- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02357966
A Study of the Safety and Efficacy of 514G3 in Subjects Hospitalized With Bacteremia Due to Staphylococcus Aureus
February 22, 2017 updated by: XBiotech, Inc.
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
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
52
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
-
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Georgia
-
Columbus, Georgia, United States, 31904
- XBiotech Investigative Site
-
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North Carolina
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Charlotte, North Carolina, United States, 28203
- XBiotech Investigative Site
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-
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 and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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.
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 Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 514G3
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.
|
True Human Monoclonal Antibody
standard antibiotic therapy will be determined by the attending physician and will be guided by the results of cultures with sensitivities.
|
Placebo Comparator: Placebo
Both Phase I and II will include a single dose of placebo in addition to standard antibiotic therapies.
|
Buffered saline solution
standard antibiotic therapy will be determined by the attending physician and will be guided by the results of cultures with sensitivities.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Phase I: Determination of the Maximum Tolerated Dose
Time Frame: 14 Days
|
The highest dose administered with no more than one dose limiting toxicity
|
14 Days
|
Phase II: Safety and tolerability
Time Frame: 28 days
|
The incidence of adverse events, serious adverse events, and laboratory abnormalities will be compared between the 514G3 arm and the placebo arm.
|
28 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Determination of the serum half-life of 514G3
Time Frame: 28 days
|
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.
|
28 days
|
Duration of Fever
Time Frame: 28 days
|
28 days
|
|
Length of hospitalization
Time Frame: 28 days
|
28 days
|
|
Time to sterile culture from date of randomization
Time Frame: 28 Days
|
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
|
28 Days
|
Incidence of Serious Adverse Events
Time Frame: 28 days
|
Differences in the incidence of SAEs between the 514G3 and placebo arms will be compared.
|
28 days
|
Opsonophagocytosis Assay
Time Frame: 14 days
|
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
|
14 days
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Chair: Mark Rupp, M.D., University of Nebraska
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 (Actual)
May 1, 2015
Primary Completion (Actual)
January 1, 2017
Study Completion (Actual)
February 1, 2017
Study Registration Dates
First Submitted
January 29, 2015
First Submitted That Met QC Criteria
February 2, 2015
First Posted (Estimate)
February 6, 2015
Study Record Updates
Last Update Posted (Actual)
February 24, 2017
Last Update Submitted That Met QC Criteria
February 22, 2017
Last Verified
February 1, 2017
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2014-PT029
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
No
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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-
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