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

April 9, 2020 updated by: Aridis Pharmaceuticals, Inc.

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)

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.

Study Overview

Status

Completed

Conditions

Intervention / 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.

Study Type

Interventional

Enrollment (Actual)

48

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • AR301
EXPERIMENTAL: Placebo
KBSA301-placebo
Drug: Placebo
Placebo administered as a single intravenous infusion
Other Names:
  • Placebo KBSA301

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
At Day 28 post infusion (Day 0)

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Aridis Pharmaceuticals, Inc.

Investigators

  • Principal Investigator: Pierre-François M Laterre, MD, Université Catholique de Louvain, Brussels, Belgium

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2012

Primary Completion (ACTUAL)

May 1, 2016

Study Completion (ACTUAL)

September 1, 2016

Study Registration Dates

First Submitted

April 8, 2012

First Submitted That Met QC Criteria

April 28, 2012

First Posted (ESTIMATE)

May 1, 2012

Study Record Updates

Last Update Posted (ACTUAL)

April 24, 2020

Last Update Submitted That Met QC Criteria

April 9, 2020

Last Verified

March 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • KBSA301-001

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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