrollment, or 5 half-lives of the investigational compound, whichever is longer)
* Presence of meningitis, endocarditis, or osteomyelitis
* Acquired immune deficiency syndrome (AIDS) with cluster of differentiation 4 (CD4) count \<200 cells/ml
* Known bronchial obstruction or a history of post-obstructive pneumonia.
* Active primary lung cancer or another malignancy metastatic to the lungs
* Cystic fibrosis, known or suspected Pneumocystis jiroveci pneumonia, or known or suspected active tuberculosis
* Immunosuppressive therapy
* Liver function deficiency
* Moribund clinical condition

Primary outcomes:
measure: Efficacy Endpoint: All-Cause Mortality by Day 28
timeFrame: At Day 28 post infusion (Day 0)
Secondary outcomes:
measure: Efficacy: All-Cause Mortality (End Of Study [EOS])
timeFrame: Patients who died during the specified timepoints (by EOS), up to day 107
measure: Efficacy: All-Cause Mortality (Day 14)
timeFrame: Patients who died during the specified timepoints (Day 14)
measure: Efficacy: All-Cause Mortality (Day 7)
timeFrame: Patients who died during the specified timepoints (Day 7)
measure: Efficacy: All-Cause Mortality (Day 21)
timeFrame: Patients who died during the specified timepoints (Day 21)
Other outcomes:
Locations:
city: Jacksonville
country: United States
facility: Site 83
state: Florida
city: Oklahoma City
country: United States
facility: Site 81
state: Oklahoma
city: Houston
country: United States
facility: Site 80
state: Texas
city: Brussels
country: Belgium
facility: Site 11
city: Liege
country: Belgium
facility: Site 16
city: Angers
country: France
facility: Site 41
city: Angouleme
country: France
facility: Site 40
city: Argenteuil
country: France
facility: Site 32
city: Colombes
country: France
facility: Site 34
city: Dijon
country: France
facility: Site 36
city: La Roche Sur Yon
country: France
facility: Site 35
city: Limoges
country: France
facility: Site 31
city: Lyon
country: France
facility: Site 39
city: Nantes
country: France
facility: Site 37
city: Orleans
country: France
facility: Site 38
city: Tours
country: France
facility: Site 33
city: Barcelona
country: Spain
facility: Site 51
city: Barcelona
country: Spain
facility: Site 52
Study officials:
affiliation: Université catholique de Louvain, Brussels, Belgium
name: Pierre-François M Laterre, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Francois B, Mercier E, Gonzalez C, Asehnoune K, Nseir S, Fiancette M, Desachy A, Plantefeve G, Meziani F, de Lame PA, Laterre PF; MASTER 1 study group. Safety and tolerability of a single administration of AR-301, a human monoclonal antibody, in ICU patients with severe pneumonia caused by Staphylococcus aureus: first-in-human trial. Intensive Care Med. 2018 Nov;44(11):1787-1796. doi: 10.1007/s00134-018-5229-2. Epub 2018 Oct 21.