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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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)

Conditions
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Pneumonia Due to Staphylococcus Aureus

Intervention / Treatment
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* Drug: KBSA301
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: KBSA301, a monoclonal antibody dose 1<br>1 mg/kg KBSA301 | Drug: KBSA301<br>* KBSA301 administered as a single intravenous infusion at dose 1, 2, 3 and 4.<br>* Other names: AR301;|
| Experimental: KBSA301, a monoclonal antibody dose 2<br>3 mg/kg KBSA301 | Drug: KBSA301<br>* KBSA301 administered as a single intravenous infusion at dose 1, 2, 3 and 4.<br>* Other names: AR301;|
| Experimental: KBSA301, a monoclonal antibody dose 3<br>10 mg/kg KBSA301 | Drug: KBSA301<br>* KBSA301 administered as a single intravenous infusion at dose 1, 2, 3 and 4.<br>* Other names: AR301;|
| Experimental: KBSA301, a monoclonal antibody dose 4<br>20 mg/kg KBSA301 | Drug: KBSA301<br>* KBSA301 administered as a single intravenous infusion at dose 1, 2, 3 and 4.<br>* Other names: AR301;|
| Experimental: Placebo<br>KBSA301-placebo | Drug: Placebo<br>* Placebo administered as a single intravenous infusion<br>* Other names: Placebo KBSA301;|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy: All-Cause Mortality (End Of Study [EOS]) | 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. | Patients who died during the specified timepoints (by EOS), up to day 107 | 
| Efficacy: All-Cause Mortality (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. | Patients who died during the specified timepoints (Day 14) | 
| Efficacy: All-Cause Mortality (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. | Patients who died during the specified timepoints (Day 7) | 
| Efficacy: All-Cause Mortality (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. | Patients who died during the specified timepoints (Day 21) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pneumonia, Monoclonal antibody, Staphylococcus aureus