Back to resultsA Study of the Safety and Efficacy of 514G3 in Subjects Hospitalized With Bacteremia Due to Staphylococcus Aureus
Primary Purpose
Staphylococcus Aureus Bacteremia
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
514G3
Placebo
Standard IV antibiotic therapy
Sponsored by
About this trial
This is an interventional treatment trial for Staphylococcus Aureus Bacteremia focused on measuring Staph, antibody
Eligibility Criteria
Inclusion Criteria:
- One or more blood cultures positive for staphylococcus aureus within 2 days of initiating treatment with 514G3.
- Temperature ≥ 38.0°C
- Age ≥18, male or female subjects.
- Adequate renal function, defined by serum creatinine ≤ 2 times the upper limit of normal (ULN).
- Adequate hepatic function
- Adequate bone marrow function
- For women of childbearing potential (WOCBP), a negative serum pregnancy test result at Screening.
- Signed and dated institutional review board (IRB)/ Ethics Committee (EC)-approved informed consent before any protocol-specific screening procedures are performed.
- Expected survival of at least 2 months.
Exclusion Criteria:
- Polymicrobial bacteremia.
- Known or suspected osteomyelitis or meningitis.
- Patients that are being mechanically ventilated as a result of a pulmonary infection at the time of screening. Mechanical ventilation for other reasons, such as trauma, is acceptable.
- Presence of any removable infection source (e.g., intravascular line, abscess, or prosthesis) that will not be removed or debrided within 3 days after randomization.
- Definite or possible left-sided endocarditis, by Modified Duke Criteria, based on screening echocardiogram. Subjects with suspected right-sided endocarditis are permitted.
- Need for emergent valve surgery at the time of screening, and/or the presence of decompensated heart failure or cardiogenic shock.
- Dementia or altered mental status that would prohibit the understanding or rendering of informed consent.
- Infection with human immunodeficiency virus (HIV) and a CD4 count <200 cells/mm3.
- Subjects with history of hypersensitivity to compounds of similar chemical or biologic composition to 514G3 or any component of its formulations.
- Women who are pregnant or breastfeeding.
Sites / Locations
- XBiotech Investigative Site
- XBiotech Investigative Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
514G3
Placebo
Arm Description
Phase I of the study will include a single dose of 514G3 at three different dose levels. Phase II utilizes a single dose of 514G3 at the highest dose level. Standard antibiotic therapies will be used in both phases.
Both Phase I and II will include a single dose of placebo in addition to standard antibiotic therapies.
Outcomes
Primary Outcome Measures
Phase I: Determination of the Maximum Tolerated Dose
The highest dose administered with no more than one dose limiting toxicity
Phase II: Safety and tolerability
The incidence of adverse events, serious adverse events, and laboratory abnormalities will be compared between the 514G3 arm and the placebo arm.
Secondary Outcome Measures
Determination of the serum half-life of 514G3
Serum levels of 514G3 will be measured at protocol specified timepoints to determine the half-life, and to ensure clearance of the antibody during the follow up period after dosing.
Duration of Fever
Length of hospitalization
Time to sterile culture from date of randomization
The time to sterile culture is the interval in days from the first dose of study drug until 2 consecutive days of negative blood cultures has occurred. The difference in this interval will be compared between patients randomized to placebo and those who received the highest dose of 514G3
Incidence of Serious Adverse Events
Differences in the incidence of SAEs between the 514G3 and placebo arms will be compared.
Opsonophagocytosis Assay
Serum samples from patients will be assessed with an in vitro opsonophagocytosis assay which measures the ability of the serum to mediate uptake of staph aureus by white blood cells. Differences in the levels of activity will be compared between treatment and placebo
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02357966
Brief Title
A Study of the Safety and Efficacy of 514G3 in Subjects Hospitalized With Bacteremia Due to Staphylococcus Aureus
Official Title
A Phase I-II Study of the Safety and Efficacy of a True Human Antibody, 514G3, in Subjects Hospitalized With Bacteremia Due to Staphylococcus Aureus
Study Type
Interventional
2. Study Status
Record Verification Date
February 2017
Overall Recruitment Status
Completed
Study Start Date
May 2015 (Actual)
Primary Completion Date
January 2017 (Actual)
Study Completion Date
February 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
XBiotech, Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study will evaluate the maximum safe dose of the true human monoclonal antibody, 514G3, in the treatment of patients with Staphylococcus Aureus bacteremia. Preliminary evidence of efficacy will be evaluated as well. Patients will receive 514G3 plus antibiotics or placebo plus antibiotics in approximately a 3 to 1 ratio.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Staphylococcus Aureus Bacteremia
Keywords
Staph, antibody
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
52 (Actual)
8. Arms, Groups, and Interventions
Arm Title
514G3
Arm Type
Experimental
Arm Description
Phase I of the study will include a single dose of 514G3 at three different dose levels. Phase II utilizes a single dose of 514G3 at the highest dose level. Standard antibiotic therapies will be used in both phases.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Both Phase I and II will include a single dose of placebo in addition to standard antibiotic therapies.
Intervention Type
Biological
Intervention Name(s)
514G3
Intervention Description
True Human Monoclonal Antibody
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Buffered saline solution
Intervention Type
Drug
Intervention Name(s)
Standard IV antibiotic therapy
Intervention Description
standard antibiotic therapy will be determined by the attending physician and will be guided by the results of cultures with sensitivities.
Primary Outcome Measure Information:
Title
Phase I: Determination of the Maximum Tolerated Dose
Description
The highest dose administered with no more than one dose limiting toxicity
Time Frame
14 Days
Title
Phase II: Safety and tolerability
Description
The incidence of adverse events, serious adverse events, and laboratory abnormalities will be compared between the 514G3 arm and the placebo arm.
Time Frame
28 days
Secondary Outcome Measure Information:
Title
Determination of the serum half-life of 514G3
Description
Serum levels of 514G3 will be measured at protocol specified timepoints to determine the half-life, and to ensure clearance of the antibody during the follow up period after dosing.
Time Frame
28 days
Title
Duration of Fever
Time Frame
28 days
Title
Length of hospitalization
Time Frame
28 days
Title
Time to sterile culture from date of randomization
Description
The time to sterile culture is the interval in days from the first dose of study drug until 2 consecutive days of negative blood cultures has occurred. The difference in this interval will be compared between patients randomized to placebo and those who received the highest dose of 514G3
Time Frame
28 Days
Title
Incidence of Serious Adverse Events
Description
Differences in the incidence of SAEs between the 514G3 and placebo arms will be compared.
Time Frame
28 days
Title
Opsonophagocytosis Assay
Description
Serum samples from patients will be assessed with an in vitro opsonophagocytosis assay which measures the ability of the serum to mediate uptake of staph aureus by white blood cells. Differences in the levels of activity will be compared between treatment and placebo
Time Frame
14 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
One or more blood cultures positive for staphylococcus aureus within 2 days of initiating treatment with 514G3.
Temperature ≥ 38.0°C
Age ≥18, male or female subjects.
Adequate renal function, defined by serum creatinine ≤ 2 times the upper limit of normal (ULN).
Adequate hepatic function
Adequate bone marrow function
For women of childbearing potential (WOCBP), a negative serum pregnancy test result at Screening.
Signed and dated institutional review board (IRB)/ Ethics Committee (EC)-approved informed consent before any protocol-specific screening procedures are performed.
Expected survival of at least 2 months.
Exclusion Criteria:
Polymicrobial bacteremia.
Known or suspected osteomyelitis or meningitis.
Patients that are being mechanically ventilated as a result of a pulmonary infection at the time of screening. Mechanical ventilation for other reasons, such as trauma, is acceptable.
Presence of any removable infection source (e.g., intravascular line, abscess, or prosthesis) that will not be removed or debrided within 3 days after randomization.
Definite or possible left-sided endocarditis, by Modified Duke Criteria, based on screening echocardiogram. Subjects with suspected right-sided endocarditis are permitted.
Need for emergent valve surgery at the time of screening, and/or the presence of decompensated heart failure or cardiogenic shock.
Dementia or altered mental status that would prohibit the understanding or rendering of informed consent.
Infection with human immunodeficiency virus (HIV) and a CD4 count <200 cells/mm3.
Subjects with history of hypersensitivity to compounds of similar chemical or biologic composition to 514G3 or any component of its formulations.
Women who are pregnant or breastfeeding.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mark Rupp, M.D.
Organizational Affiliation
University of Nebraska
Official's Role
Study Chair
Facility Information:
Facility Name
XBiotech Investigative Site
City
Columbus
State/Province
Georgia
ZIP/Postal Code
31904
Country
United States
Facility Name
XBiotech Investigative Site
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28203
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Study of the Safety and Efficacy of 514G3 in Subjects Hospitalized With Bacteremia Due to Staphylococcus Aureus
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