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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Aridis Pharmaceuticals, LLC
ClinicalTrials.gov Identifier:
NCT01589185
First received: April 8, 2012
Last updated: May 20, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Pneumonia Due to Staphylococcus Aureus
Drug: KBSA301
Drug: Placebo
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Aridis Pharmaceuticals, LLC:

Primary Outcome Measures:
  • Incidence of adverse events [ Time Frame: From drug administration up to 107 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Assessment of anti-drug-antibodies of KBSA301 [ Time Frame: Pre-dose and on days 15, 29, 57, and 107 post dose ] [ Designated as safety issue: Yes ]
  • Survival (all-cause mortality within 28 days after treatment) [ Time Frame: Days 15, 28, 57 and at day 107 ] [ Designated as safety issue: No ]
  • Changes in bacterial load from respiratory samples [ Time Frame: Predose and one additional sample obtained between Day 8 and Day 29 ] [ Designated as safety issue: No ]
  • Clinical Response of pneumonia: Cure [ Time Frame: Daily until Day 29 ] [ Designated as safety issue: No ]

Estimated Enrollment: 52
Study Start Date: April 2012
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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 Name: 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 Name: AR301
Experimental: Placebo
KBSA301-placebo
Drug: Placebo
Placebo administered as a single intravenous infusion
Other Name: Placebo KBSA301

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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01589185

Locations
Belgium
Site 11
Brussels, Belgium
Site 14
Genk, Belgium
Site 12
Ghent, Belgium
Site 15
Leuven, Belgium
Site 16
Liege, Belgium
Site 13
Louvain-La-Neuve, Belgium
Site 17
Yvoir, Belgium
France
Site 41
Angers, France
Site 40
Angouleme, France
Site 32
Argenteuil, France
Site 34
Colombes, France
Site 36
Dijon, France
Site 35
La Roche Sur Yon, France
Site 31
Limoges, France
Site 39
Lyon, France
Site 37
Nantes, France
Site 38
Orleans, France
Site 33
Tours, France
Spain
Site 51
Barcelona, Spain
Site 52
Bellvitge, Spain
Site 56
Getafe, Spain
Site 54
Las Palmas, Spain
Site 53
Madrid, Spain
Site 57
Madrid, Spain
Site 55
Palma de Mallorca, Spain
Site 58
Santander, Spain
Site 59
Valencia, Spain
Sponsors and Collaborators
Aridis Pharmaceuticals, LLC
Investigators
Study Director: Toni Perez, MD Aridis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Aridis Pharmaceuticals, LLC
ClinicalTrials.gov Identifier: NCT01589185     History of Changes
Other Study ID Numbers: KBSA301-001
Study First Received: April 8, 2012
Last Updated: May 20, 2014
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Belgium: Federal Agency for Medicinal Products and Health Products
Spain: Spanish Agency of Medicines

Keywords provided by Aridis Pharmaceuticals, LLC:
Pneumonia
Monoclonal antibody
Staphylococcus aureus

Additional relevant MeSH terms:
Pneumonia
Pneumonia, Staphylococcal
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Staphylococcal Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Pneumonia, Bacterial
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 18, 2014