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

Primary Purpose

Pneumonia Due to Staphylococcus Aureus

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
KBSA301
Placebo
Sponsored by
Aridis Pharmaceuticals, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pneumonia Due to Staphylococcus Aureus focused on measuring Pneumonia, Monoclonal antibody, Staphylococcus aureus

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Site 83
  • Site 81
  • Site 80
  • Site 11
  • Site 16
  • Site 41
  • Site 40
  • Site 32
  • Site 34
  • Site 36
  • Site 35
  • Site 31
  • Site 39
  • Site 37
  • Site 38
  • Site 33
  • Site 51
  • Site 52

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

KBSA301, a monoclonal antibody dose 1

KBSA301, a monoclonal antibody dose 2

KBSA301, a monoclonal antibody dose 3

KBSA301, a monoclonal antibody dose 4

Placebo

Arm Description

1 mg/kg KBSA301

3 mg/kg KBSA301

10 mg/kg KBSA301

20 mg/kg KBSA301

KBSA301-placebo

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.

Full Information

First Posted
April 8, 2012
Last Updated
April 9, 2020
Sponsor
Aridis Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT01589185
Brief Title
Safety, Pharmacokinetics and Efficacy of KBSA301 in Severe Pneumonia (S. Aureus)
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)
Study Type
Interventional

2. Study Status

Record Verification Date
March 2020
Overall Recruitment Status
Completed
Study Start Date
May 2012 (undefined)
Primary Completion Date
May 2016 (Actual)
Study Completion Date
September 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Aridis Pharmaceuticals, Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pneumonia Due to Staphylococcus Aureus
Keywords
Pneumonia, Monoclonal antibody, Staphylococcus aureus

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
48 (Actual)

8. Arms, Groups, and Interventions

Arm Title
KBSA301, a monoclonal antibody dose 1
Arm Type
Experimental
Arm Description
1 mg/kg KBSA301
Arm Title
KBSA301, a monoclonal antibody dose 2
Arm Type
Experimental
Arm Description
3 mg/kg KBSA301
Arm Title
KBSA301, a monoclonal antibody dose 3
Arm Type
Experimental
Arm Description
10 mg/kg KBSA301
Arm Title
KBSA301, a monoclonal antibody dose 4
Arm Type
Experimental
Arm Description
20 mg/kg KBSA301
Arm Title
Placebo
Arm Type
Experimental
Arm Description
KBSA301-placebo
Intervention Type
Drug
Intervention Name(s)
KBSA301
Other Intervention Name(s)
AR301
Intervention Description
KBSA301 administered as a single intravenous infusion at dose 1, 2, 3 and 4.
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Placebo KBSA301
Intervention Description
Placebo administered as a single intravenous infusion
Primary Outcome Measure Information:
Title
Efficacy Endpoint: All-Cause Mortality by Day 28
Description
A summary of the number (%) of patients who died on or before Day 28 (mITT population) is provided, by treatment group and overall.
Time Frame
At Day 28 post infusion (Day 0)
Secondary Outcome Measure Information:
Title
Efficacy: All-Cause Mortality (End Of Study [EOS])
Description
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.
Time Frame
Patients who died during the specified timepoints (by EOS), up to day 107
Title
Efficacy: All-Cause Mortality (Day 14)
Description
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.
Time Frame
Patients who died during the specified timepoints (Day 14)
Title
Efficacy: All-Cause Mortality (Day 7)
Description
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.
Time Frame
Patients who died during the specified timepoints (Day 7)
Title
Efficacy: All-Cause Mortality (Day 21)
Description
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.
Time Frame
Patients who died during the specified timepoints (Day 21)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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 Immunosuppressive therapy Liver function deficiency Moribund clinical condition
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pierre-François M Laterre, MD
Organizational Affiliation
Université catholique de Louvain, Brussels, Belgium
Official's Role
Principal Investigator
Facility Information:
Facility Name
Site 83
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32209
Country
United States
Facility Name
Site 81
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Facility Name
Site 80
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Site 11
City
Brussels
Country
Belgium
Facility Name
Site 16
City
Liege
Country
Belgium
Facility Name
Site 41
City
Angers
Country
France
Facility Name
Site 40
City
Angouleme
Country
France
Facility Name
Site 32
City
Argenteuil
Country
France
Facility Name
Site 34
City
Colombes
Country
France
Facility Name
Site 36
City
Dijon
Country
France
Facility Name
Site 35
City
La Roche Sur Yon
Country
France
Facility Name
Site 31
City
Limoges
Country
France
Facility Name
Site 39
City
Lyon
Country
France
Facility Name
Site 37
City
Nantes
Country
France
Facility Name
Site 38
City
Orleans
Country
France
Facility Name
Site 33
City
Tours
Country
France
Facility Name
Site 51
City
Barcelona
Country
Spain
Facility Name
Site 52
City
Barcelona
Country
Spain

12. IPD Sharing Statement

Citations:
PubMed Identifier
30343314
Citation
Francois B, Mercier E, Gonzalez C, Asehnoune K, Nseir S, Fiancette M, Desachy A, Plantefeve G, Meziani F, de Lame PA, Laterre PF; MASTER 1 study group. Safety and tolerability of a single administration of AR-301, a human monoclonal antibody, in ICU patients with severe pneumonia caused by Staphylococcus aureus: first-in-human trial. Intensive Care Med. 2018 Nov;44(11):1787-1796. doi: 10.1007/s00134-018-5229-2. Epub 2018 Oct 21.
Results Reference
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Safety, Pharmacokinetics and Efficacy of KBSA301 in Severe Pneumonia (S. Aureus)

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