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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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)

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 Summary:

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.


Sponsor: Aridis Pharmaceuticals, Inc.

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

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • 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 ]


Original Secondary Outcome: Same as current

Information By: Aridis Pharmaceuticals, Inc.

Dates:
Date Received: April 8, 2012
Date Started: April 2012
Date Completion:
Last Updated: September 21, 2016
Last Verified: September 2016