Safety, Pharmacokinetics and Efficacy of KBSA301 in Severe Pneumonia (S. Aureus) - Full Text View

Purpose

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.

Condition	Intervention	Phase
Pneumonia Due to Staphylococcus Aureus	Drug: KBSA301 Drug: Placebo	Phase 1 Phase 2


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) Primary Purpose: Treatment
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)

Resource links provided by NLM:

MedlinePlus related topics: Pneumonia

U.S. FDA Resources

Further study details as provided by Aridis Pharmaceuticals, Inc.:

Primary Outcome Measures:

Incidence of adverse events [ Time Frame: From drug administration up to 107 days ]

Secondary Outcome Measures:

Area Under the Curve (AUC) in plasma of KBSA301 after a single-dose intravenous administration [ Time Frame: Predose and 1, 2, 4, 12, 24, 48 hours after start of infusion, and on Days 8, 15, 29, 57, 85, and 107 post dose ]
Maximum concentration (Cmax) in plasma of KBSA301 after a single-dose intravenous administration [ Time Frame: Predose and 1, 2, 4, 12, 24, 48 hours after start of infusion, and on Days 8, 15, 29, 57, 85, and 107 post dose ]
Half-life in plasma of KBSA301 after a single-dose intravenous administration [ Time Frame: Predose and 1, 2, 4, 12, 24, 48 hours after start of infusion, and on Days 8, 15, 29, 57, 85, and 107 post dose ]
Assessment of anti-drug-antibodies of KBSA301 [ Time Frame: Pre-dose and on days 15, 29, 57, and 107 post dose ]
Survival (all-cause mortality within 28 days after treatment) [ Time Frame: Days 15, 28, 57 and at day 107 ]
Changes in bacterial load from respiratory samples [ Time Frame: Predose and one additional sample obtained between Day 8 and Day 29 ]
Clinical Response of pneumonia: Cure [ Time Frame: Daily until Day 29 ]


Enrollment:	48
Study Start Date:	April 2012
Study Completion Date:	September 2016
Primary Completion Date:	May 2016 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: KBSA301, a monoclonal antibody dose 1 1 mg/kg KBSA301	Drug: KBSA301 KBSA301 administered as a single intravenous infusion at dose 1, 2, 3 and 4. Other Name: AR301
Experimental: KBSA301, a monoclonal antibody dose 2 3 mg/kg KBSA301	Drug: KBSA301 KBSA301 administered as a single intravenous infusion at dose 1, 2, 3 and 4. Other Name: AR301
Experimental: KBSA301, a monoclonal antibody dose 3 10 mg/kg KBSA301	Drug: KBSA301 KBSA301 administered as a single intravenous infusion at dose 1, 2, 3 and 4. Other Name: AR301
Experimental: KBSA301, a monoclonal antibody dose 4 20 mg/kg KBSA301	Drug: KBSA301 KBSA301 administered as a single intravenous infusion at dose 1, 2, 3 and 4. Other Name: AR301
Experimental: Placebo KBSA301-placebo	Drug: Placebo Placebo administered as a single intravenous infusion Other Name: Placebo KBSA301

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


Ages Eligible for Study:	18 Years to 80 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01589185

Locations


United States, Florida
Site 83
Jacksonville, Florida, United States, 32209
United States, Oklahoma
Site 81
Oklahoma City, Oklahoma, United States, 73104
United States, Texas
Site 80
Houston, Texas, United States, 77030
Belgium
Site 11
Brussels, Belgium
Site 16
Liege, Belgium
France
Site 41
Angers, France
Site 40
Angouleme, France
Site 32
Argenteuil, France
Site 34
Colombes, France
Site 36
Dijon, France
Site 35
La Roche Sur Yon, France
Site 31
Limoges, France
Site 39
Lyon, France
Site 37
Nantes, France
Site 38
Orleans, France
Site 33
Tours, France
Spain
Site 51
Barcelona, Spain
Site 52
Bellvitge, Spain

Sponsors and Collaborators

Aridis Pharmaceuticals, Inc.

Investigators


Principal Investigator:	Pierre-François Laterre, MD	Université catholique de Louvain, Brussels, Belgium

More Information


Responsible Party:	Aridis Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:	NCT01589185 History of Changes
Other Study ID Numbers:	KBSA301-001
Study First Received:	April 8, 2012
Last Updated:	September 21, 2016

Keywords provided by Aridis Pharmaceuticals, Inc.:


Pneumonia Monoclonal antibody Staphylococcus aureus

Additional relevant MeSH terms:


Pneumonia Pneumonia, Staphylococcal Lung Diseases Respiratory Tract Diseases Respiratory Tract Infections Staphylococcal Infections Gram-Positive Bacterial Infections	Bacterial Infections Pneumonia, Bacterial Antibodies Immunoglobulins Antibodies, Monoclonal Immunologic Factors Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 22, 2017