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A Phase 2 Safety and Immunogenicity Study for an Anthrax Vaccine Using 3 Schedules and Two Dose Levels

Sponsor
Emergent BioSolutions (Industry)
Overall Status
Completed
CT.gov ID
NCT01770743
Collaborator
National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
168
Enrollment
4
Locations
5
Arms
23
Duration (Months)
42
Patients Per Site
1.8
Patients Per Site Per Month

Study Details

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.

Condition or Disease Intervention/Treatment Phase
  • Biological: AV7909
  • Biological: BioThrax
 Phase 2

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
168 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose:
Prevention
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 Start Date :
Jan 1, 2013
Actual Primary Completion Date :
Feb 1, 2014
Actual Study Completion Date :
Dec 1, 2014

Arms and Interventions

Arm Intervention/Treatment
Experimental: AV7909 (Day 0 and 14)

Route of administration: Intramuscular Dose: 0.5 mL Schedule: Day 0 and Day 14

Biological: AV7909
Anthrax Vaccine Adsorbed plus CPG 7909 Adjuvant
Other Names:
  • AV7909 Anthrax Vaccine
  • NuThrax

    		•
    Experimental: AV7909 (Day 0 and 28)

    Route of administration: Intramuscular Dose: 0.5 mL Schedule: Day 0 and Day 28

    Biological: AV7909
    Anthrax Vaccine Adsorbed plus CPG 7909 Adjuvant
    Other Names:
  • AV7909 Anthrax Vaccine
  • NuThrax

    		•
    Experimental: AV7909 (Day 0, 14, and 28)

    Route of administration: Intramuscular Dose: 0.5 mL Schedule: Day 0, Day 14,and Day 28

    Biological: AV7909
    Anthrax Vaccine Adsorbed plus CPG 7909 Adjuvant
    Other Names:
  • AV7909 Anthrax Vaccine
  • NuThrax

    		•
    Experimental: AV7909 Reduced Dose

    Route of administration: Intramuscular Dose: 0.25 mL Schedule: Day 0, Day 14,and Day 28

    Biological: AV7909
    Anthrax Vaccine Adsorbed plus CPG 7909 Adjuvant
    Other Names:
  • AV7909 Anthrax Vaccine
  • NuThrax

    		•
    Active Comparator: BioThrax

    Route of administration: Intramuscular Dose: 0.5 mL Schedule: Day 0, Day 14,and Day 28

    Biological: BioThrax
    Other Names:
  • Anthrax Vaccine Adsorbed (AVA)

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Toxin Neutralizing Antibody (TNA) Level at Day 63 [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

    2. Incidence of Adverse Events [From the time of the first immunization on Day 0 through Day 84]

      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

    3. 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 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

    4. Incidence of Reactogenicity By Severity [For 7 days following each vaccination on Days 0, 14, 28]

      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.

    5. Incidence of Clinical Laborabory Abnormalities [From the time of first immunization on Day 0 to Day 84]

      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.

    6. Incidence of Immunologically Significant Adverse Events of Special Interest [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 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

    1. TNA Level at Day 42 [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

    2. TNA Level at Day 28 [Day 28]

      Immunogenicity measured by the percentage of subjects with Day 28 TNA NF50 values greater than or equal to threshold

    3. TNA Seroconversion Rate [Up to Day 84]

      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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 50 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Miami Research Associates Miami Florida United States 33143
    2 Costal Carolina Research Mount Pleasant South Carolina United States 29464
    3 Central Texas Allergy and Asthma New Braunfels Texas United States 78130
    4 Jean Brown Research Salt Lake City Utah United States 84124

    Sponsors and Collaborators

    • Emergent BioSolutions
    • National Institute of Allergy and Infectious Diseases (NIAID)

    Investigators

    • Principal Investigator: Gurdyal Kalsi, MD, MTOPRA, Emergent BioSolutions

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Emergent BioSolutions
    ClinicalTrials.gov Identifier:
    NCT01770743
    Other Study ID Numbers:
    • EBS.AVA.208 / DMID 11-0055
    • HHSN272201000035C
    First Posted:
    Jan 18, 2013
    Last Update Posted:
    Feb 24, 2015
    Last Verified:
    Feb 1, 2015
    Keywords provided by Emergent BioSolutions
    post-exposure prophylaxis
    toxin neutralization assay
    Additional relevant MeSH terms:
    Anthrax
    Vaccines

    Study Results

    Participant Flow

    Recruitment Details Participants were enrolled from 16 January 2013 to 14 November 2013 at 4 medical centers in the United States.
    Pre-assignment Detail All 168 enrolled participants who met eligibility criteria were dosed.
    Arm/Group Title AV7909 (Day 0 and 14) AV7909 (Day 0 and 28) AV7909 (Day 0, 14, and 28) AV7909 Reduced Dose BioThrax
    Arm/Group Description Route of administration: Intramuscular Dose: 0.5 mL Schedule: Day 0 and Day 14 AV7909: Anthrax Vaccine Adsorbed plus CPG 7909 Adjuvant Route of administration: Intramuscular Dose: 0.5 mL Schedule: Day 0 and Day 28 AV7909: Anthrax Vaccine Adsorbed plus CPG 7909 Adjuvant Route of administration: Intramuscular Dose: 0.5 mL Schedule: Day 0, Day 14,and Day 28 AV7909: Anthrax Vaccine Adsorbed plus CPG 7909 Adjuvant Route of administration: Intramuscular Dose: 0.25 mL Schedule: Day 0, Day 14,and Day 28 AV7909: Anthrax Vaccine Adsorbed plus CPG 7909 Adjuvant Route of administration: Intramuscular Dose: 0.5 mL Schedule: Day 0, Day 14,and Day 28 BioThrax
    Period Title: Overall Study
    STARTED 44 34 23 44 23
    Treated 44 34 23 44 23
    COMPLETED 42 31 22 42 21
    NOT COMPLETED 2 3 1 2 2

    Baseline Characteristics

    Arm/Group Title AV7909 (Day 0 and 14) AV7909 (Day 0 and 28) AV7909 (Day 0, 14, and 28) AV7909 Reduced Dose BioThrax Total
    Arm/Group Description Route of administration: Intramuscular Dose: 0.5 mL Schedule: Day 0 and Day 14 AV7909: Anthrax Vaccine Adsorbed plus CPG 7909 Adjuvant Route of administration: Intramuscular Dose: 0.5 mL Schedule: Day 0 and Day 28 AV7909: Anthrax Vaccine Adsorbed plus CPG 7909 Adjuvant Route of administration: Intramuscular Dose: 0.5 mL Schedule: Day 0, Day 14,and Day 28 AV7909: Anthrax Vaccine Adsorbed plus CPG 7909 Adjuvant Route of administration: Intramuscular Dose: 0.25 mL Schedule: Day 0, Day 14,and Day 28 AV7909: Anthrax Vaccine Adsorbed plus CPG 7909 Adjuvant Route of administration: Intramuscular Dose: 0.5 mL Schedule: Day 0, Day 14,and Day 28 BioThrax Total of all reporting groups
    Overall Participants 44 34 23 44 23 168
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    33.4
    (9.0)
    32.7
    (9.7)
    29.7
    (10.2)
    32.8
    (9.2)
    32.5
    (10.4)
    32.5
    (9.5)
    Age (Count of Participants)
    <=18 years
    0
    0%
    2
    5.9%
    1
    4.3%
    0
    0%
    1
    4.3%
    4
    2.4%
    Between 18 and 65 years
    44
    100%
    32
    94.1%
    22
    95.7%
    44
    100%
    22
    95.7%
    164
    97.6%
    >=65 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Sex: Female, Male (Count of Participants)
    Female
    22
    50%
    17
    50%
    11
    47.8%
    22
    50%
    11
    47.8%
    83
    49.4%
    Male
    22
    50%
    17
    50%
    12
    52.2%
    22
    50%
    12
    52.2%
    85
    50.6%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    1
    2.3%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    0.6%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    1
    2.3%
    0
    0%
    1
    0.6%
    Black or African American
    3
    6.8%
    1
    2.9%
    3
    13%
    3
    6.8%
    2
    8.7%
    12
    7.1%
    White
    40
    90.9%
    33
    97.1%
    20
    87%
    40
    90.9%
    21
    91.3%
    154
    91.7%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    9
    20.5%
    7
    20.6%
    4
    17.4%
    5
    11.4%
    4
    17.4%
    29
    17.3%
    Not Hispanic or Latino
    35
    79.5%
    27
    79.4%
    19
    82.6%
    39
    88.6%
    19
    82.6%
    139
    82.7%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (participants) [Number]
    United States
    44
    100%
    34
    100%
    23
    100%
    44
    100%
    23
    100%
    168
    100%

    Outcome Measures

    1. Primary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Per-protocol Population at Day 63 (randomized subjects who did not have any deviation of 1) history of anthrax vaccination; 2) missing or out of window vaccination at Day 14 or 28; 3) incorrect IMP dose at one or more visits; 4) IMP dose associated with a temperature excursion; 5) prohibited medications; or 6) missing Day 63 immunogenicity data).
    Arm/Group Title AV7909 (Day 0 and 14) AV7909 (Day 0 and 28) AV7909 (Day 0, 14, and 28) AV7909 Reduced Dose BioThrax
    Arm/Group Description Route of administration: Intramuscular Dose: 0.5 mL Schedule: Day 0 and Day 14 AV7909: Anthrax Vaccine Adsorbed plus CPG 7909 Adjuvant Route of administration: Intramuscular Dose: 0.5 mL Schedule: Day 0 and Day 28 AV7909: Anthrax Vaccine Adsorbed plus CPG 7909 Adjuvant Route of administration: Intramuscular Dose: 0.5 mL Schedule: Day 0, Day 14,and Day 28 AV7909: Anthrax Vaccine Adsorbed plus CPG 7909 Adjuvant Route of administration: Intramuscular Dose: 0.25 mL Schedule: Day 0, Day 14,and Day 28 AV7909: Anthrax Vaccine Adsorbed plus CPG 7909 Adjuvant Route of administration: Intramuscular Dose: 0.5 mL Schedule: Day 0, Day 14,and Day 28 BioThrax
    Measure Participants 37 27 18 41 21
    Mean (95% Confidence Interval) [percentage of participants]
    56.8
    129.1%
    100
    294.1%
    100
    434.8%
    90.2
    205%
    52.4
    227.8%
    2. Primary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Safety Population (subjects who received at least one dose of IMP)
    Arm/Group Title AV7909 (Day 0 and 14) AV7909 (Day 0 and 28) AV7909 (Day 0, 14, and 28) AV7909 Reduced Dose BioThrax
    Arm/Group Description Route of administration: Intramuscular Dose: 0.5 mL Schedule: Day 0 and Day 14 AV7909: Anthrax Vaccine Adsorbed plus CPG 7909 Adjuvant Route of administration: Intramuscular Dose: 0.5 mL Schedule: Day 0 and Day 28 AV7909: Anthrax Vaccine Adsorbed plus CPG 7909 Adjuvant Route of administration: Intramuscular Dose: 0.5 mL Schedule: Day 0, Day 14,and Day 28 AV7909: Anthrax Vaccine Adsorbed plus CPG 7909 Adjuvant Route of administration: Intramuscular Dose: 0.25 mL Schedule: Day 0, Day 14,and Day 28 AV7909: Anthrax Vaccine Adsorbed plus CPG 7909 Adjuvant Route of administration: Intramuscular Dose: 0.5 mL Schedule: Day 0, Day 14,and Day 28 BioThrax
    Measure Participants 44 34 23 44 23
    Number [participants]
    36
    81.8%
    26
    76.5%
    17
    73.9%
    35
    79.5%
    15
    65.2%
    3. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Per-protocol Population at Day 63 (randomized subjects who did not have any deviation of 1) history of anthrax vaccination; 2) missing or out of window vaccination at Day 14 or 28; 3) incorrect IMP dose at one or more visits; 4) IMP dose associated with a temperature excursion; 5) prohibited medications; or 6) missing Day 63 immunogenicity data).
    Arm/Group Title AV7909 (Day 0 and 14) AV7909 (Day 0 and 28) AV7909 (Day 0, 14, and 28) AV7909 Reduced Dose BioThrax
    Arm/Group Description Route of administration: Intramuscular Dose: 0.5 mL Schedule: Day 0 and Day 14 AV7909: Anthrax Vaccine Adsorbed plus CPG 7909 Adjuvant Route of administration: Intramuscular Dose: 0.5 mL Schedule: Day 0 and Day 28 AV7909: Anthrax Vaccine Adsorbed plus CPG 7909 Adjuvant Route of administration: Intramuscular Dose: 0.5 mL Schedule: Day 0, Day 14,and Day 28 AV7909: Anthrax Vaccine Adsorbed plus CPG 7909 Adjuvant Route of administration: Intramuscular Dose: 0.25 mL Schedule: Day 0, Day 14,and Day 28 AV7909: Anthrax Vaccine Adsorbed plus CPG 7909 Adjuvant Route of administration: Intramuscular Dose: 0.5 mL Schedule: Day 0, Day 14,and Day 28 BioThrax
    Measure Participants 37 26 18 41 20
    Mean (95% Confidence Interval) [percentage of participants]
    86.5
    196.6%
    100
    294.1%
    94.4
    410.4%
    97.6
    221.8%
    70.0
    304.3%
    4. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Per-protocol Population at Day 63 (randomized subjects who did not have any deviation of 1) history of anthrax vaccination; 2) missing or out of window vaccination at Day 14 or 28; 3) incorrect IMP dose at one or more visits; 4) IMP dose associated with a temperature excursion; 5) prohibited medications; or 6) missing Day 63 immunogenicity data).
    Arm/Group Title AV7909 (Day 0 and 14) AV7909 (Day 0 and 28) AV7909 (Day 0, 14, and 28) AV7909 Reduced Dose BioThrax
    Arm/Group Description Route of administration: Intramuscular Dose: 0.5 mL Schedule: Day 0 and Day 14 AV7909: Anthrax Vaccine Adsorbed plus CPG 7909 Adjuvant Route of administration: Intramuscular Dose: 0.5 mL Schedule: Day 0 and Day 28 AV7909: Anthrax Vaccine Adsorbed plus CPG 7909 Adjuvant Route of administration: Intramuscular Dose: 0.5 mL Schedule: Day 0, Day 14,and Day 28 AV7909: Anthrax Vaccine Adsorbed plus CPG 7909 Adjuvant Route of administration: Intramuscular Dose: 0.25 mL Schedule: Day 0, Day 14,and Day 28 AV7909: Anthrax Vaccine Adsorbed plus CPG 7909 Adjuvant Route of administration: Intramuscular Dose: 0.5 mL Schedule: Day 0, Day 14,and Day 28 BioThrax
    Measure Participants 37 27 18 41 21
    Mean (95% Confidence Interval) [percentage of participants]
    83.8
    190.5%
    11.1
    32.6%
    94.4
    410.4%
    63.4
    144.1%
    47.6
    207%
    5. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Per-protocol Population at Day 63 (randomized subjects who did not have any deviation of 1) history of anthrax vaccination; 2) missing or out of window vaccination at Day 14 or 28; 3) incorrect IMP dose at one or more visits; 4) IMP dose associated with a temperature excursion; 5) prohibited medications; or 6) missing Day 63 immunogenicity data).
    Arm/Group Title AV7909 (Day 0 and 14) AV7909 (Day 0 and 28) AV7909 (Day 0, 14, and 28) AV7909 Reduced Dose BioThrax
    Arm/Group Description Route of administration: Intramuscular Dose: 0.5 mL Schedule: Day 0 and Day 14 AV7909: Anthrax Vaccine Adsorbed plus CPG 7909 Adjuvant Route of administration: Intramuscular Dose: 0.5 mL Schedule: Day 0 and Day 28 AV7909: Anthrax Vaccine Adsorbed plus CPG 7909 Adjuvant Route of administration: Intramuscular Dose: 0.5 mL Schedule: Day 0, Day 14,and Day 28 AV7909: Anthrax Vaccine Adsorbed plus CPG 7909 Adjuvant Route of administration: Intramuscular Dose: 0.25 mL Schedule: Day 0, Day 14,and Day 28 AV7909: Anthrax Vaccine Adsorbed plus CPG 7909 Adjuvant Route of administration: Intramuscular Dose: 0.5 mL Schedule: Day 0, Day 14,and Day 28 BioThrax
    Measure Participants 37 27 18 41 21
    Day 21
    63.9
    145.2%
    55.6
    163.5%
    77.8
    338.3%
    22.0
    50%
    14.3
    62.2%
    Day 28
    97.3
    221.1%
    40.7
    119.7%
    94.4
    410.4%
    92.7
    210.7%
    57.1
    248.3%
    Day 35
    97.1
    220.7%
    96.3
    283.2%
    100
    434.8%
    95.0
    215.9%
    66.7
    290%
    Day 42
    97.3
    221.1%
    100
    294.1%
    100
    434.8%
    100
    227.3%
    95.0
    413%
    Day 49
    91.9
    208.9%
    100
    294.1%
    100
    434.8%
    97.6
    221.8%
    95.0
    413%
    Day 63
    86.5
    196.6%
    100
    294.1%
    100
    434.8%
    97.6
    221.8%
    85.7
    372.6%
    Day 84
    75.7
    172%
    100
    294.1%
    100
    434.8%
    97.4
    221.4%
    63.2
    274.8%
    6. Primary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Safety Population (subjects who received at least one dose of IMP)
    Arm/Group Title AV7909 (Day 0 and 14) AV7909 (Day 0 and 28) AV7909 (Day 0, 14, and 28) AV7909 Reduced Dose BioThrax
    Arm/Group Description Route of administration: Intramuscular Dose: 0.5 mL Schedule: Day 0 and Day 14 AV7909: Anthrax Vaccine Adsorbed plus CPG 7909 Adjuvant Route of administration: Intramuscular Dose: 0.5 mL Schedule: Day 0 and Day 28 AV7909: Anthrax Vaccine Adsorbed plus CPG 7909 Adjuvant Route of administration: Intramuscular Dose: 0.5 mL Schedule: Day 0, Day 14,and Day 28 AV7909: Anthrax Vaccine Adsorbed plus CPG 7909 Adjuvant Route of administration: Intramuscular Dose: 0.25 mL Schedule: Day 0, Day 14,and Day 28 AV7909: Anthrax Vaccine Adsorbed plus CPG 7909 Adjuvant Route of administration: Intramuscular Dose: 0.5 mL Schedule: Day 0, Day 14,and Day 28 BioThrax
    Measure Participants 44 34 23 44 23
    Number [participants]
    2
    4.5%
    0
    0%
    0
    0%
    0
    0%
    1
    4.3%
    7. Primary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Safety Population (subjects who received at least one dose of IMP)
    Arm/Group Title AV7909 (Day 0 and 14) AV7909 (Day 0 and 28) AV7909 (Day 0, 14, and 28) AV7909 Reduced Dose BioThrax
    Arm/Group Description Route of administration: Intramuscular Dose: 0.5 mL Schedule: Day 0 and Day 14 AV7909: Anthrax Vaccine Adsorbed plus CPG 7909 Adjuvant Route of administration: Intramuscular Dose: 0.5 mL Schedule: Day 0 and Day 28 AV7909: Anthrax Vaccine Adsorbed plus CPG 7909 Adjuvant Route of administration: Intramuscular Dose: 0.5 mL Schedule: Day 0, Day 14,and Day 28 AV7909: Anthrax Vaccine Adsorbed plus CPG 7909 Adjuvant Route of administration: Intramuscular Dose: 0.25 mL Schedule: Day 0, Day 14,and Day 28 AV7909: Anthrax Vaccine Adsorbed plus CPG 7909 Adjuvant Route of administration: Intramuscular Dose: 0.5 mL Schedule: Day 0, Day 14,and Day 28 BioThrax
    Measure Participants 44 34 23 44 23
    Fatigue/Tiredness Grade 1
    11
    25%
    17
    50%
    14
    60.9%
    19
    43.2%
    8
    34.8%
    Fatigue/Tiredness Grade 2
    6
    13.6%
    5
    14.7%
    1
    4.3%
    2
    4.5%
    3
    13%
    Fatigue/Tiredness Grade 3
    3
    6.8%
    0
    0%
    1
    4.3%
    0
    0%
    0
    0%
    Muscle Ache Grade 1
    25
    56.8%
    19
    55.9%
    13
    56.5%
    27
    61.4%
    13
    56.5%
    Muscle Ache Grade 2
    6
    13.6%
    6
    17.6%
    7
    30.4%
    9
    20.5%
    3
    13%
    Muscle Ache Grade 3
    2
    4.5%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Headache Grade 1
    10
    22.7%
    15
    44.1%
    9
    39.1%
    14
    31.8%
    8
    34.8%
    Headache Grade 2
    7
    15.9%
    3
    8.8%
    6
    26.1%
    7
    15.9%
    1
    4.3%
    Headache Grade 3
    4
    9.1%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Fever Grade 1
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Fever Grade 2
    0
    0%
    1
    2.9%
    0
    0%
    0
    0%
    0
    0%
    Fever Grade 3
    2
    4.5%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Warmth Grade 1
    17
    38.6%
    15
    44.1%
    11
    47.8%
    14
    31.8%
    11
    47.8%
    Warmth Grade 2
    1
    2.3%
    0
    0%
    2
    8.7%
    2
    4.5%
    0
    0%
    Warmth Grade 3
    0
    0%
    0
    0%
    1
    4.3%
    0
    0%
    0
    0%
    Tenderness Grade 1
    31
    70.5%
    27
    79.4%
    17
    73.9%
    29
    65.9%
    14
    60.9%
    Tenderness Grade 2
    11
    25%
    6
    17.6%
    5
    21.7%
    9
    20.5%
    5
    21.7%
    Tenderness Grade 3
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Itching Grade 1
    5
    11.4%
    3
    8.8%
    3
    13%
    10
    22.7%
    5
    21.7%
    Itching Grade 2
    2
    4.5%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Itching Grade 3
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Pain Grade 1
    30
    68.2%
    29
    85.3%
    15
    65.2%
    29
    65.9%
    14
    60.9%
    Pain Grade 2
    9
    20.5%
    2
    5.9%
    7
    30.4%
    8
    18.2%
    6
    26.1%
    Pain Grade 3
    1
    2.3%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Arm Motion Limitation Grade 1
    21
    47.7%
    15
    44.1%
    11
    47.8%
    17
    38.6%
    8
    34.8%
    Arm Motion Limitation Grade 2
    11
    25%
    9
    26.5%
    7
    30.4%
    11
    25%
    5
    21.7%
    Arm Motion Limitation Grade 3
    1
    2.3%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Redness Grade 1
    6
    13.6%
    5
    14.7%
    3
    13%
    10
    22.7%
    8
    34.8%
    Redness Grade 2
    2
    4.5%
    1
    2.9%
    1
    4.3%
    1
    2.3%
    0
    0%
    Redness Grade 3
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Lump Grade 1
    13
    29.5%
    6
    17.6%
    9
    39.1%
    16
    36.4%
    10
    43.5%
    Lump Grade 2
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Lump Grade 3
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Swelling Grade 1
    12
    27.3%
    7
    20.6%
    7
    30.4%
    14
    31.8%
    7
    30.4%
    Swelling Grade 2
    0
    0%
    0
    0%
    2
    8.7%
    0
    0%
    1
    4.3%
    Swelling Grade 3
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Bruise Grade 1
    4
    9.1%
    6
    17.6%
    2
    8.7%
    8
    18.2%
    4
    17.4%
    Bruise Grade 2
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Bruise Grade 3
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    8. Primary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Safety Population (subjects who received at least one dose of IMP)
    Arm/Group Title AV7909 (Day 0 and 14) AV7909 (Day 0 and 28) AV7909 (Day 0, 14, and 28) AV7909 Reduced Dose BioThrax
    Arm/Group Description Route of administration: Intramuscular Dose: 0.5 mL Schedule: Day 0 and Day 14 AV7909: Anthrax Vaccine Adsorbed plus CPG 7909 Adjuvant Route of administration: Intramuscular Dose: 0.5 mL Schedule: Day 0 and Day 28 AV7909: Anthrax Vaccine Adsorbed plus CPG 7909 Adjuvant Route of administration: Intramuscular Dose: 0.5 mL Schedule: Day 0, Day 14,and Day 28 AV7909: Anthrax Vaccine Adsorbed plus CPG 7909 Adjuvant Route of administration: Intramuscular Dose: 0.25 mL Schedule: Day 0, Day 14,and Day 28 AV7909: Anthrax Vaccine Adsorbed plus CPG 7909 Adjuvant Route of administration: Intramuscular Dose: 0.5 mL Schedule: Day 0, Day 14,and Day 28 BioThrax
    Measure Participants 44 34 23 44 23
    Hemoglobin
    39
    88.6%
    29
    85.3%
    20
    87%
    42
    95.5%
    19
    82.6%
    Leukocytes
    8
    18.2%
    4
    11.8%
    3
    13%
    3
    6.8%
    0
    0%
    Neutrophils
    2
    4.5%
    1
    2.9%
    1
    4.3%
    3
    6.8%
    0
    0%
    Lymphocytes
    0
    0%
    1
    2.9%
    4
    17.4%
    2
    4.5%
    0
    0%
    Aspartate Aminotransferase
    3
    6.8%
    2
    5.9%
    3
    13%
    4
    9.1%
    1
    4.3%
    Alanine Aminotransferase
    2
    4.5%
    3
    8.8%
    1
    4.3%
    3
    6.8%
    2
    8.7%
    Glucose
    9
    20.5%
    7
    20.6%
    8
    34.8%
    13
    29.5%
    2
    8.7%
    Glucose Fasting
    0
    0%
    0
    0%
    1
    4.3%
    0
    0%
    0
    0%
    Bilirubin
    1
    2.3%
    2
    5.9%
    1
    4.3%
    0
    0%
    1
    4.3%
    Blood Urea Nitrogen
    1
    2.3%
    0
    0%
    1
    4.3%
    1
    2.3%
    0
    0%
    Urine Glucose
    2
    4.5%
    1
    2.9%
    0
    0%
    0
    0%
    1
    4.3%
    Urine Protein
    16
    36.4%
    10
    29.4%
    5
    21.7%
    13
    29.5%
    6
    26.1%
    Urine Erythrocytes
    11
    25%
    5
    14.7%
    4
    17.4%
    7
    15.9%
    8
    34.8%
    9. Primary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Safety Population (subjects who received at least one dose of IMP)
    Arm/Group Title AV7909 (Day 0 and 14) AV7909 (Day 0 and 28) AV7909 (Day 0, 14, and 28) AV7909 Reduced Dose BioThrax
    Arm/Group Description Route of administration: Intramuscular Dose: 0.5 mL Schedule: Day 0 and Day 14 AV7909: Anthrax Vaccine Adsorbed plus CPG 7909 Adjuvant Route of administration: Intramuscular Dose: 0.5 mL Schedule: Day 0 and Day 28 AV7909: Anthrax Vaccine Adsorbed plus CPG 7909 Adjuvant Route of administration: Intramuscular Dose: 0.5 mL Schedule: Day 0, Day 14,and Day 28 AV7909: Anthrax Vaccine Adsorbed plus CPG 7909 Adjuvant Route of administration: Intramuscular Dose: 0.25 mL Schedule: Day 0, Day 14,and Day 28 AV7909: Anthrax Vaccine Adsorbed plus CPG 7909 Adjuvant Route of administration: Intramuscular Dose: 0.5 mL Schedule: Day 0, Day 14,and Day 28 BioThrax
    Measure Participants 44 34 23 44 23
    Number [participants]
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%

    Adverse Events

    Time Frame From signing of the ICF to the first immunization on Day 0 (AEs recorded only if resulting from a study-related procedure) then through Day 84.
    Adverse Event Reporting Description AEs were collected at study visits on Days 0, 7, 14, 21, 28, 35, 42, 49, 63, and 84, and at the early withdrawal visit. The occurrence of SAEs and adverse events of special interest (autoimmune-related) were collected at safety follow-up phone contacts at 6 and 12 months following the last scheduled vaccination.
    Arm/Group Title AV7909 (Day 0 and 14) AV7909 (Day 0 and 28) AV7909 (Day 0, 14, and 28) AV7909 Reduced Dose BioThrax
    Arm/Group Description Route of administration: Intramuscular Dose: 0.5 mL Schedule: Day 0 and Day 14 AV7909: Anthrax Vaccine Adsorbed plus CPG 7909 Adjuvant Route of administration: Intramuscular Dose: 0.5 mL Schedule: Day 0 and Day 28 AV7909: Anthrax Vaccine Adsorbed plus CPG 7909 Adjuvant Route of administration: Intramuscular Dose: 0.5 mL Schedule: Day 0, Day 14,and Day 28 AV7909: Anthrax Vaccine Adsorbed plus CPG 7909 Adjuvant Route of administration: Intramuscular Dose: 0.25 mL Schedule: Day 0, Day 14,and Day 28 AV7909: Anthrax Vaccine Adsorbed plus CPG 7909 Adjuvant Route of administration: Intramuscular Dose: 0.5 mL Schedule: Day 0, Day 14,and Day 28 BioThrax
    All Cause Mortality
    AV7909 (Day 0 and 14) AV7909 (Day 0 and 28) AV7909 (Day 0, 14, and 28) AV7909 Reduced Dose BioThrax
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    AV7909 (Day 0 and 14) AV7909 (Day 0 and 28) AV7909 (Day 0, 14, and 28) AV7909 Reduced Dose BioThrax
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 2/44 (4.5%) 0/34 (0%) 0/23 (0%) 0/44 (0%) 1/23 (4.3%)
    Infections and infestations
    Cellulitis 1/44 (2.3%) 1 0/34 (0%) 0 0/23 (0%) 0 0/44 (0%) 0 0/23 (0%) 0
    Pyelonephritis 0/44 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/44 (0%) 0 1/23 (4.3%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Rectal neoplasm 1/44 (2.3%) 1 0/34 (0%) 0 0/23 (0%) 0 0/44 (0%) 0 0/23 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Atelectasis neonatal 1/44 (2.3%) 1 0/34 (0%) 0 0/23 (0%) 0 0/44 (0%) 0 0/23 (0%) 0
    Other (Not Including Serious) Adverse Events
    AV7909 (Day 0 and 14) AV7909 (Day 0 and 28) AV7909 (Day 0, 14, and 28) AV7909 Reduced Dose BioThrax
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 32/44 (72.7%) 18/34 (52.9%) 10/23 (43.5%) 27/44 (61.4%) 9/23 (39.1%)
    Cardiac disorders
    Bradycardia 2/44 (4.5%) 2 0/34 (0%) 0 1/23 (4.3%) 1 5/44 (11.4%) 7 0/23 (0%) 0
    Infections and infestations
    Nasopharyngitis 7/44 (15.9%) 7 3/34 (8.8%) 3 0/23 (0%) 0 2/44 (4.5%) 2 1/23 (4.3%) 1
    Upper respiratory tract infection 10/44 (22.7%) 10 5/34 (14.7%) 5 2/23 (8.7%) 2 7/44 (15.9%) 8 2/23 (8.7%) 2
    Urinary tract infection 0/44 (0%) 0 1/34 (2.9%) 1 2/23 (8.7%) 2 1/44 (2.3%) 1 0/23 (0%) 0
    Viral infection 1/44 (2.3%) 1 2/34 (5.9%) 3 0/23 (0%) 0 2/44 (4.5%) 2 0/23 (0%) 0
    Vulvovaginal mycotic infection 0/22 (0%) 0 0/17 (0%) 0 0/11 (0%) 0 0/22 (0%) 0 2/11 (18.2%) 2
    Investigations
    AST increased 2/44 (4.5%) 2 2/34 (5.9%) 3 1/23 (4.3%) 1 1/44 (2.3%) 1 0/23 (0%) 0
    Blood pressure diastolic decreased 5/44 (11.4%) 5 3/34 (8.8%) 4 2/23 (8.7%) 2 6/44 (13.6%) 10 0/23 (0%) 0
    Blood pressure increased 3/44 (6.8%) 4 0/34 (0%) 0 0/23 (0%) 0 0/44 (0%) 0 0/23 (0%) 0
    Heart rate decreased 1/44 (2.3%) 2 4/34 (11.8%) 6 0/23 (0%) 0 1/44 (2.3%) 1 2/23 (8.7%) 2
    Protein urine present 0/44 (0%) 0 0/34 (0%) 0 0/23 (0%) 0 0/44 (0%) 0 2/23 (8.7%) 2
    Red blood cells urine positive 2/44 (4.5%) 3 0/34 (0%) 0 0/23 (0%) 0 0/44 (0%) 0 4/23 (17.4%) 5
    Respiratory rate increased 6/44 (13.6%) 14 2/34 (5.9%) 4 4/23 (17.4%) 9 10/44 (22.7%) 13 2/23 (8.7%) 2
    Musculoskeletal and connective tissue disorders
    Back pain 2/44 (4.5%) 2 2/34 (5.9%) 2 0/23 (0%) 0 2/44 (4.5%) 2 0/23 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Oropharyngeal pain 1/44 (2.3%) 1 2/34 (5.9%) 2 1/23 (4.3%) 1 2/44 (4.5%) 2 0/23 (0%) 0
    Pharyngeal erythema 0/44 (0%) 0 0/34 (0%) 0 2/23 (8.7%) 2 0/44 (0%) 0 0/23 (0%) 0

    Limitations/Caveats

    A few events collected in e-diary were downgraded (severe to moderate) on verification by the PI but were unable to be corrected in subjects' e-diary data: headache & fatigue/tenderness in 2 subjects each; muscle ache & pain & AML in 1 subject each.

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Sponsor is responsible for public disclosure of study data. Any proposed publication is subject to review agreed between the Division of Microbiology and Infectious Diseases (DMID) and Emergent; between Emergent and the contract research organizations (CROs)/vendors; and between the CROs and the site Principal Investigator. Data are the property of the sponsor and cannot be published without prior authorization from the sponsor, but data and publication thereof will not be unduly withheld.

    Results Point of Contact

    Name/Title Dr. Gurdyal Kalsi
    Organization Emergent BioSolutions
    Phone 301-216-9927
    Email kalsig@ebsi.com
    Responsible Party:
    Emergent BioSolutions
    ClinicalTrials.gov Identifier:
    NCT01770743
    Other Study ID Numbers:
    • EBS.AVA.208 / DMID 11-0055
    • HHSN272201000035C
    First Posted:
    Jan 18, 2013
    Last Update Posted:
    Feb 24, 2015
    Last Verified:
    Feb 1, 2015