- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01263691
Safety, Tolerability and Immunogenicity Study of AV7909 Anthrax Vaccine in Healthy Adults
A Parallel-arm, Double-blind, Randomized, Placebo-controlled, Dose-ranging Clinical Trial Evaluating the Safety, Tolerability and Immunogenicity of AV7909 in Healthy Adults
Study Overview
Status
Conditions
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Florida
-
Miami, Florida, United States, 33143
- Miami Research Associates
-
-
North Carolina
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Raleigh, North Carolina, United States, 27607
- North Carolina Clinical Research
-
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Utah
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Salt Lake City, Utah, United States, 84124
- Jean Brown Research
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: BioThrax
BioThrax, 0.5 mL AVA per dose
|
BioThrax
Other Names:
|
Experimental: AV7909 Formulation 1
0.5 mL AVA + 0.5 mg CPG 7909 per 0.5 mL dose
|
AV7909 Formulation 1
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Experimental: AV7909 Formulation 2
0.5 mL AVA + 0.25 mg CPG 7909 per 0.5 mL dose
|
AV7909 Formulation 2
|
Experimental: AV7909 Formulation 3
0.25 mL AVA + 0.5 mg CPG 7909 per 0.5 mL dose
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AV7909 Formulation 3
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Experimental: AV7909 Formulation 4
0.25 mL AVA + 0.25 mg CPG 7909 per 0.5 mL dose
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AV7909 Formulation 4
|
Placebo Comparator: Control
Saline control
|
Saline control
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of Injection Site Reactions From Subject Diary Cards by Injection and Severity (Mild, Moderate or Severe) Following the First Vaccination (Day 0)
Time Frame: Days 0-6
|
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:
For all other ISRs, the following scale was used:
|
Days 0-6
|
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)
Time Frame: Days 0-6
|
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:
For all other ISRs, the following scale was used:
|
Days 0-6
|
Incidence of Injection Site Reactions From Subject Diary Cards by Injection and Severity (Mild, Moderate or Severe) Following the Second Vaccination (Day 14)
Time Frame: Days 14-20
|
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:
For all other ISRs, the following scale was used:
|
Days 14-20
|
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)
Time Frame: Days 14-20
|
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:
For all other ISRs, the following scale was used:
|
Days 14-20
|
Incidence of Systemic Reactions From Subject Diary Cards by Injection and Severity (Mild, Moderate or Severe) Following the First Injection (Day 0)
Time Frame: Days 0-6
|
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:
For all other systemic reactions, the following scale was used:
|
Days 0-6
|
Percentage of Subjects With Systemic Reactions From Subject Diary Cards by Injection and Severity (Mild, Moderate or Severe) Following the First Injection (Day 0)
Time Frame: Days 0-6
|
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:
For all other systemic reactions, the following scale was used:
|
Days 0-6
|
Incidence of Systemic Reactions From Subject Diary Cards by Injection and Severity (Mild, Moderate or Severe) Following the Second Injection (Day 14)
Time Frame: Days 14-20
|
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:
For all other systemic reactions, the following scale was used:
|
Days 14-20
|
Percentage of Subjects With Systemic Reactions From Subject Diary Cards by Injection and Severity (Mild, Moderate or Severe) Following the Second Injection (Day 14)
Time Frame: Days 14-20
|
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:
For all other systemic reactions, the following scale was used:
|
Days 14-20
|
Incidence of Hematology, Serum Chemistry, and Urinalysis Abnormalities Reported as Adverse Events
Time Frame: Days 0-56
|
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. |
Days 0-56
|
Percentage of Subjects With Hematology, Serum Chemistry, and Urinalysis Abnormalities Reported as Adverse Events
Time Frame: Days 0-56
|
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. |
Days 0-56
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
Time Frame: Day 0 (pre-dose), 7, 14 (pre-dose), 21, 28, 35, 42, 56, 70, and 84.
|
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.
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Day 0 (pre-dose), 7, 14 (pre-dose), 21, 28, 35, 42, 56, 70, and 84.
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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.
Time Frame: Day 0 (pre-dose), 7, 14 (pre-dose), 21, 28, 35, 42, 56, 70, and 84.
|
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.
|
Day 0 (pre-dose), 7, 14 (pre-dose), 21, 28, 35, 42, 56, 70, and 84.
|
TNA NF50 GMTs Across Study Days After IM Administration of Investigational Product on Days 0 and 14.
Time Frame: Day 0 (pre-dose), 7, 14 (pre-dose), 21, 28, 35, 42, 56, 70, and 84.
|
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.
|
Day 0 (pre-dose), 7, 14 (pre-dose), 21, 28, 35, 42, 56, 70, and 84.
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Director: Edward Bernton, MD, Emergent Biosolutions, Inc.
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- EBS.AVA.201 / DMID 10-0013
- HHSN272200800051C (Other Grant/Funding Number: BARDA/NIAID)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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