Back to resultsSafety, Tolerability and Immunogenicity Study of AV7909 Anthrax Vaccine in Healthy Adults
Primary Purpose
Bacillus Anthracis (Anthrax) Infection
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
BioThrax
AV7909 Formulation 1
AV7909 Formulation 2
AV7909 Formulation 3
AV7909 Formulation 4
Control
Sponsored by
About this trial
This is an interventional prevention trial for Bacillus Anthracis (Anthrax) Infection focused on measuring AVA, AV7909, Anthrax vaccine
Eligibility Criteria
Inclusion Criteria:
- Be between 18 and 50 years of age, inclusive, at the time of enrollment.
- Be in good health as determined by the investigator from medical history and a physical examination.
- If a pre-menopausal female, must be using acceptable methods of birth control.
- Have all hematology and chemistry parameters (measured at Screening) within the laboratory's normal range.
- Have negative values for the following tests at Screening: Hepatitis C antibody, anti-Human Immunodeficiency Virus (Anti-HIV-1/-2/-O), and anti-Hepatitis B Core Antigen (Anti-HBc).
- Be willing and capable of complying with all aspects of the protocol through completion of the required visits.
- Have not donated blood in the preceding 8 weeks and are willing to not donate blood or plasma within 56 days after dosing.
- Have adequate venous access for repeat phlebotomies.
- Have read, understood and signed an informed consent form.
Exclusion Criteria:
Key Exclusion Criteria:
- A known anaphylactic response, severe systematic response, or serious hypersensitivity reaction to a prior immunization.
- Prior immunization with anthrax vaccine, recombinant Protective Antigen (rPA) vaccine, or known exposure to anthrax organisms.
- Have previously served in the military or plans to enlist in the military from Screening through Day 84.
- Have participated in anthrax therapeutic or vaccine trials (monoclonal anti-protective antigen (PA) or anthrax immune globulins or anthrax vaccines).
- Participation in any investigational clinical trial within 30 days preceding the Screening visit or planning to participate in a clinical trial requiring dosing through the Day 194 visit.
- A history of drug or alcohol abuse within 12 months prior to Screening, or a positive result on a urine drug screen for amphetamines, barbiturates, benzodiazepines, cocaine, marijuana, methylenedioxymethamphetamine opiates, oxycodone, phencyclidine, propoxyphene, or tricyclic antidepressants.
- Blood pressure greater than 145 millimeters of mercury (mmHg) systolic or 90 mmHg diastolic.
- Past history of significant autoimmune disease such as rheumatoid arthritis, lupus erythematous, psoriasis, glomerulonephritis, or autoimmune thyroiditis.
- A medical condition that, in the opinion of the Principal Investigator (PI), could adversely impact the subject's participation, safety, or conduct of the study.
Sites / Locations
- Miami Research Associates
- North Carolina Clinical Research
- Jean Brown Research
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm Type
Active Comparator
Experimental
Experimental
Experimental
Experimental
Placebo Comparator
Arm Label
BioThrax
AV7909 Formulation 1
AV7909 Formulation 2
AV7909 Formulation 3
AV7909 Formulation 4
Control
Arm Description
BioThrax, 0.5 mL AVA per dose
0.5 mL AVA + 0.5 mg CPG 7909 per 0.5 mL dose
0.5 mL AVA + 0.25 mg CPG 7909 per 0.5 mL dose
0.25 mL AVA + 0.5 mg CPG 7909 per 0.5 mL dose
0.25 mL AVA + 0.25 mg CPG 7909 per 0.5 mL dose
Saline control
Outcomes
Primary Outcome Measures
Incidence of Injection Site Reactions From Subject Diary Cards by Injection and Severity (Mild, Moderate or Severe) Following the First Vaccination (Day 0)
Subjects recorded solicited injection site reactions (ISRs) (redness, swelling, tenderness, pain, itching, arm motion limitation) on diary cards for 7 days following the first injection (Day 0).
All local reactions collected by subjects on diary cards were recorded as adverse events.
Severity of ISR was assessed using a grading scale based on FDA Guidance "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials."
Swelling/edema and redness/erythema were graded by the greater of two perpendicular measurements of diameter rated as follows:
Grade 0: none
Grade 1: <3 cm
Grade 2: 3 to 10 cm
Grade 3: >10 cm
For all other ISRs, the following scale was used:
Grade 0: not present
Grade 1: present with no limitation of activity
Grade 2: interfering with daily activities or requiring non-narcotic treatment
Grade 3: preventing normal daily activities or requiring narcotic analgesia
Percentage of Subjects With Injection Site Reactions From Subject Diary Cards by Injection and Severity (Mild, Moderate or Severe) Following the First Vaccination (Day 0)
Subjects recorded solicited injection site reactions (ISRs) (redness, swelling, tenderness, pain, itching, arm motion limitation) on diary cards for 7 days following the first injection (Day 0).
All local reactions collected by subjects on diary cards were recorded as adverse events.
Severity of ISR was assessed using a grading scale based on FDA Guidance "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials."
Swelling/edema and redness/erythema were graded by the greater of two perpendicular measurements of diameter rated as follows:
Grade 0: none
Grade 1: <3 cm
Grade 2: 3 to 10 cm
Grade 3: >10 cm
For all other ISRs, the following scale was used:
Grade 0: not present
Grade 1: present with no limitation of activity
Grade 2: interfering with daily activities or requiring non-narcotic treatment
Grade 3: preventing normal daily activities or requiring narcotic analgesia
Incidence of Injection Site Reactions From Subject Diary Cards by Injection and Severity (Mild, Moderate or Severe) Following the Second Vaccination (Day 14)
Subjects recorded solicited injection site reactions (ISRs) (redness, swelling, tenderness, pain, itching, arm motion limitation) on diary cards for 7 days following the second injection (Day 14).
All local reactions collected by subjects on diary cards were recorded as adverse events.
Severity of ISR was assessed using a grading scale based on FDA Guidance "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials."
Swelling/edema and redness/erythema were graded by the greater of two perpendicular measurements of diameter rated as follows:
Grade 0: none
Grade 1: <3 cm
Grade 2: 3 to 10 cm
Grade 3: >10 cm
For all other ISRs, the following scale was used:
Grade 0: not present
Grade 1: present with no limitation of activity
Grade 2: interfering with daily activities or requiring non-narcotic treatment
Grade 3: preventing normal daily activities or requiring narcotic analgesia
Percentage of Subjects With Injection Site Reactions From Subject Diary Cards by Injection and Severity (Mild, Moderate or Severe) Following the Second Vaccination (Day 14)
Subjects recorded solicited injection site reactions (ISRs) (redness, swelling, tenderness, pain, itching, arm motion limitation) on diary cards for 7 days following the second injection (Day 14).
All local reactions collected by subjects on diary cards were recorded as adverse events.
Severity of ISR was assessed using a grading scale based on FDA Guidance "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials."
Swelling/edema and redness/erythema were graded by the greater of two perpendicular measurements of diameter rated as follows:
Grade 0: none
Grade 1: <3 cm
Grade 2: 3 to 10 cm
Grade 3: >10 cm
For all other ISRs, the following scale was used:
Grade 0: not present
Grade 1: present with no limitation of activity
Grade 2: interfering with daily activities or requiring non-narcotic treatment
Grade 3: preventing normal daily activities or requiring narcotic analgesia
Incidence of Systemic Reactions From Subject Diary Cards by Injection and Severity (Mild, Moderate or Severe) Following the First Injection (Day 0)
Subjects recorded solicited systemic reactions (fever, fatigue, muscle aching, headache, nausea/GI upset) on diary cards for 7 days following each of two injections (Days 0 and 14) All systemic reactions collected by subjects on diary cards were recorded as adverse events.
Severity of systemic reactions was assessed using a grading scale based on FDA Guidance titled "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials."
Toxicity grades for fever were derived from body temperature using the following scale:
Grade 0: <100°F
Grade 1: 100.0 - 101.5°F
Grade 2: 101.6 - 102.9°F ;
Grade 3: 103.0 - 105.0°F
For all other systemic reactions, the following scale was used:
Grade 0: not present
Grade 1: present with no limitation of activity
Grade 2: interfering with daily activities or requiring non-narcotic treatment
Grade 3: preventing normal daily activities or requiring narcotic analgesia
Percentage of Subjects With Systemic Reactions From Subject Diary Cards by Injection and Severity (Mild, Moderate or Severe) Following the First Injection (Day 0)
Subjects recorded solicited systemic reactions (fever, fatigue, muscle aching, headache, nausea/GI upset) on diary cards for 7 days following each of two injections (Days 0 and 14) All systemic reactions collected by subjects on diary cards were recorded as adverse events.
Severity of systemic reactions was assessed using a grading scale based on FDA Guidance titled "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials."
Toxicity grades for fever were derived from body temperature using the following scale:
Grade 0: <100°F
Grade 1: 100.0 - 101.5°F
Grade 2: 101.6 - 102.9°F ;
Grade 3: 103.0 - 105.0°F
For all other systemic reactions, the following scale was used:
Grade 0: not present
Grade 1: present with no limitation of activity
Grade 2: interfering with daily activities or requiring non-narcotic treatment
Grade 3: preventing normal daily activities or requiring narcotic analgesia
Incidence of Systemic Reactions From Subject Diary Cards by Injection and Severity (Mild, Moderate or Severe) Following the Second Injection (Day 14)
Subjects recorded solicited systemic reactions (fever, fatigue, muscle aching, headache, nausea/GI upset) on diary cards for 7 days following each of two injections (Days 0 and 14) All systemic reactions collected by subjects on diary cards were recorded as adverse events.
Severity of systemic reactions was assessed using a grading scale based on FDA Guidance titled "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials."
Toxicity grades for fever were derived from body temperature using the following scale:
Grade 0: <100°F
Grade 1: 100.0 - 101.5°F
Grade 2: 101.6 - 102.9°F ;
Grade 3: 103.0 - 105.0°F
For all other systemic reactions, the following scale was used:
Grade 0: not present
Grade 1: present with no limitation of activity
Grade 2: interfering with daily activities or requiring non-narcotic treatment
Grade 3: preventing normal daily activities or requiring narcotic analgesia
Percentage of Subjects With Systemic Reactions From Subject Diary Cards by Injection and Severity (Mild, Moderate or Severe) Following the Second Injection (Day 14)
Subjects recorded solicited systemic reactions (fever, fatigue, muscle aching, headache, nausea/GI upset) on diary cards for 7 days following each of two injections (Days 0 and 14) All systemic reactions collected by subjects on diary cards were recorded as adverse events.
Severity of systemic reactions was assessed using a grading scale based on FDA Guidance titled "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials."
Toxicity grades for fever were derived from body temperature using the following scale:
Grade 0: <100°F
Grade 1: 100.0 - 101.5°F
Grade 2: 101.6 - 102.9°F ;
Grade 3: 103.0 - 105.0°F
For all other systemic reactions, the following scale was used:
Grade 0: not present
Grade 1: present with no limitation of activity
Grade 2: interfering with daily activities or requiring non-narcotic treatment
Grade 3: preventing normal daily activities or requiring narcotic analgesia
Incidence of Hematology, Serum Chemistry, and Urinalysis Abnormalities Reported as Adverse Events
Hematology test included hemoglobin, hematocrit, white blood cell count, absolute lymphocyte count, absolute neutrophil count, absolute eosinophil count, and platelet count. Serum chemistry test included albumin, alkaline phosphatase, total bilirubin, blood urea nitrogen, creatinine, glucose, calcium, potassium, alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase. Urinalysis included appearance, color, pH, specific gravity, ketones, protein, glucose, bilirubin, nitrite, urobilinogen, and occult blood.
Hematology tests were done on Days 0, 1, 2, 7, 28, and 56. Serum chemistry tests and urinalysis were done on Days 0, 7, 28, and 56.
Percentage of Subjects With Hematology, Serum Chemistry, and Urinalysis Abnormalities Reported as Adverse Events
Hematology test included hemoglobin, hematocrit, white blood cell count, absolute lymphocyte count, absolute neutrophil count, absolute eosinophil count, and platelet count. Serum chemistry test included albumin, alkaline phosphatase, total bilirubin, blood urea nitrogen, creatinine, glucose, calcium, potassium, alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase. Urinalysis included appearance, color, pH, specific gravity, ketones, protein, glucose, bilirubin, nitrite, urobilinogen, and occult blood.
Hematology tests were done on Days 0, 1, 2, 7, 28, and 56. Serum chemistry tests and urinalysis were done on Days 0, 7, 28, and 56.
Secondary Outcome Measures
Peak TNA NF50 GMT for All Subjects in the Immunogenicity Population and by Gender After IM Administration of Investigational Product on Days 0 and 14.
Toxin neutralizing antibody (TNA) levels in blinded serum samples were measured using a validated anthrax lethal toxin neutralization assay. The primary assay endpoint was the 50% neutralization factor (TNA NF50). TNA NF50 is calculated as the ratio of the 50% effective dose (ED50) of the test sample to the ED50 of a reference serum. Values below the lower limit of quantitation (LLOQ) of the assay (ED50 of 33) were replaced with one-half the LLOQ (ED50 of 16.5) for calculation of geometric mean titer (GMT) and statistical analysis. GMT is based on log transformation.
Median Time to Peak TNA NF50 GMT for All Subjects in the Immunogenicity Population and by Gender After IM Administration of Investigational Product on Days 0 and 14.
Toxin neutralizing antibody (TNA) levels in blinded serum samples were measured using a validated anthrax lethal toxin neutralization assay. The primary assay endpoint was the 50% neutralization factor (TNA NF50). TNA NF50 is calculated as the ratio of the 50% effective dose (ED50) of the test sample to the ED50 of a reference serum. Values below the LLOQ of the assay (ED50 of 33) were replaced with one-half the LLOQ (ED50 of 16.5) for calculation of geometric mean titer (GMT) and statistical analysis. GMT is based on log transformation.
TNA NF50 GMTs Across Study Days After IM Administration of Investigational Product on Days 0 and 14.
Toxin neutralizing antibody (TNA) levels in blinded serum samples were measured using a validated anthrax lethal toxin neutralization assay. The primary assay endpoint was the 50% neutralization factor (TNA NF50). TNA NF50 is calculated as the ratio of the 50% effective dose (ED50) of the test sample to the ED50 of a reference serum. Values below the LLOQ of the assay (ED50 of 33) were replaced with one-half the LLOQ (ED50 of 16.5) for calculation of geometric mean titer (GMT) and statistical analysis. GMT is based on log transformation.
Full Information
NCT ID
NCT01263691
First Posted
December 17, 2010
Last Updated
August 1, 2014
Sponsor
Emergent BioSolutions
Collaborators
National Institute of Allergy and Infectious Diseases (NIAID), Department of Health and Human Services
1. Study Identification
Unique Protocol Identification Number
NCT01263691
Brief Title
Safety, Tolerability and Immunogenicity Study of AV7909 Anthrax Vaccine in Healthy Adults
Official Title
A Parallel-arm, Double-blind, Randomized, Placebo-controlled, Dose-ranging Clinical Trial Evaluating the Safety, Tolerability and Immunogenicity of AV7909 in Healthy Adults
Study Type
Interventional
2. Study Status
Record Verification Date
August 2014
Overall Recruitment Status
Completed
Study Start Date
December 2010 (undefined)
Primary Completion Date
May 2012 (Actual)
Study Completion Date
June 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Emergent BioSolutions
Collaborators
National Institute of Allergy and Infectious Diseases (NIAID), Department of Health and Human Services
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this Phase 1 clinical trial is to evaluate the safety, tolerability, and immunogenicity of AV7909 anthrax vaccine in healthy adults. In this study, healthy male and female subjects between 18 and 50 years of age will receive vaccinations via the intramuscular (IM) route at Days 0 and 14. Safety and tolerability will be evaluated via laboratory tests, physical examinations, vital signs, adverse events (AEs), concomitant medications, and local and systemic signs and symptoms of reactogenicity.
Detailed Description
AV7909 is a new vaccine which is a combination of BioThrax (also called anthrax vaccine, adsorbed or AVA), a FDA-licensed vaccine, and CPG 7909. CPG 7909 is a synthetic short DNA sequence that has been shown to be an effective vaccine adjuvant, and one which increases the speed and the degree of the immune response to Protective Antigen (PA), the major vaccine antigen. In the current study, the safety, tolerability, and antibody response to PA will be studied for four different combinations of AVA and CPG 7909, and compared to both AVA and a saline placebo. All formulations of AV7909 have the same or less AVA than the licensed AVA vaccine and all have less CPG 7909 per dose than the formulation used in the first Phase I volunteer study of CPG 7909 combined with AVA.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bacillus Anthracis (Anthrax) Infection
Keywords
AVA, AV7909, Anthrax vaccine
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
105 (Actual)
8. Arms, Groups, and Interventions
Arm Title
BioThrax
Arm Type
Active Comparator
Arm Description
BioThrax, 0.5 mL AVA per dose
Arm Title
AV7909 Formulation 1
Arm Type
Experimental
Arm Description
0.5 mL AVA + 0.5 mg CPG 7909 per 0.5 mL dose
Arm Title
AV7909 Formulation 2
Arm Type
Experimental
Arm Description
0.5 mL AVA + 0.25 mg CPG 7909 per 0.5 mL dose
Arm Title
AV7909 Formulation 3
Arm Type
Experimental
Arm Description
0.25 mL AVA + 0.5 mg CPG 7909 per 0.5 mL dose
Arm Title
AV7909 Formulation 4
Arm Type
Experimental
Arm Description
0.25 mL AVA + 0.25 mg CPG 7909 per 0.5 mL dose
Arm Title
Control
Arm Type
Placebo Comparator
Arm Description
Saline control
Intervention Type
Biological
Intervention Name(s)
BioThrax
Other Intervention Name(s)
Anthrax Vaccine Adsorbed (AVA)
Intervention Description
BioThrax
Intervention Type
Biological
Intervention Name(s)
AV7909 Formulation 1
Intervention Description
AV7909 Formulation 1
Intervention Type
Biological
Intervention Name(s)
AV7909 Formulation 2
Intervention Description
AV7909 Formulation 2
Intervention Type
Biological
Intervention Name(s)
AV7909 Formulation 3
Intervention Description
AV7909 Formulation 3
Intervention Type
Biological
Intervention Name(s)
AV7909 Formulation 4
Intervention Description
AV7909 Formulation 4
Intervention Type
Drug
Intervention Name(s)
Control
Intervention Description
Saline control
Primary Outcome Measure Information:
Title
Incidence of Injection Site Reactions From Subject Diary Cards by Injection and Severity (Mild, Moderate or Severe) Following the First Vaccination (Day 0)
Description
Subjects recorded solicited injection site reactions (ISRs) (redness, swelling, tenderness, pain, itching, arm motion limitation) on diary cards for 7 days following the first injection (Day 0).
All local reactions collected by subjects on diary cards were recorded as adverse events.
Severity of ISR was assessed using a grading scale based on FDA Guidance "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials."
Swelling/edema and redness/erythema were graded by the greater of two perpendicular measurements of diameter rated as follows:
Grade 0: none
Grade 1: <3 cm
Grade 2: 3 to 10 cm
Grade 3: >10 cm
For all other ISRs, the following scale was used:
Grade 0: not present
Grade 1: present with no limitation of activity
Grade 2: interfering with daily activities or requiring non-narcotic treatment
Grade 3: preventing normal daily activities or requiring narcotic analgesia
Time Frame
Days 0-6
Title
Percentage of Subjects With Injection Site Reactions From Subject Diary Cards by Injection and Severity (Mild, Moderate or Severe) Following the First Vaccination (Day 0)
Description
Subjects recorded solicited injection site reactions (ISRs) (redness, swelling, tenderness, pain, itching, arm motion limitation) on diary cards for 7 days following the first injection (Day 0).
All local reactions collected by subjects on diary cards were recorded as adverse events.
Severity of ISR was assessed using a grading scale based on FDA Guidance "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials."
Swelling/edema and redness/erythema were graded by the greater of two perpendicular measurements of diameter rated as follows:
Grade 0: none
Grade 1: <3 cm
Grade 2: 3 to 10 cm
Grade 3: >10 cm
For all other ISRs, the following scale was used:
Grade 0: not present
Grade 1: present with no limitation of activity
Grade 2: interfering with daily activities or requiring non-narcotic treatment
Grade 3: preventing normal daily activities or requiring narcotic analgesia
Time Frame
Days 0-6
Title
Incidence of Injection Site Reactions From Subject Diary Cards by Injection and Severity (Mild, Moderate or Severe) Following the Second Vaccination (Day 14)
Description
Subjects recorded solicited injection site reactions (ISRs) (redness, swelling, tenderness, pain, itching, arm motion limitation) on diary cards for 7 days following the second injection (Day 14).
All local reactions collected by subjects on diary cards were recorded as adverse events.
Severity of ISR was assessed using a grading scale based on FDA Guidance "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials."
Swelling/edema and redness/erythema were graded by the greater of two perpendicular measurements of diameter rated as follows:
Grade 0: none
Grade 1: <3 cm
Grade 2: 3 to 10 cm
Grade 3: >10 cm
For all other ISRs, the following scale was used:
Grade 0: not present
Grade 1: present with no limitation of activity
Grade 2: interfering with daily activities or requiring non-narcotic treatment
Grade 3: preventing normal daily activities or requiring narcotic analgesia
Time Frame
Days 14-20
Title
Percentage of Subjects With Injection Site Reactions From Subject Diary Cards by Injection and Severity (Mild, Moderate or Severe) Following the Second Vaccination (Day 14)
Description
Subjects recorded solicited injection site reactions (ISRs) (redness, swelling, tenderness, pain, itching, arm motion limitation) on diary cards for 7 days following the second injection (Day 14).
All local reactions collected by subjects on diary cards were recorded as adverse events.
Severity of ISR was assessed using a grading scale based on FDA Guidance "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials."
Swelling/edema and redness/erythema were graded by the greater of two perpendicular measurements of diameter rated as follows:
Grade 0: none
Grade 1: <3 cm
Grade 2: 3 to 10 cm
Grade 3: >10 cm
For all other ISRs, the following scale was used:
Grade 0: not present
Grade 1: present with no limitation of activity
Grade 2: interfering with daily activities or requiring non-narcotic treatment
Grade 3: preventing normal daily activities or requiring narcotic analgesia
Time Frame
Days 14-20
Title
Incidence of Systemic Reactions From Subject Diary Cards by Injection and Severity (Mild, Moderate or Severe) Following the First Injection (Day 0)
Description
Subjects recorded solicited systemic reactions (fever, fatigue, muscle aching, headache, nausea/GI upset) on diary cards for 7 days following each of two injections (Days 0 and 14) All systemic reactions collected by subjects on diary cards were recorded as adverse events.
Severity of systemic reactions was assessed using a grading scale based on FDA Guidance titled "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials."
Toxicity grades for fever were derived from body temperature using the following scale:
Grade 0: <100°F
Grade 1: 100.0 - 101.5°F
Grade 2: 101.6 - 102.9°F ;
Grade 3: 103.0 - 105.0°F
For all other systemic reactions, the following scale was used:
Grade 0: not present
Grade 1: present with no limitation of activity
Grade 2: interfering with daily activities or requiring non-narcotic treatment
Grade 3: preventing normal daily activities or requiring narcotic analgesia
Time Frame
Days 0-6
Title
Percentage of Subjects With Systemic Reactions From Subject Diary Cards by Injection and Severity (Mild, Moderate or Severe) Following the First Injection (Day 0)
Description
Subjects recorded solicited systemic reactions (fever, fatigue, muscle aching, headache, nausea/GI upset) on diary cards for 7 days following each of two injections (Days 0 and 14) All systemic reactions collected by subjects on diary cards were recorded as adverse events.
Severity of systemic reactions was assessed using a grading scale based on FDA Guidance titled "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials."
Toxicity grades for fever were derived from body temperature using the following scale:
Grade 0: <100°F
Grade 1: 100.0 - 101.5°F
Grade 2: 101.6 - 102.9°F ;
Grade 3: 103.0 - 105.0°F
For all other systemic reactions, the following scale was used:
Grade 0: not present
Grade 1: present with no limitation of activity
Grade 2: interfering with daily activities or requiring non-narcotic treatment
Grade 3: preventing normal daily activities or requiring narcotic analgesia
Time Frame
Days 0-6
Title
Incidence of Systemic Reactions From Subject Diary Cards by Injection and Severity (Mild, Moderate or Severe) Following the Second Injection (Day 14)
Description
Subjects recorded solicited systemic reactions (fever, fatigue, muscle aching, headache, nausea/GI upset) on diary cards for 7 days following each of two injections (Days 0 and 14) All systemic reactions collected by subjects on diary cards were recorded as adverse events.
Severity of systemic reactions was assessed using a grading scale based on FDA Guidance titled "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials."
Toxicity grades for fever were derived from body temperature using the following scale:
Grade 0: <100°F
Grade 1: 100.0 - 101.5°F
Grade 2: 101.6 - 102.9°F ;
Grade 3: 103.0 - 105.0°F
For all other systemic reactions, the following scale was used:
Grade 0: not present
Grade 1: present with no limitation of activity
Grade 2: interfering with daily activities or requiring non-narcotic treatment
Grade 3: preventing normal daily activities or requiring narcotic analgesia
Time Frame
Days 14-20
Title
Percentage of Subjects With Systemic Reactions From Subject Diary Cards by Injection and Severity (Mild, Moderate or Severe) Following the Second Injection (Day 14)
Description
Subjects recorded solicited systemic reactions (fever, fatigue, muscle aching, headache, nausea/GI upset) on diary cards for 7 days following each of two injections (Days 0 and 14) All systemic reactions collected by subjects on diary cards were recorded as adverse events.
Severity of systemic reactions was assessed using a grading scale based on FDA Guidance titled "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials."
Toxicity grades for fever were derived from body temperature using the following scale:
Grade 0: <100°F
Grade 1: 100.0 - 101.5°F
Grade 2: 101.6 - 102.9°F ;
Grade 3: 103.0 - 105.0°F
For all other systemic reactions, the following scale was used:
Grade 0: not present
Grade 1: present with no limitation of activity
Grade 2: interfering with daily activities or requiring non-narcotic treatment
Grade 3: preventing normal daily activities or requiring narcotic analgesia
Time Frame
Days 14-20
Title
Incidence of Hematology, Serum Chemistry, and Urinalysis Abnormalities Reported as Adverse Events
Description
Hematology test included hemoglobin, hematocrit, white blood cell count, absolute lymphocyte count, absolute neutrophil count, absolute eosinophil count, and platelet count. Serum chemistry test included albumin, alkaline phosphatase, total bilirubin, blood urea nitrogen, creatinine, glucose, calcium, potassium, alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase. Urinalysis included appearance, color, pH, specific gravity, ketones, protein, glucose, bilirubin, nitrite, urobilinogen, and occult blood.
Hematology tests were done on Days 0, 1, 2, 7, 28, and 56. Serum chemistry tests and urinalysis were done on Days 0, 7, 28, and 56.
Time Frame
Days 0-56
Title
Percentage of Subjects With Hematology, Serum Chemistry, and Urinalysis Abnormalities Reported as Adverse Events
Description
Hematology test included hemoglobin, hematocrit, white blood cell count, absolute lymphocyte count, absolute neutrophil count, absolute eosinophil count, and platelet count. Serum chemistry test included albumin, alkaline phosphatase, total bilirubin, blood urea nitrogen, creatinine, glucose, calcium, potassium, alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase. Urinalysis included appearance, color, pH, specific gravity, ketones, protein, glucose, bilirubin, nitrite, urobilinogen, and occult blood.
Hematology tests were done on Days 0, 1, 2, 7, 28, and 56. Serum chemistry tests and urinalysis were done on Days 0, 7, 28, and 56.
Time Frame
Days 0-56
Secondary Outcome Measure Information:
Title
Peak TNA NF50 GMT for All Subjects in the Immunogenicity Population and by Gender After IM Administration of Investigational Product on Days 0 and 14.
Description
Toxin neutralizing antibody (TNA) levels in blinded serum samples were measured using a validated anthrax lethal toxin neutralization assay. The primary assay endpoint was the 50% neutralization factor (TNA NF50). TNA NF50 is calculated as the ratio of the 50% effective dose (ED50) of the test sample to the ED50 of a reference serum. Values below the lower limit of quantitation (LLOQ) of the assay (ED50 of 33) were replaced with one-half the LLOQ (ED50 of 16.5) for calculation of geometric mean titer (GMT) and statistical analysis. GMT is based on log transformation.
Time Frame
Day 0 (pre-dose), 7, 14 (pre-dose), 21, 28, 35, 42, 56, 70, and 84.
Title
Median Time to Peak TNA NF50 GMT for All Subjects in the Immunogenicity Population and by Gender After IM Administration of Investigational Product on Days 0 and 14.
Description
Toxin neutralizing antibody (TNA) levels in blinded serum samples were measured using a validated anthrax lethal toxin neutralization assay. The primary assay endpoint was the 50% neutralization factor (TNA NF50). TNA NF50 is calculated as the ratio of the 50% effective dose (ED50) of the test sample to the ED50 of a reference serum. Values below the LLOQ of the assay (ED50 of 33) were replaced with one-half the LLOQ (ED50 of 16.5) for calculation of geometric mean titer (GMT) and statistical analysis. GMT is based on log transformation.
Time Frame
Day 0 (pre-dose), 7, 14 (pre-dose), 21, 28, 35, 42, 56, 70, and 84.
Title
TNA NF50 GMTs Across Study Days After IM Administration of Investigational Product on Days 0 and 14.
Description
Toxin neutralizing antibody (TNA) levels in blinded serum samples were measured using a validated anthrax lethal toxin neutralization assay. The primary assay endpoint was the 50% neutralization factor (TNA NF50). TNA NF50 is calculated as the ratio of the 50% effective dose (ED50) of the test sample to the ED50 of a reference serum. Values below the LLOQ of the assay (ED50 of 33) were replaced with one-half the LLOQ (ED50 of 16.5) for calculation of geometric mean titer (GMT) and statistical analysis. GMT is based on log transformation.
Time Frame
Day 0 (pre-dose), 7, 14 (pre-dose), 21, 28, 35, 42, 56, 70, and 84.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Be between 18 and 50 years of age, inclusive, at the time of enrollment.
Be in good health as determined by the investigator from medical history and a physical examination.
If a pre-menopausal female, must be using acceptable methods of birth control.
Have all hematology and chemistry parameters (measured at Screening) within the laboratory's normal range.
Have negative values for the following tests at Screening: Hepatitis C antibody, anti-Human Immunodeficiency Virus (Anti-HIV-1/-2/-O), and anti-Hepatitis B Core Antigen (Anti-HBc).
Be willing and capable of complying with all aspects of the protocol through completion of the required visits.
Have not donated blood in the preceding 8 weeks and are willing to not donate blood or plasma within 56 days after dosing.
Have adequate venous access for repeat phlebotomies.
Have read, understood and signed an informed consent form.
Exclusion Criteria:
Key Exclusion Criteria:
A known anaphylactic response, severe systematic response, or serious hypersensitivity reaction to a prior immunization.
Prior immunization with anthrax vaccine, recombinant Protective Antigen (rPA) vaccine, or known exposure to anthrax organisms.
Have previously served in the military or plans to enlist in the military from Screening through Day 84.
Have participated in anthrax therapeutic or vaccine trials (monoclonal anti-protective antigen (PA) or anthrax immune globulins or anthrax vaccines).
Participation in any investigational clinical trial within 30 days preceding the Screening visit or planning to participate in a clinical trial requiring dosing through the Day 194 visit.
A history of drug or alcohol abuse within 12 months prior to Screening, or a positive result on a urine drug screen for amphetamines, barbiturates, benzodiazepines, cocaine, marijuana, methylenedioxymethamphetamine opiates, oxycodone, phencyclidine, propoxyphene, or tricyclic antidepressants.
Blood pressure greater than 145 millimeters of mercury (mmHg) systolic or 90 mmHg diastolic.
Past history of significant autoimmune disease such as rheumatoid arthritis, lupus erythematous, psoriasis, glomerulonephritis, or autoimmune thyroiditis.
A medical condition that, in the opinion of the Principal Investigator (PI), could adversely impact the subject's participation, safety, or conduct of the study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Edward Bernton, MD
Organizational Affiliation
Emergent Biosolutions, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Miami Research Associates
City
Miami
State/Province
Florida
ZIP/Postal Code
33143
Country
United States
Facility Name
North Carolina Clinical Research
City
Raleigh
State/Province
North Carolina
ZIP/Postal Code
27607
Country
United States
Facility Name
Jean Brown Research
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84124
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
23701746
Citation
Hopkins RJ, Daczkowski NF, Kaptur PE, Muse D, Sheldon E, LaForce C, Sari S, Rudge TL, Bernton E. Randomized, double-blind, placebo-controlled, safety and immunogenicity study of 4 formulations of Anthrax Vaccine Adsorbed plus CPG 7909 (AV7909) in healthy adult volunteers. Vaccine. 2013 Jun 26;31(30):3051-8. doi: 10.1016/j.vaccine.2013.04.063. Epub 2013 May 10.
Results Reference
result
Learn more about this trial
Safety, Tolerability and Immunogenicity Study of AV7909 Anthrax Vaccine in Healthy Adults
We'll reach out to this number within 24 hrs