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

NCT ID: NCT02357966

Last Updated: 2024-11-21

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

52 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-05-31

Study Completion Date

2016-12-31

Brief Summary

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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.

Detailed Description

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The Phase I/II trial aims to assess the safety and efficacy of True Human monoclonal antibody 514G3 in hospitalized subjects with Staphylococcus aureus bacteremia.

Phase I entails dose escalation, with subjects randomized (3:1) at three dose levels of the study drug (2 mg/kg, 10 mg/kg, and 40 mg/kg) and placebo, utilizing central randomization. Dose-limiting toxicities (DLTs), defined as Grade 3 or greater adverse events related to 514G3 during follow-up, guide escalation. The Maximum Tolerated Dose (MTD) is determined based on DLT occurrence.

Phase II, focusing on preliminary efficacy, randomizes eligible subjects (2:1) to receive 514G3 or placebo with standard IV antibiotic therapy. Safety and efficacy assessments are conducted for both phases, encompassing pooled data from both the study drug and placebo groups.

Conditions

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Staphylococcus Aureus Bacteremia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Phase I

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.

Group Type EXPERIMENTAL

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

Intervention Type BIOLOGICAL

True Human Monoclonal Antibody

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

Intervention Type BIOLOGICAL

True Human Monoclonal Antibody

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

Intervention Type BIOLOGICAL

True Human Monoclonal Antibody

Placebo plus standard IV antibiotic treatment

Intervention Type OTHER

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

Phase II

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.

Group Type EXPERIMENTAL

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

Intervention Type BIOLOGICAL

A single dose of 514G3 plus standard IV antibiotic therapy

Placebo plus standard IV antibiotic treatment: Phase II

Intervention Type OTHER

A single dose of placebo plus standard IV antibiotic therapy

Interventions

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

True Human Monoclonal Antibody

Intervention Type BIOLOGICAL

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

True Human Monoclonal Antibody

Intervention Type BIOLOGICAL

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

True Human Monoclonal Antibody

Intervention Type BIOLOGICAL

Placebo plus standard IV antibiotic treatment

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

Intervention Type OTHER

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

A single dose of 514G3 plus standard IV antibiotic therapy

Intervention Type BIOLOGICAL

Placebo plus standard IV antibiotic treatment: Phase II

A single dose of placebo plus standard IV antibiotic therapy

Intervention Type OTHER

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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XBiotech, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Mark Rupp, M.D.

Role: STUDY_CHAIR

University of Nebraska

Locations

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XBiotech Investigative Site

Columbus, Georgia, United States

Site Status

XBiotech Investigative Site

Charlotte, North Carolina, United States

Site Status

Countries

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United States

Other Identifiers

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2014-PT029

Identifier Type: -

Identifier Source: org_study_id

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