Back to resultsA Phase 2 Safety and Immunogenicity Study for an Anthrax Vaccine Using 3 Schedules and Two Dose Levels
Primary Purpose
Anthrax
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
AV7909
BioThrax
Sponsored by
About this trial
This is an interventional prevention trial for Anthrax focused on measuring post-exposure prophylaxis, toxin neutralization assay
Eligibility Criteria
Inclusion Criteria:
- Be 18-50 years old
- Be in good health
- Have access to a computer and the internet so you can complete a diary
- Agree to abstain from sex the first 84 days of the study or practice birth control if you are a woman who is able to get pregnant
- Have not donated blood for the previous 8 weeks
Exclusion Criteria:
- A known anaphylactic response, severe systemic response, or serious hypersensitivity reaction to a prior immunization.
- A history of latex allergy.
- Have received a shot (vaccine), including flu shots, in the past 6 weeks or plan to get a shot for 4 weeks after the last study shot is given.
- Have previously served in the military any time after 1990 or plan to enlist in the military from Screening through Day 84.
- Prior immunization with anthrax vaccine, recombinant protective antigen (rPA) vaccine, or known exposure to anthrax organisms.
- Have participated in anthrax therapeutic or vaccine studies (monoclonal anti-PA or anthrax immune globulins or anthrax vaccines).
- Participation in any investigational study involving use of a pharmacological intervention within 30 days before the Screening visit or planning to participate in a study requiring dosing through the 12-month safety follow-up telephone call.
- Have a known diagnosis of any immunodeficiency disease including but not limited to: acquired immune deficiency syndrome (AIDS), common variable immunodeficiency disease, immunoglobulin A (IgA) deficiency, or hypogammaglobulinemia.
- Past history of significant autoimmune disease such as rheumatoid arthritis, lupus erythematous, psoriasis in the area of vaccinations, or requires immunotherapy, glomerulonephritis, or autoimmune thyroiditis.
- Have received immunosuppressive therapy with cytotoxic drugs or Rituximab within the past 2 years.
- A history of cytotoxic chemotherapy or radiation therapy.
- Chronic (>10 days) daily oral or parenteral corticosteroid therapy in the past 12 months.
- Any lung disease, including reactive airway disease, which requires the daily use of medications.
- A female currently breastfeeding or with a positive pregnancy test.
- A history of drug or alcohol abuse within 12 months prior to Screening, or a positive result on a urine drug screen for cocaine, marijuana, opiates, methamphetamines, benzodiazepines, or oxycodone.
- Any tattoo or other skin condition in the deltoid region on either arm that may obscure the assessment of the injection sites.
- A medical condition that, in the opinion of the PI or designee, could adversely impact the subject's participation or safety or the conduct of the study.
- Any planned elective in-patient surgery during the study period.
Sites / Locations
- Miami Research Associates
- Costal Carolina Research
- Central Texas Allergy and Asthma
- Jean Brown Research
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Experimental
Experimental
Experimental
Experimental
Active Comparator
Arm Label
AV7909 (Day 0 and 14)
AV7909 (Day 0 and 28)
AV7909 (Day 0, 14, and 28)
AV7909 Reduced Dose
BioThrax
Arm Description
Route of administration: Intramuscular Dose: 0.5 mL Schedule: Day 0 and Day 14
Route of administration: Intramuscular Dose: 0.5 mL Schedule: Day 0 and Day 28
Route of administration: Intramuscular Dose: 0.5 mL Schedule: Day 0, Day 14,and Day 28
Route of administration: Intramuscular Dose: 0.25 mL Schedule: Day 0, Day 14,and Day 28
Route of administration: Intramuscular Dose: 0.5 mL Schedule: Day 0, Day 14,and Day 28
Outcomes
Primary Outcome Measures
Toxin Neutralizing Antibody (TNA) Level at Day 63
Immunogenicity measured by the lower bound (LB) of the 95% confidence intervals (CIs) for the proportion of subjects in each study arm with Day 63 TNA 50% neutralization factor (NF50) values greater than or equal to threshold
Incidence of Adverse Events
Incidence of adverse events (including assessment of symptoms, physical exam findings, clinical laboratory tests, and vital signs) from the time of the first immunization on Day 0 through Day 84
Incidence of Serious Adverse Events
Incidence of serious adverse events, from the time of the first immunization on Day 0 through the 12-month safety follow-up telephone call following the last scheduled vaccination
Incidence of Reactogenicity By Severity
Incidence of solicited systemic reactions and solicited injection site reactions each day for 7 days following each vaccination using subject e-diaries by severity.
Reactions were graded using the following scale (note, for redness and swelling, the diameter [greater of two perpendicular measurements] was assessed by the subject using an injection site measurement tool):
Grade 0 (Absent): Symptom not present; Grade 1 (Mild): Symptom present but does not interfere with activities of daily living, or affected area (redness, swelling) measures <3 cm; Grade 2 (Moderate): Symptom causes some interference with activities of daily living, or affected area (redness, swelling) measures 3 - 10 cm; Grade 3 (Severe): Symptom prevents activities of daily living or requires treatment, or affected area (redness, swelling) measures > 10 cm.
For each reaction, subjects are counted once across all vaccinations at the highest reported level of severity.
Incidence of Clinical Laborabory Abnormalities
Incidence of clinical laboratory abnormalities throughout the study (up to Day 84).
Clinical laboratory abnormalities are presented as the total of Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), and Grade 4 (potentially life-threatening) abnormalities according to criteria adapted from the U.S. Department of Health and Human Services, Food and Drug Administration, Center for Biologics Evaluation and Research: Guidance for Industry. Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (September 2007). Within each laboratory parameter, subjects are counted once for their most severe occurrence of clinical laboratory abnormality.
Incidence of Immunologically Significant Adverse Events of Special Interest
Incidence of immunologically significant adverse events of special interest as defined by the Center for Biologics Evaluation and Research from the time of the first immunization on Day 0 through the 12-month safety follow-up telephone call following the last scheduled vaccination
Secondary Outcome Measures
TNA Level at Day 42
Immunogenicity measured by the percentage of subjects in each study arm with Day 42 TNA NF50 values greater than or equal to threshold
TNA Level at Day 28
Immunogenicity measured by the percentage of subjects with Day 28 TNA NF50 values greater than or equal to threshold
TNA Seroconversion Rate
Immunogenicity measured by the percentage of subjects who have seroconverted (defined as a 4-fold increase over Day 0 in TNA NF50 value) at Days 21, 28, 35, 42, 49, 63, and 84
Full Information
NCT ID
NCT01770743
First Posted
January 16, 2013
Last Updated
February 6, 2015
Sponsor
Emergent BioSolutions
Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
1. Study Identification
Unique Protocol Identification Number
NCT01770743
Brief Title
A Phase 2 Safety and Immunogenicity Study for an Anthrax Vaccine Using 3 Schedules and Two Dose Levels
Official Title
A Phase 2, Randomized, Parallel-Group, Active-Controlled, Double-Blind Study to Evaluate the Safety and Immunogenicity of AV7909 for Post-Exposure Prophylaxis of Anthrax Using Three Immunization Schedules and Two Dose Levels in Healthy Adult Volunteers
Study Type
Interventional
2. Study Status
Record Verification Date
February 2015
Overall Recruitment Status
Completed
Study Start Date
January 2013 (undefined)
Primary Completion Date
February 2014 (Actual)
Study Completion Date
December 2014 (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)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to assess the safety and immunogenicity of an anthrax vaccine. The vaccine schedule and dose will also be assessed.
Detailed Description
The safety and immunogenicity of AV7909 for post-exposure prophylaxis of anthrax will be evaluated using a randomized, parallel-group, active-controlled, double-blind design with three immunization schedules and two dose levels in healthy adult volunteers. Safety will be assessed by clinical laboratory tests (hematology, serum chemistry, and urinalysis), monitoring of adverse events, vital signs, and physical examinations. Reactogenicity (systemic and injection site reactions) will be assessed by the subjects using subject e-diaries for 7 days after each immunization and by the investigator at in-clinic visits 7 and 14 days after each immunization, and at other visits, if applicable. Immunogenicity will be measured as toxin neutralizing antibody (TNA) response and seroconversion rates.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anthrax
Keywords
post-exposure prophylaxis, toxin neutralization assay
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
168 (Actual)
8. Arms, Groups, and Interventions
Arm Title
AV7909 (Day 0 and 14)
Arm Type
Experimental
Arm Description
Route of administration: Intramuscular Dose: 0.5 mL Schedule: Day 0 and Day 14
Arm Title
AV7909 (Day 0 and 28)
Arm Type
Experimental
Arm Description
Route of administration: Intramuscular Dose: 0.5 mL Schedule: Day 0 and Day 28
Arm Title
AV7909 (Day 0, 14, and 28)
Arm Type
Experimental
Arm Description
Route of administration: Intramuscular Dose: 0.5 mL Schedule: Day 0, Day 14,and Day 28
Arm Title
AV7909 Reduced Dose
Arm Type
Experimental
Arm Description
Route of administration: Intramuscular Dose: 0.25 mL Schedule: Day 0, Day 14,and Day 28
Arm Title
BioThrax
Arm Type
Active Comparator
Arm Description
Route of administration: Intramuscular Dose: 0.5 mL Schedule: Day 0, Day 14,and Day 28
Intervention Type
Biological
Intervention Name(s)
AV7909
Other Intervention Name(s)
AV7909 Anthrax Vaccine, NuThrax
Intervention Description
Anthrax Vaccine Adsorbed plus CPG 7909 Adjuvant
Intervention Type
Biological
Intervention Name(s)
BioThrax
Other Intervention Name(s)
Anthrax Vaccine Adsorbed (AVA)
Primary Outcome Measure Information:
Title
Toxin Neutralizing Antibody (TNA) Level at Day 63
Description
Immunogenicity measured by the lower bound (LB) of the 95% confidence intervals (CIs) for the proportion of subjects in each study arm with Day 63 TNA 50% neutralization factor (NF50) values greater than or equal to threshold
Time Frame
Day 63
Title
Incidence of Adverse Events
Description
Incidence of adverse events (including assessment of symptoms, physical exam findings, clinical laboratory tests, and vital signs) from the time of the first immunization on Day 0 through Day 84
Time Frame
From the time of the first immunization on Day 0 through Day 84
Title
Incidence of Serious Adverse Events
Description
Incidence of serious adverse events, from the time of the first immunization on Day 0 through the 12-month safety follow-up telephone call following the last scheduled vaccination
Time Frame
From the time of the first immunization on Day 0 through the 12-month safety follow-up telephone call following the last scheduled vaccination
Title
Incidence of Reactogenicity By Severity
Description
Incidence of solicited systemic reactions and solicited injection site reactions each day for 7 days following each vaccination using subject e-diaries by severity.
Reactions were graded using the following scale (note, for redness and swelling, the diameter [greater of two perpendicular measurements] was assessed by the subject using an injection site measurement tool):
Grade 0 (Absent): Symptom not present; Grade 1 (Mild): Symptom present but does not interfere with activities of daily living, or affected area (redness, swelling) measures <3 cm; Grade 2 (Moderate): Symptom causes some interference with activities of daily living, or affected area (redness, swelling) measures 3 - 10 cm; Grade 3 (Severe): Symptom prevents activities of daily living or requires treatment, or affected area (redness, swelling) measures > 10 cm.
For each reaction, subjects are counted once across all vaccinations at the highest reported level of severity.
Time Frame
For 7 days following each vaccination on Days 0, 14, 28
Title
Incidence of Clinical Laborabory Abnormalities
Description
Incidence of clinical laboratory abnormalities throughout the study (up to Day 84).
Clinical laboratory abnormalities are presented as the total of Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), and Grade 4 (potentially life-threatening) abnormalities according to criteria adapted from the U.S. Department of Health and Human Services, Food and Drug Administration, Center for Biologics Evaluation and Research: Guidance for Industry. Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (September 2007). Within each laboratory parameter, subjects are counted once for their most severe occurrence of clinical laboratory abnormality.
Time Frame
From the time of first immunization on Day 0 to Day 84
Title
Incidence of Immunologically Significant Adverse Events of Special Interest
Description
Incidence of immunologically significant adverse events of special interest as defined by the Center for Biologics Evaluation and Research from the time of the first immunization on Day 0 through the 12-month safety follow-up telephone call following the last scheduled vaccination
Time Frame
From the time of the first immunization on Day 0 through the 12-month safety follow-up telephone call following the last scheduled vaccination
Secondary Outcome Measure Information:
Title
TNA Level at Day 42
Description
Immunogenicity measured by the percentage of subjects in each study arm with Day 42 TNA NF50 values greater than or equal to threshold
Time Frame
Day 42
Title
TNA Level at Day 28
Description
Immunogenicity measured by the percentage of subjects with Day 28 TNA NF50 values greater than or equal to threshold
Time Frame
Day 28
Title
TNA Seroconversion Rate
Description
Immunogenicity measured by the percentage of subjects who have seroconverted (defined as a 4-fold increase over Day 0 in TNA NF50 value) at Days 21, 28, 35, 42, 49, 63, and 84
Time Frame
Up to Day 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 18-50 years old
Be in good health
Have access to a computer and the internet so you can complete a diary
Agree to abstain from sex the first 84 days of the study or practice birth control if you are a woman who is able to get pregnant
Have not donated blood for the previous 8 weeks
Exclusion Criteria:
A known anaphylactic response, severe systemic response, or serious hypersensitivity reaction to a prior immunization.
A history of latex allergy.
Have received a shot (vaccine), including flu shots, in the past 6 weeks or plan to get a shot for 4 weeks after the last study shot is given.
Have previously served in the military any time after 1990 or plan to enlist in the military from Screening through Day 84.
Prior immunization with anthrax vaccine, recombinant protective antigen (rPA) vaccine, or known exposure to anthrax organisms.
Have participated in anthrax therapeutic or vaccine studies (monoclonal anti-PA or anthrax immune globulins or anthrax vaccines).
Participation in any investigational study involving use of a pharmacological intervention within 30 days before the Screening visit or planning to participate in a study requiring dosing through the 12-month safety follow-up telephone call.
Have a known diagnosis of any immunodeficiency disease including but not limited to: acquired immune deficiency syndrome (AIDS), common variable immunodeficiency disease, immunoglobulin A (IgA) deficiency, or hypogammaglobulinemia.
Past history of significant autoimmune disease such as rheumatoid arthritis, lupus erythematous, psoriasis in the area of vaccinations, or requires immunotherapy, glomerulonephritis, or autoimmune thyroiditis.
Have received immunosuppressive therapy with cytotoxic drugs or Rituximab within the past 2 years.
A history of cytotoxic chemotherapy or radiation therapy.
Chronic (>10 days) daily oral or parenteral corticosteroid therapy in the past 12 months.
Any lung disease, including reactive airway disease, which requires the daily use of medications.
A female currently breastfeeding or with a positive pregnancy test.
A history of drug or alcohol abuse within 12 months prior to Screening, or a positive result on a urine drug screen for cocaine, marijuana, opiates, methamphetamines, benzodiazepines, or oxycodone.
Any tattoo or other skin condition in the deltoid region on either arm that may obscure the assessment of the injection sites.
A medical condition that, in the opinion of the PI or designee, could adversely impact the subject's participation or safety or the conduct of the study.
Any planned elective in-patient surgery during the study period.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gurdyal Kalsi, MD, MTOPRA
Organizational Affiliation
Emergent BioSolutions
Official's Role
Principal Investigator
Facility Information:
Facility Name
Miami Research Associates
City
Miami
State/Province
Florida
ZIP/Postal Code
33143
Country
United States
Facility Name
Costal Carolina Research
City
Mount Pleasant
State/Province
South Carolina
ZIP/Postal Code
29464
Country
United States
Facility Name
Central Texas Allergy and Asthma
City
New Braunfels
State/Province
Texas
ZIP/Postal Code
78130
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
Learn more about this trial
A Phase 2 Safety and Immunogenicity Study for an Anthrax Vaccine Using 3 Schedules and Two Dose Levels
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