To evaluate the safety and tolerability of raxibacumab in healthy subjects.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
322
40 mg/kg intravenously, double dose (day 0 and 14), Group 3
40 mg/kg intravenously, double dose (day 0 and 14), Group 1
40 mg/kg placebo, single dose (day 0), Group 4
Number of Participants With Any Adverse Event (AE) or Any Serious Adverse Event (SAE) During the Treatment Period
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.
Time frame: 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 With Hematological Toxicities of the Indicated Grade
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.
Time frame: 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 With at Least a 2-grade Worsening From Baseline in Hematological Toxicities
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.
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40 mg/kg intravenously, single dose, day 0, Group 2
Time frame: 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 With Liver Toxicities of the Indicated Grade
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.
Time frame: 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 With at Least a 2-grade Worsening From Baseline in Liver Toxicities
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.
Time frame: 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 With Electrolyte Toxicities of the Indicated Grade
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.
Time frame: 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 With at Least a 2-grade Worsening From Baseline in Electrolyte Toxicities
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.
Time frame: 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 With Other Chemistry Toxicities of the Indicated Grade
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.
Time frame: 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 With at Least a 2-grade Worsening From Baseline in Other Chemistry Toxicities
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.
Time frame: 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 With Thyroid Toxicities of the Indicated Grade
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.
Time frame: 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 With Urinalysis Toxicities of the Indicated Grade
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.
Time frame: 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 With at Least a 2-grade Worsening From Baseline in Urinalysis Toxicities
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.
Time frame: 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
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.
Time frame: From the day of the first dose of study agent (Day 0) until Day 56 (single-dose) or until Day 70 (double-dose)
Mean Raxibacumab Concentration-time Following a Single IV Infusion Dose
Blood was collected from each participant at selected times post dose, and serum specimens were analyzed for raxibacumab using a validated electrochemiluminescense-based assay. The individual serum raxibacumab concentration data were summarized by nominal collection time and treatment group using descriptive statistics. Blood samples for serum raxibacumab concentration measurement were collected from participants who received a single-dose prior to administration of the raxibacumab and diphenhydramine doses on Day 0, at 30 minutes and 2 to 6 hours after completion of the raxibacumab infusion, and at 14, 28, and 56 days after the raxibacumab dose.
Time frame: 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
Mean Raxibacumab Concentration-time Following Two IV Infusion Doses
Blood was collected from each participant at selected times post dose, and serum specimens were analyzed for raxibacumab using a validated electrochemiluminescense-based assay. The individual serum raxibacumab concentration data were summarized by nominal collection time and treatment group using descriptive statistics. For the participants that received two doses, blood samples for serum raxibacumab concentration measurement were collected from participants prior to administration of the raxibacumab and diphenhydramine doses 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.
Time frame: 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