Clinical trial NCT02357966: Safety & Efficacy of True Human Antibody, 514G3, in Staphylococcus Aureus Bacteremia Hospitalized Subjects.
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Staphylococcus Aureus Bacteremia
Keywords: Staphylococcus Aureus, Bacteremia, Hospitalization, Antibody
Lead sponsor: XBiotech, Inc.
Sponsor class: INDUSTRY
First posted: 2015-02-06
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: 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 purpose: TREATMENT

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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants Who Experienced Dose-limiting Toxicities
timeFrame: Pre-dose at Day 0 through Day 14. After day 14, samples are collected every other day including discharge, up to 30 days maximum
measure: Number of Participants Who Experienced the Adverse Events
timeFrame: Adverse events occurring between day 0 and day 30 or hospital discharge whichever is shorter
Secondary outcomes:
measure: Time to Clearance of Bacteremia (Time to Sterile Culture From Date of Randomization)
timeFrame: Pre-dose at Day 0 through Day 14. After day 14, samples are collected every other day including discharge, up to 30 days maximum
measure: Steady State Maximum Concentration of 514G3
timeFrame: Pre-dose at Day 0 through Day 14. After day 14, samples are collected every other day including discharge, up to 30 days maximum
measure: Length of Hospitalization (Duration of Hospitalization Stay After Randomization)
timeFrame: Pre-dose at Day 0 through Day 14. After day 14, samples are collected every other day including discharge, up to 30 days maximum
measure: Difference in Opsonophagocytosis Activity Between Arms (Pharmacodynamics)
timeFrame: 14 days
Other outcomes:
Locations:
city: Columbus
country: United States
facility: XBiotech Investigative Site
state: Georgia
city: Charlotte
country: United States
facility: XBiotech Investigative Site
state: North Carolina
Study officials:
affiliation: University of Nebraska
name: Mark Rupp, M.D.
role: STUDY_CHAIR
References: