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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 52
- 试验地点
- 2
- 主要终点
- Number of Participants Who Experienced Dose-limiting Toxicities
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •One or more blood cultures positive for staphylococcus aureus within 2 days of initiating treatment with 514G
- •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.
排除标准
- •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/mm
- •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.
研究组 & 干预措施
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.
干预措施: 514G3 (2 mg/kg) plus standard IV antibiotic treatment (Biological)
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.
干预措施: 514G3 (10 mg/kg) plus standard IV antibiotic treatment (Biological)
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.
干预措施: 514G3 (40 mg/kg) plus standard IV antibiotic treatment (Biological)
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.
干预措施: Placebo plus standard IV antibiotic treatment (Other)
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.
干预措施: 514G3 (40 mg/kg) plus standard IV antibiotic treatment: Phase II (Biological)
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.
干预措施: Placebo plus standard IV antibiotic treatment: Phase II (Other)
结局指标
主要结局
Number of Participants Who Experienced Dose-limiting Toxicities
时间窗: Pre-dose at Day 0 through Day 14. After day 14, samples are collected every other day including discharge, up to 30 days maximum
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.
Number of Participants Who Experienced the Adverse Events
时间窗: Adverse events occurring between day 0 and day 30 or hospital discharge whichever is shorter
A summary of SAEs and other non-serious AEs, regardless of causality
次要结局
- 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)