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

Overview

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

Full Title of Study: “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”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Single (Investigator)
  • Study Primary Completion Date: July 2008

Interventions

  • Drug: placebo
    • 40 mg/kg intravenously, double dose (day 0 and 14), Group 3
  • Drug: raxibacumab
    • 40 mg/kg intravenously, double dose (day 0 and 14), Group 1
  • Drug: placebo
    • 40 mg/kg placebo, single dose (day 0), Group 4
  • Drug: raxibacumab
    • 40 mg/kg intravenously, single dose, day 0, Group 2

Arms, Groups and Cohorts

  • Experimental: 1
  • Experimental: 2
  • Placebo Comparator: 3
  • Placebo Comparator: 4

Clinical Trial Outcome Measures

Primary Measures

  • Number of Participants With Any Adverse Event (AE) or Any Serious Adverse Event (SAE) During the Treatment Period
    • 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)
    • 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 Hematological Toxicities of the Indicated Grade
    • 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)
    • 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 Hematological Toxicities
    • 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)
    • 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 Liver Toxicities of the Indicated Grade
    • 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)
    • 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 Liver Toxicities
    • 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)
    • 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
    • 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)
    • 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 at Least a 2-grade Worsening From Baseline in Electrolyte Toxicities
    • 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)
    • 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 Other Chemistry Toxicities of the Indicated Grade
    • 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)
    • 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 at Least a 2-grade Worsening From Baseline in Other Chemistry Toxicities
    • 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)
    • 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 Thyroid Toxicities of the Indicated Grade
    • 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)
    • 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
    • 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)
    • 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 With at Least a 2-grade Worsening From Baseline in Urinalysis Toxicities
    • 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)
    • 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.
  • Number of Participants Who Developed an Anti-raxibacumab Antibody Response
    • 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 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.

Secondary Measures

  • Mean Raxibacumab Concentration-time Following a Single IV Infusion 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
    • 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.
  • Mean Raxibacumab Concentration-time Following Two IV Infusion Doses
    • 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
    • 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.

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • Human Genome Sciences Inc.
  • Collaborator
    • GlaxoSmithKline
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • GSK Clinical Trials, Study Director, GlaxoSmithKline

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.