A Randomized, Single-blind, Placebo-controlled Study to Evaluate the Safety and Tolerability of Raxibacumab (Human Monoclonal Antibody to B. Anthracis Protective Antigen) in Healthy Subjects
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 322
- 主要终点
- Number of Participants With Hematological Toxicities of the Indicated Grade
研究概览
简要总结
To evaluate the safety and tolerability of raxibacumab in healthy subjects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (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
- 是
入选标准
- •Male or female, 18 years of age or older
- •Normal laboratory (blood test) results
- •Subjects are eligible to enter the study if they are not pregnant or nursing, are sterile or of non-childbearing potential, or are willing to practice abstinence or use appropriate birth control methods during the study (about 2 months)
排除标准
- •History of significant, acute or chronic diseases (ie, heart, lung, gastrointestinal, liver, kidney, neurological or infectious diseases).
- •Prior immunization with anthrax vaccine adsorbed (AVA), prior treatment with investigational anthrax therapies, prior treatment for anthrax exposure, or prior anthrax infection.
- •History of Type I hypersensitivity reaction to food or drugs, IV contrast agents, antihistamines, or history of hives.
- •A current drug or alcohol addiction.
- •Positive for human immunodeficiency virus (HIV-1), Hepatitis B surface antigen, or Hepatitis C antibody.
- •Cancer within the last 5 years (with the exception of adequately treated basal cell carcinoma of the skin or in situ carcinoma of the cervix).
- •Participation within 60 days of intiating study or refusal to refrain from participation during the study in any other clinical trials of an investigational compound.
- •Previous exposure to raxibacumab.
研究组 & 干预措施
1
干预措施: raxibacumab (Drug)
2
干预措施: raxibacumab (Drug)
3
干预措施: placebo (Drug)
4
干预措施: placebo (Drug)
结局指标
主要结局
Number of Participants With Hematological Toxicities of the Indicated Grade
时间窗: From the day of the first dose of study agent (Day 0) until Day 56 (single-dose) or until Day 70 (double-dose)
Clinical hematological parameters were assessed using the modified Division of Microbiology and Infectious Diseases (DMID) toxicity tables, version 2.0. Grade 1 (Mild): Transient or mild discomfort (\< 48 hours); no medical intervention or therapy required. Grade 2 (Moderate): Mild to moderate limitation in activity, some assistance may be needed; no or minimal medical intervention or therapy required. Grade 3 (Severe): Marked limitation in activity, some assistance usually required; medical intervention or therapy required, hospitalizations possible. Grade 4 (Life-threatening): Extreme limitation in activity, significant assistance required; significant medical intervention or therapy required, hospitalization or hospice care probable.
Number of Participants With at Least a 2-grade Worsening From Baseline in Other Chemistry Toxicities
时间窗: From the day of the first dose of study agent (Day 0) until Day 56 (single-dose) or until Day 70 (double-dose)
The number of participants with at least a 2-grade worsening from Baseline in other chemistry toxicities were assessed. Other clinical chemistry parameters were assessed using the modified Division of Microbiology and Infectious Diseases (DMID) toxicity tables, version 2.0. Grade 1 (Mild): Transient or mild discomfort (\< 48 hours); no medical intervention or therapy required. Grade 2 (Moderate): Mild to moderate limitation in activity, some assistance may be needed; no or minimal medical intervention or therapy required. Grade 3 (Severe): Marked limitation in activity, some assistance usually required; medical intervention or therapy required, hospitalizations possible. Grade 4 (Life-threatening): Extreme limitation in activity, significant assistance required; significant medical intervention or therapy required, hospitalization or hospice care probable. Baseline is defined as the value of the variable measured at Day 0 prior to dosing.
Number of Participants With Any Adverse Event (AE) or Any Serious Adverse Event (SAE) During the Treatment Period
时间窗: From the day of the first dose of study agent (Day 0) until Day 56 (single-dose) or until Day 70 (double-dose)
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. This includes worsening (eg, increase in frequency or severity) of pre-existing conditions. A serious adverse event (SAE) is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect. Medical or scientific judgment should be exercised in deciding whether reporting is appropriate in other situations. Refer to the General Adverse AE/SAE module for a complete list of AEs and SAEs.
Number of Participants With Liver Toxicities of the Indicated Grade
时间窗: From the day of the first dose of study agent (Day 0) until Day 56 (single-dose) or until Day 70 (double-dose)
Liver function parameters were assessed using the modified Division of Microbiology and Infectious Diseases (DMID) toxicity tables, version 2.0. Grade 1 (Mild): Transient or mild discomfort (\< 48 hours); no medical intervention or therapy required. Grade 2 (Moderate): Mild to moderate limitation in activity, some assistance may be needed; no or minimal medical intervention or therapy required. Grade 3 (Severe): Marked limitation in activity, some assistance usually required; medical intervention or therapy required, hospitalizations possible. Grade 4 (Life-threatening): Extreme limitation in activity, significant assistance required; significant medical intervention or therapy required, hospitalization or hospice care probable.
Number of Participants With at Least a 2-grade Worsening From Baseline in Electrolyte Toxicities
时间窗: From the day of the first dose of study agent (Day 0) until Day 56 (single-dose) or until Day 70 (double-dose)
The number of participants with at least a 2-grade worsening from Baseline in electrolyte toxicities were assessed. Electrolyte function parameters were assessed using the modified Division of Microbiology and Infectious Diseases (DMID) toxicity tables, version 2.0. Grade 1 (Mild): Transient or mild discomfort (\< 48 hours); no medical intervention or therapy required. Grade 2 (Moderate): Mild to moderate limitation in activity, some assistance may be needed; no or minimal medical intervention or therapy required. Grade 3 (Severe): Marked limitation in activity, some assistance usually required; medical intervention or therapy required, hospitalizations possible. Grade 4 (Life-threatening): Extreme limitation in activity, significant assistance required; significant medical intervention or therapy required, hospitalization or hospice care probable. Baseline is defined as the value of the variable measured at Day 0 prior to dosing.
Number of Participants With at Least a 2-grade Worsening From Baseline in Hematological Toxicities
时间窗: From the day of the first dose of study agent (Day 0) until Day 56 (single-dose) or until Day 70 (double-dose)
The number of participants with at least a 2-grade worsening from Baseline in hematological toxicities were assessed. Clinical hematological parameters were assessed using the modified Division of Microbiology and Infectious Diseases (DMID) toxicity tables, version 2.0. Grade 1 (Mild): Transient or mild discomfort (\< 48 hours); no medical intervention or therapy required. Grade 2 (Moderate): Mild to moderate limitation in activity, some assistance may be needed; no or minimal medical intervention or therapy required. Grade 3 (Severe): Marked limitation in activity, some assistance usually required; medical intervention or therapy required, hospitalizations possible. Grade 4 (Life-threatening): Extreme limitation in activity, significant assistance required; significant medical intervention or therapy required, hospitalization or hospice care probable. Baseline is defined as the value of the variable measured at Day 0 prior to dosing.
Number of Participants With at Least a 2-grade Worsening From Baseline in Liver Toxicities
时间窗: From the day of the first dose of study agent (Day 0) until Day 56 (single-dose) or until Day 70 (double-dose)
The number of participants with at least a 2-grade worsening from Baseline in liver toxicities were assessed. Liver function parameters were assessed using the modified Division of Microbiology and Infectious Diseases (DMID) toxicity tables, version 2.0. Grade 1 (Mild): Transient or mild discomfort (\< 48 hours); no medical intervention or therapy required. Grade 2 (Moderate): Mild to moderate limitation in activity, some assistance may be needed; no or minimal medical intervention or therapy required. Grade 3 (Severe): Marked limitation in activity, some assistance usually required; medical intervention or therapy required, hospitalizations possible. Grade 4 (Life-threatening): Extreme limitation in activity, significant assistance required; significant medical intervention or therapy required, hospitalization or hospice care probable. Baseline is defined as the value of the variable measured at Day 0 prior to dosing.
Number of Participants With Electrolyte Toxicities of the Indicated Grade
时间窗: From the day of the first dose of study agent (Day 0) until Day 56 (single-dose) or until Day 70 (double-dose)
Electrolyte function parameters were assessed using the modified Division of Microbiology and Infectious Diseases (DMID) toxicity tables, version 2.0. Grade 1 (Mild): Transient or mild discomfort (\< 48 hours); no medical intervention or therapy required. Grade 2 (Moderate): Mild to moderate limitation in activity, some assistance may be needed; no or minimal medical intervention or therapy required. Grade 3 (Severe): Marked limitation in activity, some assistance usually required; medical intervention or therapy required, hospitalizations possible. Grade 4 (Life-threatening): Extreme limitation in activity, significant assistance required; significant medical intervention or therapy required, hospitalization or hospice care probable.
Number of Participants With Other Chemistry Toxicities of the Indicated Grade
时间窗: From the day of the first dose of study agent (Day 0) until Day 56 (single-dose) or until Day 70 (double-dose)
Other chemistry parameters were assessed using the modified Division of Microbiology and Infectious Diseases (DMID) toxicity tables, version 2.0. Grade 1 (Mild): Transient or mild discomfort (\< 48 hours); no medical intervention or therapy required. Grade 2 (Moderate): Mild to moderate limitation in activity, some assistance may be needed; no or minimal medical intervention or therapy required. Grade 3 (Severe): Marked limitation in activity, some assistance usually required; medical intervention or therapy required, hospitalizations possible. Grade 4 (Life-threatening): Extreme limitation in activity, significant assistance required; significant medical intervention or therapy required, hospitalization or hospice care probable.
Number of Participants With Thyroid Toxicities of the Indicated Grade
时间窗: From the day of the first dose of study agent (Day 0) until Day 56 (single-dose) or until Day 70 (double-dose)
Clinical thyroid parameters were assessed using the modified Division of Microbiology and Infectious Diseases (DMID) toxicity tables, version 2.0. Grade 1 (Mild): Transient or mild discomfort (\< 48 hours); no medical intervention or therapy required. Grade 2 (Moderate): Mild to moderate limitation in activity, some assistance may be needed; no or minimal medical intervention or therapy required. Grade 3 (Severe): Marked limitation in activity, some assistance usually required; medical intervention or therapy required, hospitalizations possible. Grade 4 (Life-threatening): Extreme limitation in activity, significant assistance required; significant medical intervention or therapy required, hospitalization or hospice care probable.
Number of Participants With Urinalysis Toxicities of the Indicated Grade
时间窗: From the day of the first dose of study agent (Day 0) until Day 56 (single-dose) or until Day 70 (double-dose)
Urinaysis parameters were assessed using the modified Division of Microbiology and Infectious Diseases (DMID) toxicity tables, version 2.0. Grade 1 (Mild): Transient or mild discomfort (\< 48 hours); no medical intervention or therapy required. Grade 2 (Moderate): Mild to moderate limitation in activity, some assistance may be needed; no or minimal medical intervention or therapy required. Grade 3 (Severe): Marked limitation in activity, some assistance usually required; medical intervention or therapy required, hospitalizations possible. Grade 4 (Life-threatening): Extreme limitation in activity, significant assistance required; significant medical intervention or therapy required, hospitalization or hospice care probable.
Number of Participants Who Developed an Anti-raxibacumab Antibody Response
时间窗: From the day of the first dose of study agent (Day 0) until Day 56 (single-dose) or until Day 70 (double-dose)
Number of participants who developed an anti-raxibacumab antibody response during the study were assessed. .Immunogenicity testing was performed to determine if raxibacumab induced an anti-raxibacumab immune response. Testing comprised of 2 assays (screening and confirmatory). The screening assay (direct binding) was an electrochemiluminescence (ECL)-based bridging assay. A rabbit polyclonal antibody was used as a positive control. Samples above the assay cut point were considered positive. Samples identified as positive in the screening assay were confirmed positive in a confirmatory assay. Samples must have demonstrated a significant percent drop in the confirmatory inhibition of binding assay to be considered positive. The inhibition of binding confirmatory assay was performed identically to the direct binding screening assay with the exception that the samples were tested in parallel with excess unlabeled raxibacumab.
Number of Participants With at Least a 2-grade Worsening From Baseline in Urinalysis Toxicities
时间窗: From the day of the first dose of study agent (Day 0) until Day 56 (single-dose) or until Day 70 (double-dose)
Urinalysis parameters were assessed using the modified Division of Microbiology and Infectious Diseases (DMID) toxicity tables, version 2.0. Grade 1 (Mild): Transient or mild discomfort (\< 48 hours); no medical intervention or therapy required. Grade 2 (Moderate): Mild to moderate limitation in activity, some assistance may be needed; no or minimal medical intervention or therapy required. Grade 3 (Severe): Marked limitation in activity, some assistance usually required; medical intervention or therapy required, hospitalizations possible. Grade 4 (Life-threatening): Extreme limitation in activity, significant assistance required; significant medical intervention or therapy required, hospitalization or hospice care probable. Baseline is defined as the value of the variable measured at Day 0 prior to dosing.
次要结局
- Mean Raxibacumab Concentration-time Following Two IV Infusion Doses(Pre-dose on Days 0 and 14, at 30 minutes and 2 to 6 hours after completion of each raxibacumab infusion, and at 28, 42, 56, and 70 days after the 1st raxibacumab dose)
- Mean Raxibacumab Concentration-time Following a Single IV Infusion Dose(Pre-dose on Day 0, at 30 minutes and 2 to 6 hours after completion of raxibacumab infusion, and at 14, 28, and 56 days after the raxibacumab dose)