Safety & Efficacy of True Human Antibody, 514G3, in Staphylococcus Aureus Bacteremia Hospitalized Subjects.

NCT02357966 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 2014-PT029
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 2

Brief Summary

This study is a Phase I/II, double-blind, placebo-controlled trial investigating the True Human monoclonal antibody 514G3 in subjects hospitalized with Staphylococcus aureus bacteremia. Phase I involves dose escalation to evaluate potential toxicity and establish the recommended phase 2 dosage of 514G3. In Phase II (dose expansion), eligible subjects will be randomized at a ratio of 2:1 to receive either a single dose of 514G3 with standard IV antibiotic therapy or a single dose of placebo with standard IV antibiotic therapy, aiming to assess safety and tolerability. The trial aims to determine the safety, efficacy, and optimal dosage regimen of 514G3 in these hospitalized subjects.

Conditions

Staphylococcus Aureus Bacteremia

Keywords

Staphylococcus Aureus, Bacteremia, Hospitalization, Antibody

Outcome Measures

Primary Outcomes (2)

• Number of Participants Who Experienced Dose-limiting Toxicities

  Dose limiting Toxicity are defined as any Grade 3 or greater AE which is probably or definitely related to 514G3 occurring during the FU period after dosing. This measure determines and assesses the maximum tolerated dose (MTD) through participants who experienced DLT at different dose levels.

  Pre-dose at Day 0 through Day 14. After day 14, samples are collected every other day including discharge, up to 30 days maximum

• Number of Participants Who Experienced the Adverse Events

  A summary of SAEs and other non-serious AEs, regardless of causality

  Adverse events occurring between day 0 and day 30 or hospital discharge whichever is shorter

Secondary Outcomes (4)

• Time to Clearance of Bacteremia (Time to Sterile Culture From Date of Randomization)

  Pre-dose at Day 0 through Day 14. After day 14, samples are collected every other day including discharge, up to 30 days maximum

• Steady State Maximum Concentration of 514G3

  Pre-dose at Day 0 through Day 14. After day 14, samples are collected every other day including discharge, up to 30 days maximum

• Length of Hospitalization (Duration of Hospitalization Stay After Randomization)

  Pre-dose at Day 0 through Day 14. After day 14, samples are collected every other day including discharge, up to 30 days maximum

• Difference in Opsonophagocytosis Activity Between Arms (Pharmacodynamics)

  14 days

Study Arms (2)

Phase I

EXPERIMENTAL

A phase I of the trial is a dose escalation study intended to assess the possible toxicity and to determine the recommended phase 2 dose (RP2D) of the study drug (514G3). Randomized subjects were administered the study drug at 3 dose levels i.e. 2 mg/kg, 10 mg/kg, and 40 mg/kg or placebo.

Biological: 514G3 (2 mg/kg) plus standard IV antibiotic treatment; Biological: 514G3 (10 mg/kg) plus standard IV antibiotic treatment; Biological: 514G3 (40 mg/kg) plus standard IV antibiotic treatment; Other: Placebo plus standard IV antibiotic treatment

Phase II

EXPERIMENTAL

A phase 2 of the trial is a dose expansion study designed to assess the preliminary efficacy. Eligible subjects are randomized (2:1) and received a single dose of 40 mg/kg study drug (514G3) with standard IV treatment versus placebo with standard IV treatment.

Biological: 514G3 (40 mg/kg) plus standard IV antibiotic treatment: Phase II; Other: Placebo plus standard IV antibiotic treatment: Phase II

Interventions

514G3 (2 mg/kg) plus standard IV antibiotic treatment BIOLOGICAL

Also known as: True Human Monoclonal Antibody

Phase I

514G3 (10 mg/kg) plus standard IV antibiotic treatment BIOLOGICAL

Also known as: True Human Monoclonal Antibody

Phase I

514G3 (40 mg/kg) plus standard IV antibiotic treatment BIOLOGICAL

Also known as: True Human Monoclonal Antibody

Phase I

Placebo plus standard IV antibiotic treatment OTHER

Sterile isotonic formulation buffered at pH 6.2 - 6.5 plus standard IV antibiotic treatment

Also known as: True Human Monoclonal Antibody

Phase I

514G3 (40 mg/kg) plus standard IV antibiotic treatment: Phase II BIOLOGICAL

A single dose of 514G3 plus standard IV antibiotic therapy

Also known as: True Human Monoclonal Antibody

Phase II

Placebo plus standard IV antibiotic treatment: Phase II OTHER

A single dose of placebo plus standard IV antibiotic therapy

Also known as: True Human Monoclonal Antibody

Phase II

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• XBiotech, Inc.: lead

Study Sites (2)

XBiotech Investigative Site

Columbus, Georgia, 31904, United States

Location

XBiotech Investigative Site

Charlotte, North Carolina, 28203, United States

Location

MeSH Terms

Conditions

Staphylococcal Infections; Bacteremia

Condition Hierarchy (Ancestors)

Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Haritha Pallapotu
• Organization: XBiotech USA, Inc.

hpallapotu@xbiotech.com

512-386-2992

Study Officials

• Mark Rupp, M.D.

  University of Nebraska

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a Phase I/II, double blind placebo controlled trial of the True Human monoclonal antibody 514G3 in subjects hospitalized with Staphylococcus Aureus bacteremia. A phase I of the trial is a dose escalation study intended to assess the possible toxicity and to determine the recommended phase 2 dose of the study drug (514G3). Eligible subjects will be randomized (3:1) to receive single dose of 514G3 (Either 2, 10, 40 mg/kg) plus standard IV antibiotic therapy or single dose of placebo plus standard IV antibiotic therapy. A phase 2 of the trial is designed to assess the preliminary efficacy through randomization of subjects in two arm groups i.e. a single dose of 514G3 administered at the RP2D with standard IV treatment or placebo plus standard IV treatment. Eligible subjects will be randomized (2:1) to receive either a single dose of 514G3 plus standard IV antibiotic therapy versus a single dose of placebo plus standard IV antibiotic treatment.

Study Record Dates

• First Submitted: January 29, 2015
• First Posted: February 6, 2015
• Study Start: May 1, 2015
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: February 9, 2026
• Results First Posted: November 21, 2024

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)