A Study to Evaluate the Safety and Tolerability of Raxibacumab in Healthy Subjects

Study Overview
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Brief Summary
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To evaluate the safety and tolerability of raxibacumab in healthy subjects.

Official Title
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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

Conditions
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Healthy

Intervention / Treatment
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* Drug: placebo
* Drug: raxibacumab
* Drug: placebo
* Drug: raxibacumab


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: 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) Key Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: raxibacumab<br>* 40 mg/kg intravenously, double dose (day 0 and 14), Group 1<br>|
| Experimental: 2<br> | Drug: raxibacumab<br>* 40 mg/kg intravenously, single dose, day 0, Group 2<br>|
| Placebo Comparator: 3<br> | Drug: placebo<br>* 40 mg/kg intravenously, double dose (day 0 and 14), Group 3<br>|
| Placebo Comparator: 4<br> | Drug: placebo<br>* 40 mg/kg placebo, single dose (day 0), Group 4<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | From the day of the first dose of study agent (Day 0) until Day 56 (single-dose) or until Day 70 (double-dose) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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healthy volunteers