Safety, Pharmacokinetics and Efficacy of KBSA301 in Severe Pneumonia (S. Aureus)

Phase 1

Completed

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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
KBSA301, a monoclonal antibody dose 1	KBSA301	1 mg/kg KBSA301
Placebo	Placebo	KBSA301-placebo
KBSA301, a monoclonal antibody dose 2	KBSA301	3 mg/kg KBSA301
KBSA301, a monoclonal antibody dose 3	KBSA301	10 mg/kg KBSA301
KBSA301, a monoclonal antibody dose 4	KBSA301	20 mg/kg KBSA301

Primary Outcome Measures

Name	Time	Method
Efficacy Endpoint: All-Cause Mortality by Day 28	At Day 28 post infusion (Day 0)	A summary of the number (%) of patients who died on or before Day 28 (mITT population) is provided, by treatment group and overall.

Secondary Outcome Measures

Name	Time	Method
Efficacy: All-Cause Mortality (Day 7)	Patients who died during the specified timepoints (Day 7)	A summary of the number (%) of patients who died on or before timepoints Day 7 visit (mITT population) is provided, by treatment group (overall) and placebo.
Efficacy: All-Cause Mortality (Day 14)	Patients who died during the specified timepoints (Day 14)	A summary of the number (%) of patients who died on or before timepoints Day 14 visit (mITT population) is provided, by treatment group (overall) and placebo.
Efficacy: All-Cause Mortality (End Of Study [EOS])	Patients who died during the specified timepoints (by EOS), up to day 107	A summary of the number (%) of patients who died on or before timepoints Day EOS (mITT population) is provided, by treatment group (overall) and placebo.
Efficacy: All-Cause Mortality (Day 21)	Patients who died during the specified timepoints (Day 21)	A summary of the number (%) of patients who died on or before timepoints Day 21 visit (mITT population) is provided, by treatment group (overall) and placebo.

Locations (18): Site 11
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Brussels, Belgium
Site 34
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Colombes, France
Site 32
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Argenteuil, France
Site 16
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Liege, Belgium
Site 40
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Angouleme, France
Site 38
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Orleans, France
Site 51
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Barcelona, Spain
Site 81
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Oklahoma City, Oklahoma, United States
Site 31
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Limoges, France
Site 35
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La Roche Sur Yon, France
Site 52
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Barcelona, Spain
Site 37
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Nantes, France
Site 33
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Tours, France
Site 83
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Jacksonville, Florida, United States
Site 41
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Angers, France
Site 80
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Houston, Texas, United States
Site 39
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Lyon, France
Site 36
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Dijon, France