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

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

To evaluate the safety and tolerability of raxibacumab in healthy subjects.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: raxibacumab; Drug: raxibacumab; Drug: placebo; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 322
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Human Genome Sciences Inc.
• Collaborators: GlaxoSmithKline; Emergent BioSolutions

Publications and helpful links

General Publications

• Migone TS, Subramanian GM, Zhong J, Healey LM, Corey A, Devalaraja M, Lo L, Ullrich S, Zimmerman J, Chen A, Lewis M, Meister G, Gillum K, Sanford D, Mott J, Bolmer SD. Raxibacumab for the treatment of inhalational anthrax. N Engl J Med. 2009 Jul 9;361(2):135-44. doi: 10.1056/NEJMoa0810603.

Study record dates

Study Major Dates

• Study Start: March 1, 2008
• Primary Completion (Actual): July 1, 2008
• Study Completion (Actual): September 1, 2008

Study Registration Dates

• First Submitted: March 13, 2008
• First Submitted That Met QC Criteria: March 19, 2008
• First Posted (Estimate): March 20, 2008

Study Record Updates

• Last Update Posted (Actual): November 15, 2018
• Last Update Submitted That Met QC Criteria: November 13, 2018
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Keywords: healthy volunteers
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Immunologic Factors; Antibodies, Monoclonal
• Other Study ID Numbers: HGS1021-C1063