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)
Overview
- Phase
- Phase 1
- Intervention
- KBSA301
- Conditions
- Pneumonia Due to Staphylococcus Aureus
- Sponsor
- Aridis Pharmaceuticals, Inc.
- Enrollment
- 48
- Locations
- 18
- Primary Endpoint
- Efficacy Endpoint: All-Cause Mortality by Day 28
- Status
- Completed
- Last Updated
- 6 years ago
Overview
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.
Investigators
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
Arms & Interventions
KBSA301, a monoclonal antibody dose 1
1 mg/kg KBSA301
Intervention: KBSA301
KBSA301, a monoclonal antibody dose 2
3 mg/kg KBSA301
Intervention: KBSA301
KBSA301, a monoclonal antibody dose 3
10 mg/kg KBSA301
Intervention: KBSA301
KBSA301, a monoclonal antibody dose 4
20 mg/kg KBSA301
Intervention: KBSA301
Placebo
KBSA301-placebo
Intervention: Placebo
Outcomes
Primary Outcomes
Efficacy Endpoint: All-Cause Mortality by Day 28
Time Frame: 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 Outcomes
- Efficacy: All-Cause Mortality (Day 7)(Patients who died during the specified timepoints (Day 7))
- Efficacy: All-Cause Mortality (Day 14)(Patients who died during the specified timepoints (Day 14))
- Efficacy: All-Cause Mortality (End Of Study [EOS])(Patients who died during the specified timepoints (by EOS), up to day 107)
- Efficacy: All-Cause Mortality (Day 21)(Patients who died during the specified timepoints (Day 21))