A Study of the Safety and Efficacy of 514G3 in Subjects Hospitalized With Bacteremia Due to Staphylococcus Aureus

Staphylococcus Aureus Bacteremia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02357966
• Other study ID #: 2014-PT029
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: January 29, 2015
• Last updated: February 22, 2017
• Start date: May 2015
• Est. completion date: February 2017

Study information

• Verified date: February 2017
• Source: XBiotech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: February 2017
• Est. primary completion date: January 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. One or more blood cultures positive for staphylococcus aureus within 2 days of initiating treatment with 514G3.

2. Temperature = 38.0°C

3. Age =18, male or female subjects.

4. Adequate renal function, defined by serum creatinine = 2 times the upper limit of normal (ULN).

5. Adequate hepatic function

6. Adequate bone marrow function

7. For women of childbearing potential (WOCBP), a negative serum pregnancy test result at Screening.

8. Signed and dated institutional review board (IRB)/ Ethics Committee (EC)-approved informed consent before any protocol-specific screening procedures are performed.

9. Expected survival of at least 2 months.

Exclusion Criteria:

1. Polymicrobial bacteremia.

2. Known or suspected osteomyelitis or meningitis.

3. 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.

4. 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.

5. Definite or possible left-sided endocarditis, by Modified Duke Criteria, based on screening echocardiogram. Subjects with suspected right-sided endocarditis are permitted.

6. Need for emergent valve surgery at the time of screening, and/or the presence of decompensated heart failure or cardiogenic shock.

7. Dementia or altered mental status that would prohibit the understanding or rendering of informed consent.

8. Infection with human immunodeficiency virus (HIV) and a CD4 count <200 cells/mm3.

9. Subjects with history of hypersensitivity to compounds of similar chemical or biologic composition to 514G3 or any component of its formulations.

10. Women who are pregnant or breastfeeding.

Related Conditions & MeSH terms

• Bacteremia
• Staphylococcus Aureus Bacteremia

Intervention

Biological:
• 514G3
True Human Monoclonal Antibody

Drug:
• Placebo
Buffered saline solution
• Standard IV antibiotic therapy
standard antibiotic therapy will be determined by the attending physician and will be guided by the results of cultures with sensitivities.

Locations

Country	Name	City	State
United States	XBiotech Investigative Site	Charlotte	North Carolina
United States	XBiotech Investigative Site	Columbus	Georgia

Sponsors (1)

Lead Sponsor	Collaborator
XBiotech, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase I: Determination of the Maximum Tolerated Dose	The highest dose administered with no more than one dose limiting toxicity	14 Days
Primary	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.	28 days
Secondary	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.	28 days
Secondary	Duration of Fever		28 days
Secondary	Length of hospitalization		28 days
Secondary	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	28 Days
Secondary	Incidence of Serious Adverse Events	Differences in the incidence of SAEs between the 514G3 and placebo arms will be compared.	28 days
Secondary	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	14 days