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

XBiotech

Status and phase: Completed; Phase 2; Phase 1

Conditions: Staphylococcus Aureus Bacteremia

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT02357966

2014-PT029

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 52 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Double Blind

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52 participants in 2 patient groups

Phase I

Experimental group

Description:

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.

Treatment:

Other: Placebo plus standard IV antibiotic treatment

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

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

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

Phase II

Experimental group

Description:

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.

Treatment:

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

Other: Placebo plus standard IV antibiotic treatment: Phase II